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Influence of lifestyle modification on arterial stiffness and wave reflections
AJH
2005; 18:137–144
Influence of Lifestyle Modification on Arterial Stiffness and Wave Reflections Hirofumi Tanaka and Michel E. Safar Arterial stiffness and wave reflections exert a number of adverse effects on cardiovascular function and disease risk and are associated with a greater rate of mortality in patients with end-stage renal failure and essential hypertension. Accordingly, the prevention and treatment of arterial stiffness are of paramount importance. Because arterial stiffening is being recognized as a critical precursor of cardiovascular disease (CVD), it is essential to understand the role of lifestyle modifications on preventing and reversing arterial stiffening. Available evidence indicates that lifestyle modifications, in particular aerobic exercise and sodium restriction, appear to be clinically
efficacious therapeutic interventions for preventing and treating arterial stiffening. Thus, sufficient evidence is available to recommend lifestyle modifications as part of a first-line therapeutic approach for arterial stiffening. However, more information is needed for a full understanding and optimal use of lifestyle modifications in the management of arterial stiffening. Am J Hypertens 2005;18: 137–144 © 2005 American Journal of Hypertension, Ltd.
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modifications, and smoking cessation. Much of the confusion in the field of arterial stiffness arises from the different terminologies and methodologies used to express the elastic properties of an artery.3 In this review, we specified the methodology used in each study so that readers can assess each study with their own judgments. Interested readers may refer to a recent consensus report that reviewed various methodologies to assess arterial stiffness.3
Key Words: Nonpharmacological, arterial compliance, exercise, sodium restriction.
arge elastic arteries expand and recoil with cardiac pulsation and relaxation. During systole, a significant portion of the ejected stroke volume is stored by arterial distention, which acts to buffer the rise in systolic pressure and to convert pulsatile cardiac ejection into continuous blood flow in capillary beds. Reductions in arterial compliance and increases in arterial stiffness are believed to contribute to the pathophysiology of cardiovascular disease (CVD) and have recently been identified as powerful and independent risk factors for CVD.1,2 Increased arterial stiffness can contribute to the development and progression of hypertension, left ventricular hypertrophy, myocardial infarction, and congestive heart failure.1 For most risk factors for CVD, the first-line approach for prevention and treatment for development of CVD is lifestyle modification (Fig. 1). Given the role of arterial stiffness as a critical precursor of CVD,2 it is important to recognize the effects of lifestyle modifications for the prevention and treatment of arterial stiffening. An emerging body of evidence supports the concept that lifestyle modifications can prevent and reverse arterial stiffening. This article reviews the evidence regarding the influence of lifestyle modifications on arterial stiffening and wave reflections. The focus will be placed on increased physical activity, weight loss, a reduced salt intake, other dietary
A cross-sectional study from the Baltimore Longitudinal Study of Aging found that older men who performed endurance exercise on a regular basis demonstrated lower levels of aortic pulse wave velocity (PWV) and carotid augmentation index (AI; an indicator of the magnitude of arterial wave reflection and arterial stiffness) than did their sedentary peers.4 We also reported that significant agerelated increases in central arterial stiffness (aortic PWV and carotid augmentation index) were absent in physically active postmenopausal women and that aerobic fitness was strongly associated with arterial stiffness.5 Physically active individuals often demonstrate resting bradycardia, which could act on wave reflections and pulse pressure
Received June 4, 2004. First decision July 12, 2004. Accepted July 13, 2004. From the Department of Kinesiology and Health Education (HT), University of Texas, Austin, Texas; and Centre de Diagnostic (MES), Hôpital Hôtel Dieu, Paris, France.
Research supported by National Institutes of Health grants AG00847 and AG020966. Address correspondence and reprint requests to Dr. Hirofumi Tanaka, Department of Kinesiology and Health Education, University of Texas, Austin, TX 78712; e-mail: [email protected]
© 2005 by the American Journal of Hypertension, Ltd. Published by Elsevier Inc.
Regular Exercise Aerobic (Endurance) Exercise
0895-7061/05/$30.00 doi:10.1016/j.amjhyper.2004.07.008
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FIG. 1 Processes of arterial stiffening and destiffening. AGEs ⫽ advanced glycation end-products.
amplifications.6 However, there are no consistent associations between resting heart rate and arterial stiffness in these studies involving endurance-trained adults.5,7,8 In contrast to the effects on central elastic artery, peripheral arterial stiffness (leg PWV and arm PWV) was not different between sedentary and physically active adults.5 These cross-sectional findings provide support for the role of regular aerobic exercise in the primary prevention of central arterial stiffening and wave reflections. However, athletic and sedentary adults may differ in terms of many constitutional factors. To demonstrate the direct effect of regular exercise on arterial stiffness, interventional studies are required. Unknown to most, the first intervention study to determine the influence of exercise training on arterial stiffness was conducted in Japan. After 9 months of physical training incorporating a variety of exercises including jogging, soccer, handball, and judo, Ikegami et al9 found a small but significant reduction in aortic PWV in 80 healthy young Japanese men. We recently completed an exercise intervention study involving previously sedentary but healthy middle-aged and older men, and reported that a relatively brief period (3 months) of aerobic exercise can increase carotid arterial compliance as measured with a simultaneous application of high-resolution ultrasound and applanation tonometry (Fig. 2).8 This improvement was not associated with changes in body weight, adiposity, blood pressure (BP), plasma cholesterol, or resting heart rate, indicating a direct effect of exercise on arterial compliance. Importantly, this was accomplished with an intensity (moderate) and type (walking) of physical activity that
can be performed by most, if not all, healthy older adults.8 In contrast to central elastic arteries, the compliance of the peripheral muscular artery did not change with exercise training,8 indicating that the effect of resistance training involves only central elastic arteries, which have a cushioning function that dampens fluctuations in pressure and flow. Because the effects of exercise training were observed only on the central elastic artery (carotid artery) but not on the peripheral muscular artery (ie, femoral artery), it is possible to hypothesize that some mechanical/physical (local) factors may have interacted with structural or functional mechanisms to improve arterial compliance. We recently prescribed an identical aerobic exercise program
Arterial Compliance (mm2/mmHg) 0.20
* 0.15 1.5±0.2 1.2±0.1
0.10
0.05 Before Training
After Training
FIG. 2 Carotid arterial compliance before and after 3 months of aerobic exercise intervention.8
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to middle-aged and older women and found that women appear to benefit from regular aerobic exercise to a greater extent than do men (40% v 25%).7 Taken together, these results suggest that habitual aerobic exercise may be an effective lifestyle intervention for augmenting central arterial compliance in healthy adults. Available evidence indicates that short-term aerobic exercise intervention may not be as effective in reducing arterial stiffness in a patient population as in healthy adults. For example, we recently reported that 3 months of exercise intervention produced only small reductions in aortic PWV and augmentation index in postmenopausal women with elevated systolic BP.10 In another study, short-term aerobic exercise training was unable to increase systemic arterial compliance in patients with isolated systolic hypertension.11 It is possible that the plasticity of the arterial function to adapt to exercise training may diminish as arteries are exposed to chronically elevated BP. Because hypertensive patients are arguably the greatest beneficiaries of destiffening therapy, larger scale studies are warranted to investigate the potential efficacy of long-term aerobic exercise intervention on arterial stiffness in this population. Resistance (Weight) Training In recent years, statements on physical activity by various health organizations have recommended weight training as part of a preventive and rehabilitative program of physical activity.12 These recommendations are based primarily on the documented impact of weight training on the attenuation of osteoporosis and sarcopenia as well as on the emerging beneficial effects on metabolic risk factors. Given this, it is reasonable to hypothesize that weight training would be associated with reduced arterial stiffness. However, the currently available evidence does not support this.13,14 In our recent study,13 sedentary and resistance-trained men were carefully matched for age, height, BP, heart rate, and metabolic risk factors to isolate the influence of resistance training as much as possible. Additionally, in an attempt to isolate the effect of longterm resistance training per se, we excluded those who had been concurrently performing endurance training and those taking anabolic steroids or other performance enhancing drugs. However, middle-aged men who performed resistance training on a regular basis demonstrated greater levels of arterial stiffness compared with their sedentary peers.13 It is possible that the marked elevations in arterial BP, as high as 320/250 mm Hg,15 during weight lifting, may result in long-term increases in the smooth muscle content of the arterial wall and the load-bearing properties of collagen and elastin, thereby increasing arterial stiffness. Indeed, carotid arterial compliance was modestly but significantly associated with carotid wall thickness. Given the well known limitation of cross-sectional study design and the conflicting results between aerobic and strength training, these cross-sectional study
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findings should be confirmed prospectively with the interventional approach.
Weight Reduction Obesity is a major public health problem with markedly increased morbidity and mortality risks from nearly all of the common CVD. In particular, obesity is closely linked with the development of hypertension.16 Several studies have investigated the relation between obesity and large arterial functions with contradictory results. In some studies, obese subjects have been found to have higher degrees of arterial stiffness,17,18 and in other studies lower degrees.19,20 These discordant results may be due to the method used to describe mechanical wall properties of arteries. For example, obese subjects are expected to have larger stroke volume and cardiac output simply because of the larger body size, and this could influence some measures of arterial distensibility (such as systemic arterial compliance and stroke volume/pulse pressure ratio) that rely on stroke volume. These methodologic artifacts could explain, at least in part, the paradoxically smaller degree of arterial stiffness reported in obese subjects. Similarly, the estimation of arterial length required for the PWV measurements may not be accurate in obese individuals. Moreover, arterial compliance measurements using ultrasonography may be limited by decreased acoustic penetration and its dependence on lumen diameter, which tends to be greater in obese individuals. Studies using the measures of arterial stiffness that are relatively free of these methodologic issues (eg, MRI) have consistently demonstrated that obese as well as overweight individuals have increased levels of arterial stiffness17,21 and that measures of adiposity are closely and positively associated with arterial stiffness.18,21 Interestingly, a recent study reported that brachial artery distensibility was associated with fasting serum leptin concentration.22 Because obesity is closely associated with the development of insulin resistance and the metabolic syndrome, it is not surprising that arterial stiffness is found to be increased in these disease states.23 Few interventional studies have investigated the effects of weight loss on arterial stiffness, and most of them are short-term studies lasting between 4 and 16 weeks.21,24,25 In one of the first studies to address this, a group of investigators from Paris reported that 4 weeks of caloric restriction, which aimed to achieve a 10% to 15% reduction in body weight, induced significant reductions in BP and aortic PWV in nine obese hypertensive subjects.21 Moreover, in normotensive obese men, 3 months on an energy-restricted diet induced a significant reduction in body weight, which was associated with reductions in large artery stiffness.25 The improvement in the elastic properties of arteries observed in this study, however, appears to be dependent on the accompanied reductions in arterial BP, because no change in arterial stiffness was observed when it was measured under isobaric condi-
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tions.25 In obese women, a 16-week weight loss program achieved ⬃10% reduction in body weight and induced ⬃30% increase in systemic arterial compliance.24 The increase in arterial compliance was significantly but modestly associated with the reduction in BP, suggesting that the effect of weight reduction on arterial distensibility may be mediated indirectly by the concomitant decreases in BP. However, there was a subgroup of women who achieved significant reductions in arterial stiffness without any changes in arterial BP.24 Thus, the available evidence indicates that weight reduction may decrease arterial stiffness in obese subjects. However, currently it is not clear whether the reduction in arterial stiffness is due to weight reduction per se or whether it is an epiphenomenon of BP reductions accompanying weight loss. The direct effects of weight reduction on arterial stiffness should be investigated in the future in obese subjects in general and in obese hypertensive subjects in particular.
Dietary Modifications There is now overwhelming evidence that dietary factors influence the risk of cardiovascular disease, and emerging data indicate that arterial stiffness is markedly influenced by dietary factors. Red wine containing alcohol induced small but significant reductions in BP, PWV, and AI obtained at the radial artery.26 These effects were not observed when dealcoholized wine was consumed. Although part of the effect of alcohol appears to be BP dependent, the reduction in arterial stiffness remained significant even after adjusting for BP changes.26 Recent studies indicate that caffeine intake, in the form of a tablet27 or in coffee,28 produces a short-term increase in AI obtained at the radial artery in normotensive27 and hypertensive28 subjects. No such changes were seen with placebo27 or decaffeinated coffee intake.28 Taken together, these studies suggest that arterial stiffness can be changed acutely with commonly consumed dietary factors. Sodium Restriction Salt intake is being recognized as an important factor determining the BP differences between and within populations and is a major cause of the rise in arterial BP with advancing age.29 Increased salt intake is thought to raise BP by increasing plasma volume, blood volume, and subsequently cardiac output. Although this could be true in short-term experiments involving saline infusion,30 the evidence that the chronic increase in cardiac output is responsible for salt-induced increase in BP is not convincing,31 because increased blood volume is associated with increased venous compliance with little change in central venous pressure and cardiac output. Alternatively, there is increasing evidence supporting the link between sodium intake and arterial stiffness. The INTERSALT Study indicates that excess intake of sodium, as reflected in 24-h urinary sodium excretion, is associated with an increase in systolic BP but not in diastolic BP.29 Additionally, aortic
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FIG. 3 Carotid arterial compliance at baseline, in each of 4 weeks of the low sodium condition, and during the 4 weeks of the normal sodium condition.37
PWV was measured in groups of individuals living in a rural or an urban community in China.32 Aortic PWV was significantly lower in the rural community with low salt intake, and the group difference persisted even when subgroups of subjects with the same BP and age were compared.32 Cross-sectional findings in normotensive adults varying in age indicate that subjects who follow a diet low in sodium demonstrate lower levels of PWV than age- and BP-matched controls with higher salt intake.33 Moreover, borderline hypertensive subjects who are sodium sensitive with regard to BP have decreased arterial distensibility compared with sodium-resistant subjects.34 Plasma volume, cardiac output, and BP were not different between sodium-sensitive and sodium-resistant subjects and could not have been responsible for observed differences in arterial stiffness.34 Taken together, these cross-sectional findings support the hypothesis that sodium intake influences arterial stiffness long term, independent of BP. There have been only a few intervention studies that determined the effects of salt restriction on arterial stiffness.10,35,36 We reported that in postmenopausal women with elevated BP, 3 months of moderate dietary sodium restriction reduced both casual and 24-h BP.10 The changes in resting and 24-h systolic BP and pulse pressure were consistently correlated with the corresponding changes in both aortic PWV and carotid AI. Importantly, the reductions in carotid AI were not associated with changes in body weight, mean BP, plasma volume, and heart rate,10 indicating a direct effect of sodium restriction on arterial stiffness. An interesting observation in this study is that sodium restriction was more efficacious in reducing BP and arterial stiffness than a moderate aerobic exercise program in postmenopausal women.10 We recently followed-up this previous study using carotid arterial compliance measured with a simultaneous application of ultrasonography and applanation tonometry.37 A novel finding of this study is that arterial compliance increased very rapidly at the end of week 1 of sodium restriction, attaining peak levels by week 2 (Fig. 3).
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Other Dietary Modifications To date, a number of short-term dietary modifications have been shown to change the elastic properties of large arteries, although most studies have involved a relatively small number of subjects. A comparison of aortic PWV between inhabitants of fishing and farming villages in Japan revealed that the population with higher fish consumption demonstrated lower arterial stiffness.38 In an Australian cross-sectional study involving both healthy and diabetic subjects, fish eaters demonstrated a greater arterial compliance compared with non–fish eaters who were matched for age, BMI, and BP.39 These cross-sectional study findings were confirmed by interventional studies. In placebo-controlled studies, several weeks of fish oil supplementation with n-3 fatty acid significantly improved arterial wall characteristics in obese subjects40 as well as in diabetic subjects.41 Collectively, these findings are consistent with the hypothesis that fish oils, more specifically n-3 fatty acids, may reduce arterial stiffness. The antioxidant vitamins, in particular ascorbic acid and ␣-tocopherol, have been reported to reduce arterial stiffness. In a placebo-controlled, double-blind, randomized study, AI measured at the radial artery was reduced 6 h after oral intake of vitamin C in healthy subjects.42 The results of this short-term study are in agreement with a recent intervention study involving diabetic patients.43 After 4 weeks of oral intake of ascorbic acid, aortic AI estimated from the radial artery waveform decreased significantly.43 It should be noted, however, that reductions in peripheral resistance, which could be induced by vitamin C intake, may be responsible for the reduction in AI. Similarly, 8 weeks of vitamin E intake induced 44% increase in systemic arterial compliance in middle-aged men and women.44 These results suggest that the antioxidant vitamin may be beneficial in reversing arterial stiffening, presumably through its effect as free radical scavenger. Although the available data regarding the effects of vitamins on arterial stiffness are encouraging, there appears to be little evidence that supplements of vitamin C or E are sufficiently effective in preventing and controlling high BP or cardiovascular disease (that is, sequelae of arterial stiffening).45,46 Thus, the clinical significance of the short-term effects of vitamins on arterial stiffness remains to be determined. In fact, a recent wellcontrolled study involving both short-term and long-term administration of ascorbic acid failed to affect carotid arterial compliance in healthy young and older men.47 Similarly, homocysteine lowering therapy with folic acidbased treatments have been shown to be ineffective in improving carotid artery compliance.48 Thus, available information is not encouraging in terms of recommending antioxidant vitamins for the prevention and treatment of arterial stiffening and subsequent CVD. Smoking Cessation Smoking is a major and independent risk factor for development and progression of cardiovascular disease. Despite
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the strong evidence linking cigarette smoking and cardiovascular disease, the mechanisms by which smoking causes cardiovascular disease remain poorly understood. In addition to smoking-induced endothelial dysfunction, emerging evidence indicates that smoking may exert its effects, at least in part, through decreasing arterial compliance. Short-term cigarette smoking was found to increase arterial stiffness in nonsmokers49,50 and smokers,49,51,52 and the magnitude of increases in arterial stiffness after smoking was similar between the two groups.49 The greatest effects of short-term smoking on arterial stiffness seem to occur in the first 5 minutes after smoking,49,53 and ambulatory BP measurements indicate that smoking increases pulse pressure during day but not at night (that is, when subjects do not smoke).54 A recent study has demonstrated that “passive” or environmental smoking is also associated with acute deterioration in the elastic properties of the aorta.52 Consistent with the short-term effects of smoking, the majority of studies to date have reported that long-term smoking is associated with arterial stiffening,55,56 although there are some conflicting reports.57 The effects of longterm smoking on arterial stiffness have been observed both in normotensive and hypertensive individuals55,56 and appear to be independent of BP levels.56 Long-term exposure to environmental tobacco smoke (ie, passive smoking) also is associated with carotid arterial stiffening in a dosedependent manner.58 These results indicate that some chemicals in the gas may be a cause of smoking-induced arterial stiffening. In this context, exposure to oxidizing gases may be a primary suspect, as blood levels of nicotine and carbon monoxide are quite low in passive smokers59 who also demonstrate arterial stiffening. To the best of our knowledge, there has been no study to determine directly whether smoking cessation would reduce stiffnness in large elastic arteries. However, because several weeks of smoking cessation reduces systolic BP in hypertensive patients,60 it is reasonable to hypothesize that arterial stiffness would be reduced with smoking cessation. Nonetheless, the information regarding the influence of smoking cessation on arterial stiffness should be derived in future studies.
Physiological Mechanisms Underlying Arterial Destiffening The three primary elements of the arterial wall that determine its stiffness are as follows: 1) the amount/proportion of elastin and collagen (quantitative structural elements); 2) fracture/fragmentation of elastic lamellae and the crosslinking of collagen and advanced glycation end-products (qualitative structural elements); and 3) the vasoconstrictor tone exerted by its smooth muscle cells (functional elements) (Fig. 1). Although different lifestyle modifications would likely act on different physiologic mechanisms to change arterial stiffness, any favorable influences of lifestyle modifications should involve an attenuation or
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reversal of one or more of the mechanisms contributing to arterial stiffening. It is thought that structural changes, in particular elastin and collagen content, play a major role in determining central arterial stiffness. However, the elastin– collagen composition of the arterial wall represents a more longterm component of the stiffness of the artery and changes only over a period of years.61 As such, it is unlikely that this may be a physiologic mechanism underlying reductions in arterial stiffness induced by short-term lifestyle modifications described above. In fact, in an animal experiment, we recently demonstrated that the influence of regular aerobic exercise on arterial stiffness does not appear to be mediated by the quantitative changes in arterial wall elastin and collagen.62 In addition to the “quantitative” changes, the constituents of arterial wall undergo “qualitative” changes with age, hypertension, and diabetes (for example, fracture and fragmentation of elastic lamellae as well as changes and remodeling of extracellular matrix, including fibronectin and integrin).63,64 In particular, there is an accumulation of additional interstitial collagen in the arterial wall,63 which can react nonenzymatically with glucose, link them together, and produce advanced glycation end-products.63 These end-products accumulate slowly on long-lived proteins to stiffen arteries.63 It is plausible to hypothesize that some lifestyle interventions, such as exercise, may act to break these links to reduce arterial stiffness. In this context, the agents that break these protein cross-links reduce arterial stiffness in aged monkeys65 as well as in aged adults.66 Because this favorable effect can be induced in several weeks,65,66 it is reasonable to hypothesize that some lifestyle modifications may act on arterial stiffness via this mechanism. In marked contrast to the prevailing thought that arterial stiffness is a relatively static measure, arterial stiffness has a large “reserve” and can be altered— even acutely— over a much shorter period.67,68 The ability to modify arterial stiffness over the short term is thought to be due to modulation of the contractile states of the vascular smooth muscle cells in the arterial wall.67,68 As such, it is possible that the reduction in vasoconstrictor tone exerted by smooth muscle cells may be a potential mechanism underlying improvements in arterial stiffness with lifestyle modifications. Another related and plausible mechanism contributing to the reduction in arterial stiffness is reduced vascular endothelium mediated vasodilator tone. The augmented nitric oxide bioavailability should tonically suppress vascular smooth muscle cell tone, thereby reducing arterial stiffness. In this context, nitric oxide was recently shown to regulate brachial artery elasticity in humans.69
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crease in systolic BP, which acts to reverse cardiac hypertrophy, and an increase in diastolic BP, which improves coronary circulation, treatments that reduce pulse pressure and arterial stiffness may further reduce cardiovascular risks. It is a matter of debate as to whether a direct measurement of arterial stiffness would provide a greater increment in cardiovascular risk stratification over an indirect index, including systolic and pulse pressure.70 However, systolic and pulse pressure lose their predictive power for cardiovascular events after adjustment for arterial stiffness, and arterial stiffness exerts the stronger independent predictive power.71 As such, arterial stiffness should be considered as a marker of cardiovascular risk independent of brachial BP levels. Current guidelines recommend that to prevent and treat most cardiovascular risk factors, lifestyle modifications be used for an initial period of 3 to 6 months, followed by pharmacological intervention if necessary to achieve normalization. Available evidence indicates that lifestyle modifications—in particular, aerobic exercise and sodium restriction—appear to be clinically efficacious therapeutic interventions for preventing and treating arterial stiffening. Thus, sufficient evidence is available to recommend lifestyle modifications as part of a first-line therapeutic approach for arterial stiffening. However, more information is needed for a more complete understanding and optimal use of lifestyle modifications in the management of arterial stiffening.
References 1.
2.
3.
4.
5.
6.
7.
Perspectives Arterial stiffening and increased pulse pressure are being recognized as predictors of CVD, in particular myocardial infarction. Because reduced pulse pressure involves a de-
8.
Safar ME, London GM: Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. The Clinical Committee of Arterial Structure and Function. J Hypertens 2000;18:1527–1535. Hodes RJ, Lakatta EG, McNeil CT: Another modifiable risk factor for cardiovascular disease? Some evidence points to arterial stiffness. J Am Geriatr Soc 1995;43:581–582. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE: Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens 2002;15:426 – 444. Vaitkevicious PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, Yin FCP, Lakatta EG: Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 1993;88: 1456 –1462. Tanaka H, DeSouza CA, Seals DR: Absence of age-related increase in central arterial stiffness in physically active women. Arterioscler Thromb Vasc Biol 1998;18:127–132. Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ: The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol (Lond) 2000;525:263– 270. Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H: Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res 2003;57:861– 868. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR: Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000;102:1270 –1275.
AJH–January 2005–VOL. 18, NO. 1
9.
10.
11.
12.
13.
14.
15.
16. 17.
18.
19. 20.
21.
22.
23.
24.
25.
Ikegami H, Satake M, Kurokawa T, Tan N, Sugiura T, Yamazaki Y: Effects of physical training on body composition, respiro-circulatory functions, blood constituents, and physical abilities. Part 1: men aged 30 years. J Phys Fitness Japan 1983;32:302–309. Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, Hiatt WR, Davy KP, DeSouza CA: Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. J Am Coll Cardiol 2001;38:506 –513. Ferrier KE, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA: Aerobic exercise training does not modify largeartery compliance in isolated systolic hypertension. Hypertension 2001;38:222–226. Pollock ML, Franklin BA, Balady GJ, Chaitman BL, Fleg JL, Fletcher B, Limacher M, Pina IL, Stein RA, Williams M, Bazzarre T: Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: an advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; position paper endorsed by the American College of Sports Medicine. Circulation 2000;101:828 – 833. Miyachi M, Donato AJ, Yamamoto K, Takahashi K, Gates PE, Moreau KL, Tanaka H: Greater age-related reductions in central arterial compliance in resistance-trained men. Hypertension 2003; 41:130 –135. Bertovic DA, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA: Muscular strength training is associated with low arterial compliance and high pulse pressure. Hypertension 1999;33: 1385–1391. MacDougall JD, McKelvie RS, Moroz DE, Sale DG, McCartney N, Buick F: Factors affecting blood pressure during heavy weight lifting and static contractions. J Appl Physiol 1992;73:1590 –1597. Hall JE, Jones DW: What can we do about the “epidemic” of obesity. Am J Hypertens 2002;15:657– 659. Danias PG, Tritos NA, Stuber M, Botnar RM, Kissinger KV, Manning WJ: Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults. Am J Cardiol 2003;91:195–199. Sutton-Tyrrell K, Newman A, Simonsick EM, Havlik R, Pahor M, Lakatta E, Spurgeon H, Vaitkevicius P: Aortic stiffness is associated with visceral adiposity in older adults enrolled in the Study of Health, Aging, and Body Composition. Hypertension 2001;38:429 – 433. Oren S, Grossman E, Frohlich ED: Arterial and venous compliance in obese and nonobese subjects. Am J Cardiol 1996;77:665– 667. Mangoni AA, Giannattasio C, Brunani A, Failla M, Colombo M, Bolla G, Cavagnini F, Grassi GM: Radial artery compliance in young, obese, normotensive subjects. Hypertension 1995;26:984 – 988. Toto-Moukouo JJ, Achimastos A, Asmar RG, Hugues CJ, Safar ME: Pulse wave velocity in patients with obesity and hypertension. Am Heart J 1986;112:136 –140. Singhal A, Farooqi IS, Cole TJ, O’Rahilly S, Fewtrell M, Kattenhorn M, Lucas A, Deanfield J: Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 2002;106:1919 –1924. Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR: Non-insulindependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes: the ARIC study. Circulation 1995;91:1432–1443. Yamashita T, Sasahara T, Pomeroy SE, Collier G, Nestel PJ: Arterial compliance, blood pressure, plasma leptin, and plasma lipids in women are improved with weight reduction equally with a meatbased diet and a plant-based diet. Metabolism 1998;47:1308 –1314. Balkestein EJ, van Aggel-Leijssen DP, van Baak MA, StruijkerBoudier HA, Van Bortel LM: The effect of weight loss with or without exercise training on large artery compliance in healthy obese men. J Hypertens 1999;17:1831–1835.
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26. Mahmud A, Feely J: Divergent effect of acute and chronic alcohol on arterial stiffness. Am J Hypertens 2002;15:240 –243. 27. Waring WS, Goudsmit J, Marwick J, Webb DJ, Maxwell SR: Acute caffeine intake influences central more than peripheral blood pressure in young adults. Am J Hypertens 2003;16:919 –924. 28. Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O’Rourke MF: Caffeine increases aortic stiffness in hypertensive patients. Am J Hypertens 2003;16:63– 66. 29. Elliott P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, Marmot M: INTERSALT revisited: further analyses of 24 h sodium excretion and blood pressure within and across populations. Br Med J 1996;312:1249 –1253. 30. Levenson JA, Simon AC, Maarek BE, Gitelman RJ, Fiessinger JN, Safar ME: Regional compliance of brachial artery and saline infusion in patients with atherosclerosis obliterans. Arteriosclerosis 1985;5:80 – 87. 31. Benjamin N: Effect of salt intake on endothelium-derived factors in a group of essential hypertensive patients. Clin Sci (Lond) 2001; 101:101–102. 32. Avolio AP, Fa-Quan D, Wei-Qiang L, Yao-Fei L, Zhen-Dong H, Lian-Fen X, O’Rourke MF: Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation 1985;71:202–210. 33. Avolio AP, Clyde KM, Beard TC, Cooke HM, Ho KKL, O’Rourke MF: Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis 1986;6:166 –169. 34. Draaijer P, Kool MJ, Maessen JM, van Bortel LM, de Leeuw PW, van Hooff JP, Leunissen KM: Vascular distensibility and compliance in salt-sensitive and salt-resistant borderline hypertension. J Hypertens 1993;11:1199 –1207. 35. Benetos A, Yang-Yan X, Cuche JL, Hannaert P, Safar M: Arterial effects of salt restriction in hypertensive patients: a 9-week, randomized, double-blind crossover study. J Hypertension 1992;10: 355–360. 36. Lambert J, Pijpers R, Ittersum FJ, Comans EFI, Aarsen M, Pieper EJ, Donker AJM, Stehouwer CDA: Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus. Hypertension 1997;30:1162–1168. 37. Gates PE, Tanaka H, Hiatt WR, Seals DR: Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension 2004;44:35– 41. 38. Hamazaki T, Urakaze M, Sawazaki S, Yamazaki K, Taki H, Yano S: Comparison of pulse wave velocity of the aorta between inhabitants of fishing and farming villages in Japan. Atherosclerosis 1988;73:157–160. 39. Wahlqvist ML, Lo CS, Myers KA: Fish intake and arterial wall characteristics in healthy people and diabetic patients. Lancet 1989; 2:944 –946. 40. Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T, Liang YL, Dart AM, Jennings GL, Abbey M, Cameron JD: Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidation. Arterioscler Thromb Vasc Biol 1997; 17:1163–1170. 41. McVeigh GE, Brennan GM, Cohn JN, Finkelstein SM, Hayes RJ, Johnston GD: Fish oil improves arterial compliance in non-insulindependent diabetes mellitus. Arterioscler Thromb 1994;14:1425– 1429. 42. Wilkinson IB, Megson IL, MacCallum H, Sogo N, Cockcroft JR, Webb DJ: Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol 1999;34:690 – 693. 43. Mullan BA, Young IS, Fee H, McCance DR: Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension 2002;40:804 – 809. 44. Mottram P, Shige H, Nestel P: Vitamin E improves arterial compliance in middle-aged men and women. Atherosclerosis 1999;145: 399 – 404.
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45. Asplund K: Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review. J Intern Med 2002;251:372–392. 46. Svetkey LP, Loria CM: Blood pressure effects of vitamin C: what’s the key question? Hypertension 2002;40:789 –791. 47. Eskurza I, Monahan KD, Robinson JA, Seals DR: Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol 2004;286:H1528 –H1534. 48. van Guldener C, Nanayakkara PW, Stehouwer CD: Homocysteine and blood pressure. Curr Hypertens Rep 2003;5:26 –31. 49. Mahmud A, Feely J: Effect of smoking on arterial stiffening and pulse pressure amplification. Hypertension 2003;41:183–187. 50. Brunel P, Girerd X, Laurent S, Pannier B, Safar M: Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol. Eur J Clin Pharmacol 1992;42:143–146. 51. Failla M, Grappiolo A, Carugo S, Calchera I, Giannattasio C, Mancia G: Effects of cigarette smoking on carotid and radial artery distensibility. J Hypertens 1997;15:1659 –1664. 52. Stefanadis C, Vlachopoulos C, Tsiamis E, Diamantopoulos L, Toutouzas K, Giatrakos N, Vaina S, Tsekoura D, Toutouzas P: Unfavorable effects of passive smoking on aortic function in men. Ann Intern Med 1998;128:426 – 434. 53. Stefanadis C, Tsiamis E, Vlachopoulos C, Stratos C, Toutouzas K, Pitsavos C, Marakas S, Boudoulas H, Toutouzas P: Unfavorable effect of smoking on the elastic properties of the human aorta. Circulation 1997;95:31–38. 54. Asmar RG, Girerd XJ, Brahimi M, Safavian A, Safar ME: Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension. J Hypertens 1992;10:181–187. 55. Liang YL, Shiel LM, Teede H, Kotsopoulos D, McNeil J, Cameron JD, McGrath BP: Effects of blood pressure, smoking, and their interaction on carotid artery structure and function. Hypertension 2001;37:6 –11. 56. Levenson J, Simon AC, Cambien FA, Beretti C: Cigarette smoking and hypertension. Factors independently associated with blood hyperviscosity and arterial rigidity. Arteriosclerosis 1987;7:572–577. 57. Kool MJ, Hoeks AP, Struijker Boudier HA, Reneman RS, Van Bortel LM: Short- and long-term effects of smoking on arterial wall properties in habitual smokers. J Am Coll Cardiol 1993;22:1881–1886. 58. Mack WJ, Islam T, Lee Z, Selzer RH, Hodis HN: Environmental tobacco smoke and carotid arterial stiffness. Prev Med 2003;37: 148 –154.
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59. Benowitz NL: Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis 2003;46:91–111. 60. Oncken CA, White WB, Cooney JL, Van Kirk JR, Ahluwalia JS, Giacco S: Impact of smoking cessation on ambulatory blood pressure and heart rate in postmenopausal women. Am J Hypertens 2001;14:942–949. 61. Safar ME, Laurent S, Pannier BM, London GM: Structural and functional modifications of peripheral large arteries in hypertensive patients. J Clin Hypertens 1987;3:360 –367. 62. Nosaka T, Tanaka H, Watanabe I, Sato M, Matsuda M: Influence of regular exercise on age-related changes in arterial elasticity: mechanistic insights from wall compositions in rat aorta. Can J Appl Physiol 2003;28:204 –212. 63. Singh R, Barden A, Mori T, Beilin L: Advanced glycation endproducts: a review. Diabetologia 2001;44:129 –146. 64. Bezie Y, Lamaziere JM, Laurent S, Challande P, Cunha RS, Bonnet J, Lacolley P: Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1998; 18:1027–1034. 65. Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DR, Ulrich P, Brines M, Wuerth JP, Cerami A, Lakatta EG: A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci USA 2001;98:1171–1175. 66. Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG: Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001;104:1464 –1470. 67. Barenbrock M, Spieker C, Witta J, Evers S, Hoeks APG, Rahn KH, Zidek W: Reduced distensibility of the common carotid artery in patients treated with ergotamine. Hypertension 1996;28:115–119. 68. Boutouyrie P, Locolley P, Girerd X, Beck L, Safar M, Laurent S: Sympathetic activation decreases medium-sized arterial compliance in humans. Am J Physiol 1994;267:H1368 –H1376. 69. Kinlay S, Creager MA, Fukumoto M, Hikita H, Fang JC, Selwyn AP, Ganz P: Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo. Hypertension 2001;38:1049 –1053. 70. Izzo JL Jr: Arterial stiffness and the systolic hypertension syndrome. Curr Opin Cardiol 2004;19:341–352. 71. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME: Aortic pulse wave velocity predicts cardiovascular mortality in subjects ⬎70 years of age. Arterioscler Thromb Vasc Biol 2001;21:2046 –2050.
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Influence of Lifestyle Modification on Arterial Stiffness and Wave Reflections Hirofumi Tanaka and Michel E. Safar Arterial stiffness and wave reflections exert a number of adverse effects on cardiovascular function and disease risk and are associated with a greater rate of mortality in patients with end-stage renal failure and essential hypertension. Accordingly, the prevention and treatment of arterial stiffness are of paramount importance. Because arterial stiffening is being recognized as a critical precursor of cardiovascular disease (CVD), it is essential to understand the role of lifestyle modifications on preventing and reversing arterial stiffening. Available evidence indicates that lifestyle modifications, in particular aerobic exercise and sodium restriction, appear to be clinically
efficacious therapeutic interventions for preventing and treating arterial stiffening. Thus, sufficient evidence is available to recommend lifestyle modifications as part of a first-line therapeutic approach for arterial stiffening. However, more information is needed for a full understanding and optimal use of lifestyle modifications in the management of arterial stiffening. Am J Hypertens 2005;18: 137–144 © 2005 American Journal of Hypertension, Ltd.
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modifications, and smoking cessation. Much of the confusion in the field of arterial stiffness arises from the different terminologies and methodologies used to express the elastic properties of an artery.3 In this review, we specified the methodology used in each study so that readers can assess each study with their own judgments. Interested readers may refer to a recent consensus report that reviewed various methodologies to assess arterial stiffness.3
Key Words: Nonpharmacological, arterial compliance, exercise, sodium restriction.
arge elastic arteries expand and recoil with cardiac pulsation and relaxation. During systole, a significant portion of the ejected stroke volume is stored by arterial distention, which acts to buffer the rise in systolic pressure and to convert pulsatile cardiac ejection into continuous blood flow in capillary beds. Reductions in arterial compliance and increases in arterial stiffness are believed to contribute to the pathophysiology of cardiovascular disease (CVD) and have recently been identified as powerful and independent risk factors for CVD.1,2 Increased arterial stiffness can contribute to the development and progression of hypertension, left ventricular hypertrophy, myocardial infarction, and congestive heart failure.1 For most risk factors for CVD, the first-line approach for prevention and treatment for development of CVD is lifestyle modification (Fig. 1). Given the role of arterial stiffness as a critical precursor of CVD,2 it is important to recognize the effects of lifestyle modifications for the prevention and treatment of arterial stiffening. An emerging body of evidence supports the concept that lifestyle modifications can prevent and reverse arterial stiffening. This article reviews the evidence regarding the influence of lifestyle modifications on arterial stiffening and wave reflections. The focus will be placed on increased physical activity, weight loss, a reduced salt intake, other dietary
A cross-sectional study from the Baltimore Longitudinal Study of Aging found that older men who performed endurance exercise on a regular basis demonstrated lower levels of aortic pulse wave velocity (PWV) and carotid augmentation index (AI; an indicator of the magnitude of arterial wave reflection and arterial stiffness) than did their sedentary peers.4 We also reported that significant agerelated increases in central arterial stiffness (aortic PWV and carotid augmentation index) were absent in physically active postmenopausal women and that aerobic fitness was strongly associated with arterial stiffness.5 Physically active individuals often demonstrate resting bradycardia, which could act on wave reflections and pulse pressure
Received June 4, 2004. First decision July 12, 2004. Accepted July 13, 2004. From the Department of Kinesiology and Health Education (HT), University of Texas, Austin, Texas; and Centre de Diagnostic (MES), Hôpital Hôtel Dieu, Paris, France.
Research supported by National Institutes of Health grants AG00847 and AG020966. Address correspondence and reprint requests to Dr. Hirofumi Tanaka, Department of Kinesiology and Health Education, University of Texas, Austin, TX 78712; e-mail: [email protected]
© 2005 by the American Journal of Hypertension, Ltd. Published by Elsevier Inc.
Regular Exercise Aerobic (Endurance) Exercise
0895-7061/05/$30.00 doi:10.1016/j.amjhyper.2004.07.008
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FIG. 1 Processes of arterial stiffening and destiffening. AGEs ⫽ advanced glycation end-products.
amplifications.6 However, there are no consistent associations between resting heart rate and arterial stiffness in these studies involving endurance-trained adults.5,7,8 In contrast to the effects on central elastic artery, peripheral arterial stiffness (leg PWV and arm PWV) was not different between sedentary and physically active adults.5 These cross-sectional findings provide support for the role of regular aerobic exercise in the primary prevention of central arterial stiffening and wave reflections. However, athletic and sedentary adults may differ in terms of many constitutional factors. To demonstrate the direct effect of regular exercise on arterial stiffness, interventional studies are required. Unknown to most, the first intervention study to determine the influence of exercise training on arterial stiffness was conducted in Japan. After 9 months of physical training incorporating a variety of exercises including jogging, soccer, handball, and judo, Ikegami et al9 found a small but significant reduction in aortic PWV in 80 healthy young Japanese men. We recently completed an exercise intervention study involving previously sedentary but healthy middle-aged and older men, and reported that a relatively brief period (3 months) of aerobic exercise can increase carotid arterial compliance as measured with a simultaneous application of high-resolution ultrasound and applanation tonometry (Fig. 2).8 This improvement was not associated with changes in body weight, adiposity, blood pressure (BP), plasma cholesterol, or resting heart rate, indicating a direct effect of exercise on arterial compliance. Importantly, this was accomplished with an intensity (moderate) and type (walking) of physical activity that
can be performed by most, if not all, healthy older adults.8 In contrast to central elastic arteries, the compliance of the peripheral muscular artery did not change with exercise training,8 indicating that the effect of resistance training involves only central elastic arteries, which have a cushioning function that dampens fluctuations in pressure and flow. Because the effects of exercise training were observed only on the central elastic artery (carotid artery) but not on the peripheral muscular artery (ie, femoral artery), it is possible to hypothesize that some mechanical/physical (local) factors may have interacted with structural or functional mechanisms to improve arterial compliance. We recently prescribed an identical aerobic exercise program
Arterial Compliance (mm2/mmHg) 0.20
* 0.15 1.5±0.2 1.2±0.1
0.10
0.05 Before Training
After Training
FIG. 2 Carotid arterial compliance before and after 3 months of aerobic exercise intervention.8
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to middle-aged and older women and found that women appear to benefit from regular aerobic exercise to a greater extent than do men (40% v 25%).7 Taken together, these results suggest that habitual aerobic exercise may be an effective lifestyle intervention for augmenting central arterial compliance in healthy adults. Available evidence indicates that short-term aerobic exercise intervention may not be as effective in reducing arterial stiffness in a patient population as in healthy adults. For example, we recently reported that 3 months of exercise intervention produced only small reductions in aortic PWV and augmentation index in postmenopausal women with elevated systolic BP.10 In another study, short-term aerobic exercise training was unable to increase systemic arterial compliance in patients with isolated systolic hypertension.11 It is possible that the plasticity of the arterial function to adapt to exercise training may diminish as arteries are exposed to chronically elevated BP. Because hypertensive patients are arguably the greatest beneficiaries of destiffening therapy, larger scale studies are warranted to investigate the potential efficacy of long-term aerobic exercise intervention on arterial stiffness in this population. Resistance (Weight) Training In recent years, statements on physical activity by various health organizations have recommended weight training as part of a preventive and rehabilitative program of physical activity.12 These recommendations are based primarily on the documented impact of weight training on the attenuation of osteoporosis and sarcopenia as well as on the emerging beneficial effects on metabolic risk factors. Given this, it is reasonable to hypothesize that weight training would be associated with reduced arterial stiffness. However, the currently available evidence does not support this.13,14 In our recent study,13 sedentary and resistance-trained men were carefully matched for age, height, BP, heart rate, and metabolic risk factors to isolate the influence of resistance training as much as possible. Additionally, in an attempt to isolate the effect of longterm resistance training per se, we excluded those who had been concurrently performing endurance training and those taking anabolic steroids or other performance enhancing drugs. However, middle-aged men who performed resistance training on a regular basis demonstrated greater levels of arterial stiffness compared with their sedentary peers.13 It is possible that the marked elevations in arterial BP, as high as 320/250 mm Hg,15 during weight lifting, may result in long-term increases in the smooth muscle content of the arterial wall and the load-bearing properties of collagen and elastin, thereby increasing arterial stiffness. Indeed, carotid arterial compliance was modestly but significantly associated with carotid wall thickness. Given the well known limitation of cross-sectional study design and the conflicting results between aerobic and strength training, these cross-sectional study
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findings should be confirmed prospectively with the interventional approach.
Weight Reduction Obesity is a major public health problem with markedly increased morbidity and mortality risks from nearly all of the common CVD. In particular, obesity is closely linked with the development of hypertension.16 Several studies have investigated the relation between obesity and large arterial functions with contradictory results. In some studies, obese subjects have been found to have higher degrees of arterial stiffness,17,18 and in other studies lower degrees.19,20 These discordant results may be due to the method used to describe mechanical wall properties of arteries. For example, obese subjects are expected to have larger stroke volume and cardiac output simply because of the larger body size, and this could influence some measures of arterial distensibility (such as systemic arterial compliance and stroke volume/pulse pressure ratio) that rely on stroke volume. These methodologic artifacts could explain, at least in part, the paradoxically smaller degree of arterial stiffness reported in obese subjects. Similarly, the estimation of arterial length required for the PWV measurements may not be accurate in obese individuals. Moreover, arterial compliance measurements using ultrasonography may be limited by decreased acoustic penetration and its dependence on lumen diameter, which tends to be greater in obese individuals. Studies using the measures of arterial stiffness that are relatively free of these methodologic issues (eg, MRI) have consistently demonstrated that obese as well as overweight individuals have increased levels of arterial stiffness17,21 and that measures of adiposity are closely and positively associated with arterial stiffness.18,21 Interestingly, a recent study reported that brachial artery distensibility was associated with fasting serum leptin concentration.22 Because obesity is closely associated with the development of insulin resistance and the metabolic syndrome, it is not surprising that arterial stiffness is found to be increased in these disease states.23 Few interventional studies have investigated the effects of weight loss on arterial stiffness, and most of them are short-term studies lasting between 4 and 16 weeks.21,24,25 In one of the first studies to address this, a group of investigators from Paris reported that 4 weeks of caloric restriction, which aimed to achieve a 10% to 15% reduction in body weight, induced significant reductions in BP and aortic PWV in nine obese hypertensive subjects.21 Moreover, in normotensive obese men, 3 months on an energy-restricted diet induced a significant reduction in body weight, which was associated with reductions in large artery stiffness.25 The improvement in the elastic properties of arteries observed in this study, however, appears to be dependent on the accompanied reductions in arterial BP, because no change in arterial stiffness was observed when it was measured under isobaric condi-
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tions.25 In obese women, a 16-week weight loss program achieved ⬃10% reduction in body weight and induced ⬃30% increase in systemic arterial compliance.24 The increase in arterial compliance was significantly but modestly associated with the reduction in BP, suggesting that the effect of weight reduction on arterial distensibility may be mediated indirectly by the concomitant decreases in BP. However, there was a subgroup of women who achieved significant reductions in arterial stiffness without any changes in arterial BP.24 Thus, the available evidence indicates that weight reduction may decrease arterial stiffness in obese subjects. However, currently it is not clear whether the reduction in arterial stiffness is due to weight reduction per se or whether it is an epiphenomenon of BP reductions accompanying weight loss. The direct effects of weight reduction on arterial stiffness should be investigated in the future in obese subjects in general and in obese hypertensive subjects in particular.
Dietary Modifications There is now overwhelming evidence that dietary factors influence the risk of cardiovascular disease, and emerging data indicate that arterial stiffness is markedly influenced by dietary factors. Red wine containing alcohol induced small but significant reductions in BP, PWV, and AI obtained at the radial artery.26 These effects were not observed when dealcoholized wine was consumed. Although part of the effect of alcohol appears to be BP dependent, the reduction in arterial stiffness remained significant even after adjusting for BP changes.26 Recent studies indicate that caffeine intake, in the form of a tablet27 or in coffee,28 produces a short-term increase in AI obtained at the radial artery in normotensive27 and hypertensive28 subjects. No such changes were seen with placebo27 or decaffeinated coffee intake.28 Taken together, these studies suggest that arterial stiffness can be changed acutely with commonly consumed dietary factors. Sodium Restriction Salt intake is being recognized as an important factor determining the BP differences between and within populations and is a major cause of the rise in arterial BP with advancing age.29 Increased salt intake is thought to raise BP by increasing plasma volume, blood volume, and subsequently cardiac output. Although this could be true in short-term experiments involving saline infusion,30 the evidence that the chronic increase in cardiac output is responsible for salt-induced increase in BP is not convincing,31 because increased blood volume is associated with increased venous compliance with little change in central venous pressure and cardiac output. Alternatively, there is increasing evidence supporting the link between sodium intake and arterial stiffness. The INTERSALT Study indicates that excess intake of sodium, as reflected in 24-h urinary sodium excretion, is associated with an increase in systolic BP but not in diastolic BP.29 Additionally, aortic
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FIG. 3 Carotid arterial compliance at baseline, in each of 4 weeks of the low sodium condition, and during the 4 weeks of the normal sodium condition.37
PWV was measured in groups of individuals living in a rural or an urban community in China.32 Aortic PWV was significantly lower in the rural community with low salt intake, and the group difference persisted even when subgroups of subjects with the same BP and age were compared.32 Cross-sectional findings in normotensive adults varying in age indicate that subjects who follow a diet low in sodium demonstrate lower levels of PWV than age- and BP-matched controls with higher salt intake.33 Moreover, borderline hypertensive subjects who are sodium sensitive with regard to BP have decreased arterial distensibility compared with sodium-resistant subjects.34 Plasma volume, cardiac output, and BP were not different between sodium-sensitive and sodium-resistant subjects and could not have been responsible for observed differences in arterial stiffness.34 Taken together, these cross-sectional findings support the hypothesis that sodium intake influences arterial stiffness long term, independent of BP. There have been only a few intervention studies that determined the effects of salt restriction on arterial stiffness.10,35,36 We reported that in postmenopausal women with elevated BP, 3 months of moderate dietary sodium restriction reduced both casual and 24-h BP.10 The changes in resting and 24-h systolic BP and pulse pressure were consistently correlated with the corresponding changes in both aortic PWV and carotid AI. Importantly, the reductions in carotid AI were not associated with changes in body weight, mean BP, plasma volume, and heart rate,10 indicating a direct effect of sodium restriction on arterial stiffness. An interesting observation in this study is that sodium restriction was more efficacious in reducing BP and arterial stiffness than a moderate aerobic exercise program in postmenopausal women.10 We recently followed-up this previous study using carotid arterial compliance measured with a simultaneous application of ultrasonography and applanation tonometry.37 A novel finding of this study is that arterial compliance increased very rapidly at the end of week 1 of sodium restriction, attaining peak levels by week 2 (Fig. 3).
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Other Dietary Modifications To date, a number of short-term dietary modifications have been shown to change the elastic properties of large arteries, although most studies have involved a relatively small number of subjects. A comparison of aortic PWV between inhabitants of fishing and farming villages in Japan revealed that the population with higher fish consumption demonstrated lower arterial stiffness.38 In an Australian cross-sectional study involving both healthy and diabetic subjects, fish eaters demonstrated a greater arterial compliance compared with non–fish eaters who were matched for age, BMI, and BP.39 These cross-sectional study findings were confirmed by interventional studies. In placebo-controlled studies, several weeks of fish oil supplementation with n-3 fatty acid significantly improved arterial wall characteristics in obese subjects40 as well as in diabetic subjects.41 Collectively, these findings are consistent with the hypothesis that fish oils, more specifically n-3 fatty acids, may reduce arterial stiffness. The antioxidant vitamins, in particular ascorbic acid and ␣-tocopherol, have been reported to reduce arterial stiffness. In a placebo-controlled, double-blind, randomized study, AI measured at the radial artery was reduced 6 h after oral intake of vitamin C in healthy subjects.42 The results of this short-term study are in agreement with a recent intervention study involving diabetic patients.43 After 4 weeks of oral intake of ascorbic acid, aortic AI estimated from the radial artery waveform decreased significantly.43 It should be noted, however, that reductions in peripheral resistance, which could be induced by vitamin C intake, may be responsible for the reduction in AI. Similarly, 8 weeks of vitamin E intake induced 44% increase in systemic arterial compliance in middle-aged men and women.44 These results suggest that the antioxidant vitamin may be beneficial in reversing arterial stiffening, presumably through its effect as free radical scavenger. Although the available data regarding the effects of vitamins on arterial stiffness are encouraging, there appears to be little evidence that supplements of vitamin C or E are sufficiently effective in preventing and controlling high BP or cardiovascular disease (that is, sequelae of arterial stiffening).45,46 Thus, the clinical significance of the short-term effects of vitamins on arterial stiffness remains to be determined. In fact, a recent wellcontrolled study involving both short-term and long-term administration of ascorbic acid failed to affect carotid arterial compliance in healthy young and older men.47 Similarly, homocysteine lowering therapy with folic acidbased treatments have been shown to be ineffective in improving carotid artery compliance.48 Thus, available information is not encouraging in terms of recommending antioxidant vitamins for the prevention and treatment of arterial stiffening and subsequent CVD. Smoking Cessation Smoking is a major and independent risk factor for development and progression of cardiovascular disease. Despite
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the strong evidence linking cigarette smoking and cardiovascular disease, the mechanisms by which smoking causes cardiovascular disease remain poorly understood. In addition to smoking-induced endothelial dysfunction, emerging evidence indicates that smoking may exert its effects, at least in part, through decreasing arterial compliance. Short-term cigarette smoking was found to increase arterial stiffness in nonsmokers49,50 and smokers,49,51,52 and the magnitude of increases in arterial stiffness after smoking was similar between the two groups.49 The greatest effects of short-term smoking on arterial stiffness seem to occur in the first 5 minutes after smoking,49,53 and ambulatory BP measurements indicate that smoking increases pulse pressure during day but not at night (that is, when subjects do not smoke).54 A recent study has demonstrated that “passive” or environmental smoking is also associated with acute deterioration in the elastic properties of the aorta.52 Consistent with the short-term effects of smoking, the majority of studies to date have reported that long-term smoking is associated with arterial stiffening,55,56 although there are some conflicting reports.57 The effects of longterm smoking on arterial stiffness have been observed both in normotensive and hypertensive individuals55,56 and appear to be independent of BP levels.56 Long-term exposure to environmental tobacco smoke (ie, passive smoking) also is associated with carotid arterial stiffening in a dosedependent manner.58 These results indicate that some chemicals in the gas may be a cause of smoking-induced arterial stiffening. In this context, exposure to oxidizing gases may be a primary suspect, as blood levels of nicotine and carbon monoxide are quite low in passive smokers59 who also demonstrate arterial stiffening. To the best of our knowledge, there has been no study to determine directly whether smoking cessation would reduce stiffnness in large elastic arteries. However, because several weeks of smoking cessation reduces systolic BP in hypertensive patients,60 it is reasonable to hypothesize that arterial stiffness would be reduced with smoking cessation. Nonetheless, the information regarding the influence of smoking cessation on arterial stiffness should be derived in future studies.
Physiological Mechanisms Underlying Arterial Destiffening The three primary elements of the arterial wall that determine its stiffness are as follows: 1) the amount/proportion of elastin and collagen (quantitative structural elements); 2) fracture/fragmentation of elastic lamellae and the crosslinking of collagen and advanced glycation end-products (qualitative structural elements); and 3) the vasoconstrictor tone exerted by its smooth muscle cells (functional elements) (Fig. 1). Although different lifestyle modifications would likely act on different physiologic mechanisms to change arterial stiffness, any favorable influences of lifestyle modifications should involve an attenuation or
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reversal of one or more of the mechanisms contributing to arterial stiffening. It is thought that structural changes, in particular elastin and collagen content, play a major role in determining central arterial stiffness. However, the elastin– collagen composition of the arterial wall represents a more longterm component of the stiffness of the artery and changes only over a period of years.61 As such, it is unlikely that this may be a physiologic mechanism underlying reductions in arterial stiffness induced by short-term lifestyle modifications described above. In fact, in an animal experiment, we recently demonstrated that the influence of regular aerobic exercise on arterial stiffness does not appear to be mediated by the quantitative changes in arterial wall elastin and collagen.62 In addition to the “quantitative” changes, the constituents of arterial wall undergo “qualitative” changes with age, hypertension, and diabetes (for example, fracture and fragmentation of elastic lamellae as well as changes and remodeling of extracellular matrix, including fibronectin and integrin).63,64 In particular, there is an accumulation of additional interstitial collagen in the arterial wall,63 which can react nonenzymatically with glucose, link them together, and produce advanced glycation end-products.63 These end-products accumulate slowly on long-lived proteins to stiffen arteries.63 It is plausible to hypothesize that some lifestyle interventions, such as exercise, may act to break these links to reduce arterial stiffness. In this context, the agents that break these protein cross-links reduce arterial stiffness in aged monkeys65 as well as in aged adults.66 Because this favorable effect can be induced in several weeks,65,66 it is reasonable to hypothesize that some lifestyle modifications may act on arterial stiffness via this mechanism. In marked contrast to the prevailing thought that arterial stiffness is a relatively static measure, arterial stiffness has a large “reserve” and can be altered— even acutely— over a much shorter period.67,68 The ability to modify arterial stiffness over the short term is thought to be due to modulation of the contractile states of the vascular smooth muscle cells in the arterial wall.67,68 As such, it is possible that the reduction in vasoconstrictor tone exerted by smooth muscle cells may be a potential mechanism underlying improvements in arterial stiffness with lifestyle modifications. Another related and plausible mechanism contributing to the reduction in arterial stiffness is reduced vascular endothelium mediated vasodilator tone. The augmented nitric oxide bioavailability should tonically suppress vascular smooth muscle cell tone, thereby reducing arterial stiffness. In this context, nitric oxide was recently shown to regulate brachial artery elasticity in humans.69
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crease in systolic BP, which acts to reverse cardiac hypertrophy, and an increase in diastolic BP, which improves coronary circulation, treatments that reduce pulse pressure and arterial stiffness may further reduce cardiovascular risks. It is a matter of debate as to whether a direct measurement of arterial stiffness would provide a greater increment in cardiovascular risk stratification over an indirect index, including systolic and pulse pressure.70 However, systolic and pulse pressure lose their predictive power for cardiovascular events after adjustment for arterial stiffness, and arterial stiffness exerts the stronger independent predictive power.71 As such, arterial stiffness should be considered as a marker of cardiovascular risk independent of brachial BP levels. Current guidelines recommend that to prevent and treat most cardiovascular risk factors, lifestyle modifications be used for an initial period of 3 to 6 months, followed by pharmacological intervention if necessary to achieve normalization. Available evidence indicates that lifestyle modifications—in particular, aerobic exercise and sodium restriction—appear to be clinically efficacious therapeutic interventions for preventing and treating arterial stiffening. Thus, sufficient evidence is available to recommend lifestyle modifications as part of a first-line therapeutic approach for arterial stiffening. However, more information is needed for a more complete understanding and optimal use of lifestyle modifications in the management of arterial stiffening.
References 1.
2.
3.
4.
5.
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Perspectives Arterial stiffening and increased pulse pressure are being recognized as predictors of CVD, in particular myocardial infarction. Because reduced pulse pressure involves a de-
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Safar ME, London GM: Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. The Clinical Committee of Arterial Structure and Function. J Hypertens 2000;18:1527–1535. Hodes RJ, Lakatta EG, McNeil CT: Another modifiable risk factor for cardiovascular disease? Some evidence points to arterial stiffness. J Am Geriatr Soc 1995;43:581–582. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE: Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens 2002;15:426 – 444. Vaitkevicious PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, Yin FCP, Lakatta EG: Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 1993;88: 1456 –1462. Tanaka H, DeSouza CA, Seals DR: Absence of age-related increase in central arterial stiffness in physically active women. Arterioscler Thromb Vasc Biol 1998;18:127–132. Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ: The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol (Lond) 2000;525:263– 270. Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H: Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res 2003;57:861– 868. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR: Aging, habitual exercise, and dynamic arterial compliance. Circulation 2000;102:1270 –1275.
AJH–January 2005–VOL. 18, NO. 1
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10.
11.
12.
13.
14.
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16. 17.
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19. 20.
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Ikegami H, Satake M, Kurokawa T, Tan N, Sugiura T, Yamazaki Y: Effects of physical training on body composition, respiro-circulatory functions, blood constituents, and physical abilities. Part 1: men aged 30 years. J Phys Fitness Japan 1983;32:302–309. Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, Hiatt WR, Davy KP, DeSouza CA: Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness. J Am Coll Cardiol 2001;38:506 –513. Ferrier KE, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA: Aerobic exercise training does not modify largeartery compliance in isolated systolic hypertension. Hypertension 2001;38:222–226. Pollock ML, Franklin BA, Balady GJ, Chaitman BL, Fleg JL, Fletcher B, Limacher M, Pina IL, Stein RA, Williams M, Bazzarre T: Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: an advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; position paper endorsed by the American College of Sports Medicine. Circulation 2000;101:828 – 833. Miyachi M, Donato AJ, Yamamoto K, Takahashi K, Gates PE, Moreau KL, Tanaka H: Greater age-related reductions in central arterial compliance in resistance-trained men. Hypertension 2003; 41:130 –135. Bertovic DA, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA: Muscular strength training is associated with low arterial compliance and high pulse pressure. Hypertension 1999;33: 1385–1391. MacDougall JD, McKelvie RS, Moroz DE, Sale DG, McCartney N, Buick F: Factors affecting blood pressure during heavy weight lifting and static contractions. J Appl Physiol 1992;73:1590 –1597. Hall JE, Jones DW: What can we do about the “epidemic” of obesity. Am J Hypertens 2002;15:657– 659. Danias PG, Tritos NA, Stuber M, Botnar RM, Kissinger KV, Manning WJ: Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults. Am J Cardiol 2003;91:195–199. Sutton-Tyrrell K, Newman A, Simonsick EM, Havlik R, Pahor M, Lakatta E, Spurgeon H, Vaitkevicius P: Aortic stiffness is associated with visceral adiposity in older adults enrolled in the Study of Health, Aging, and Body Composition. Hypertension 2001;38:429 – 433. Oren S, Grossman E, Frohlich ED: Arterial and venous compliance in obese and nonobese subjects. Am J Cardiol 1996;77:665– 667. Mangoni AA, Giannattasio C, Brunani A, Failla M, Colombo M, Bolla G, Cavagnini F, Grassi GM: Radial artery compliance in young, obese, normotensive subjects. Hypertension 1995;26:984 – 988. Toto-Moukouo JJ, Achimastos A, Asmar RG, Hugues CJ, Safar ME: Pulse wave velocity in patients with obesity and hypertension. Am Heart J 1986;112:136 –140. Singhal A, Farooqi IS, Cole TJ, O’Rahilly S, Fewtrell M, Kattenhorn M, Lucas A, Deanfield J: Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 2002;106:1919 –1924. Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR: Non-insulindependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes: the ARIC study. Circulation 1995;91:1432–1443. Yamashita T, Sasahara T, Pomeroy SE, Collier G, Nestel PJ: Arterial compliance, blood pressure, plasma leptin, and plasma lipids in women are improved with weight reduction equally with a meatbased diet and a plant-based diet. Metabolism 1998;47:1308 –1314. Balkestein EJ, van Aggel-Leijssen DP, van Baak MA, StruijkerBoudier HA, Van Bortel LM: The effect of weight loss with or without exercise training on large artery compliance in healthy obese men. J Hypertens 1999;17:1831–1835.
LIFESTYLE MODIFICATIONS AND ARTERIAL STIFFNESS
143
26. Mahmud A, Feely J: Divergent effect of acute and chronic alcohol on arterial stiffness. Am J Hypertens 2002;15:240 –243. 27. Waring WS, Goudsmit J, Marwick J, Webb DJ, Maxwell SR: Acute caffeine intake influences central more than peripheral blood pressure in young adults. Am J Hypertens 2003;16:919 –924. 28. Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O’Rourke MF: Caffeine increases aortic stiffness in hypertensive patients. Am J Hypertens 2003;16:63– 66. 29. Elliott P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, Marmot M: INTERSALT revisited: further analyses of 24 h sodium excretion and blood pressure within and across populations. Br Med J 1996;312:1249 –1253. 30. Levenson JA, Simon AC, Maarek BE, Gitelman RJ, Fiessinger JN, Safar ME: Regional compliance of brachial artery and saline infusion in patients with atherosclerosis obliterans. Arteriosclerosis 1985;5:80 – 87. 31. Benjamin N: Effect of salt intake on endothelium-derived factors in a group of essential hypertensive patients. Clin Sci (Lond) 2001; 101:101–102. 32. Avolio AP, Fa-Quan D, Wei-Qiang L, Yao-Fei L, Zhen-Dong H, Lian-Fen X, O’Rourke MF: Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation 1985;71:202–210. 33. Avolio AP, Clyde KM, Beard TC, Cooke HM, Ho KKL, O’Rourke MF: Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis 1986;6:166 –169. 34. Draaijer P, Kool MJ, Maessen JM, van Bortel LM, de Leeuw PW, van Hooff JP, Leunissen KM: Vascular distensibility and compliance in salt-sensitive and salt-resistant borderline hypertension. J Hypertens 1993;11:1199 –1207. 35. Benetos A, Yang-Yan X, Cuche JL, Hannaert P, Safar M: Arterial effects of salt restriction in hypertensive patients: a 9-week, randomized, double-blind crossover study. J Hypertension 1992;10: 355–360. 36. Lambert J, Pijpers R, Ittersum FJ, Comans EFI, Aarsen M, Pieper EJ, Donker AJM, Stehouwer CDA: Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus. Hypertension 1997;30:1162–1168. 37. Gates PE, Tanaka H, Hiatt WR, Seals DR: Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension 2004;44:35– 41. 38. Hamazaki T, Urakaze M, Sawazaki S, Yamazaki K, Taki H, Yano S: Comparison of pulse wave velocity of the aorta between inhabitants of fishing and farming villages in Japan. Atherosclerosis 1988;73:157–160. 39. Wahlqvist ML, Lo CS, Myers KA: Fish intake and arterial wall characteristics in healthy people and diabetic patients. Lancet 1989; 2:944 –946. 40. Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T, Liang YL, Dart AM, Jennings GL, Abbey M, Cameron JD: Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidation. Arterioscler Thromb Vasc Biol 1997; 17:1163–1170. 41. McVeigh GE, Brennan GM, Cohn JN, Finkelstein SM, Hayes RJ, Johnston GD: Fish oil improves arterial compliance in non-insulindependent diabetes mellitus. Arterioscler Thromb 1994;14:1425– 1429. 42. Wilkinson IB, Megson IL, MacCallum H, Sogo N, Cockcroft JR, Webb DJ: Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol 1999;34:690 – 693. 43. Mullan BA, Young IS, Fee H, McCance DR: Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension 2002;40:804 – 809. 44. Mottram P, Shige H, Nestel P: Vitamin E improves arterial compliance in middle-aged men and women. Atherosclerosis 1999;145: 399 – 404.
144
LIFESTYLE MODIFICATIONS AND ARTERIAL STIFFNESS
45. Asplund K: Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review. J Intern Med 2002;251:372–392. 46. Svetkey LP, Loria CM: Blood pressure effects of vitamin C: what’s the key question? Hypertension 2002;40:789 –791. 47. Eskurza I, Monahan KD, Robinson JA, Seals DR: Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol 2004;286:H1528 –H1534. 48. van Guldener C, Nanayakkara PW, Stehouwer CD: Homocysteine and blood pressure. Curr Hypertens Rep 2003;5:26 –31. 49. Mahmud A, Feely J: Effect of smoking on arterial stiffening and pulse pressure amplification. Hypertension 2003;41:183–187. 50. Brunel P, Girerd X, Laurent S, Pannier B, Safar M: Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol. Eur J Clin Pharmacol 1992;42:143–146. 51. Failla M, Grappiolo A, Carugo S, Calchera I, Giannattasio C, Mancia G: Effects of cigarette smoking on carotid and radial artery distensibility. J Hypertens 1997;15:1659 –1664. 52. Stefanadis C, Vlachopoulos C, Tsiamis E, Diamantopoulos L, Toutouzas K, Giatrakos N, Vaina S, Tsekoura D, Toutouzas P: Unfavorable effects of passive smoking on aortic function in men. Ann Intern Med 1998;128:426 – 434. 53. Stefanadis C, Tsiamis E, Vlachopoulos C, Stratos C, Toutouzas K, Pitsavos C, Marakas S, Boudoulas H, Toutouzas P: Unfavorable effect of smoking on the elastic properties of the human aorta. Circulation 1997;95:31–38. 54. Asmar RG, Girerd XJ, Brahimi M, Safavian A, Safar ME: Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension. J Hypertens 1992;10:181–187. 55. Liang YL, Shiel LM, Teede H, Kotsopoulos D, McNeil J, Cameron JD, McGrath BP: Effects of blood pressure, smoking, and their interaction on carotid artery structure and function. Hypertension 2001;37:6 –11. 56. Levenson J, Simon AC, Cambien FA, Beretti C: Cigarette smoking and hypertension. Factors independently associated with blood hyperviscosity and arterial rigidity. Arteriosclerosis 1987;7:572–577. 57. Kool MJ, Hoeks AP, Struijker Boudier HA, Reneman RS, Van Bortel LM: Short- and long-term effects of smoking on arterial wall properties in habitual smokers. J Am Coll Cardiol 1993;22:1881–1886. 58. Mack WJ, Islam T, Lee Z, Selzer RH, Hodis HN: Environmental tobacco smoke and carotid arterial stiffness. Prev Med 2003;37: 148 –154.
AJH–January 2005–VOL. 18, NO. 1
59. Benowitz NL: Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis 2003;46:91–111. 60. Oncken CA, White WB, Cooney JL, Van Kirk JR, Ahluwalia JS, Giacco S: Impact of smoking cessation on ambulatory blood pressure and heart rate in postmenopausal women. Am J Hypertens 2001;14:942–949. 61. Safar ME, Laurent S, Pannier BM, London GM: Structural and functional modifications of peripheral large arteries in hypertensive patients. J Clin Hypertens 1987;3:360 –367. 62. Nosaka T, Tanaka H, Watanabe I, Sato M, Matsuda M: Influence of regular exercise on age-related changes in arterial elasticity: mechanistic insights from wall compositions in rat aorta. Can J Appl Physiol 2003;28:204 –212. 63. Singh R, Barden A, Mori T, Beilin L: Advanced glycation endproducts: a review. Diabetologia 2001;44:129 –146. 64. Bezie Y, Lamaziere JM, Laurent S, Challande P, Cunha RS, Bonnet J, Lacolley P: Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1998; 18:1027–1034. 65. Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DR, Ulrich P, Brines M, Wuerth JP, Cerami A, Lakatta EG: A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci USA 2001;98:1171–1175. 66. Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG: Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001;104:1464 –1470. 67. Barenbrock M, Spieker C, Witta J, Evers S, Hoeks APG, Rahn KH, Zidek W: Reduced distensibility of the common carotid artery in patients treated with ergotamine. Hypertension 1996;28:115–119. 68. Boutouyrie P, Locolley P, Girerd X, Beck L, Safar M, Laurent S: Sympathetic activation decreases medium-sized arterial compliance in humans. Am J Physiol 1994;267:H1368 –H1376. 69. Kinlay S, Creager MA, Fukumoto M, Hikita H, Fang JC, Selwyn AP, Ganz P: Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo. Hypertension 2001;38:1049 –1053. 70. Izzo JL Jr: Arterial stiffness and the systolic hypertension syndrome. Curr Opin Cardiol 2004;19:341–352. 71. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME: Aortic pulse wave velocity predicts cardiovascular mortality in subjects ⬎70 years of age. Arterioscler Thromb Vasc Biol 2001;21:2046 –2050.