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Peripheral Artery Disease in Hypertension
CHAPTER
3 3 Peripheral Artery Disease in Hypertension Michael H. Criqui and Matthew A. Allison
EPIDEMIOLOGY OF PERIPHERAL ARTERY DISEASE, 296 Prevalence, 296 Risk Factors, 296 Outcomes, 297 CAUSES OF PERIPHERAL ARTERY DISEASE, 297 HYPERTENSION AS A CONTRIBUTING FACTOR TO PERIPHERAL ARTERY DISEASE, 297 Intermittent Claudication Prevalence, 297 Ankle-Brachial Index Prevalence, 297
Peripheral Artery Disease Prevalence by Multiple Noninvasive Tests, 298 Peripheral Artery Disease Prevalence by Angiography, 298 Incidence Studies, 299 Peripheral Artery Disease Progression, 299 Randomized Control Trials, 299 Outcomes Studies of Those with Peripheral Artery Disease and Hypertension, 300 Conclusions, 300
Epidemiology of Peripheral Artery Disease Peripheral artery disease (PAD) is a chronic disease of the large conduit arteries in the lower extremities primarily caused by a significant atherosclerotic burden resulting in luminal obstruction. This condition is often associated with considerable functional limitations.1 The clinical diagnosis of PAD can be confirmed using noninvasive methods. Clinically, patients usually present with intermittent claudication (IC), which is defined as pain with exertion in the calf. The thigh or the buttock may also be affected. The pain may be described as a dull ache, cramp, or fatigue and is relieved by rest. Notably, <50% of patients with significant occlusive disease are symptomatic and many symptomatic patients present atypically. A method for detection of subclinical PAD and confirmation of symptomatic PAD is available for office use. Briefly, systolic blood pressure (SBP) in both ankles and both arms are obtained with a Doppler probe. The ratio of the SBP at each ankle to the higher SBP in the two arms defines the ankle-brachial index (ABI) for that leg. A significant reduction in flow in the lower extremity will result in a lowering of the systolic ankle pressure, thereby causing a reduction in the ABI. The diagnosis of PAD is made for those with an ABI <0.90 in either leg. ABIs greater than 1.40 are a result of stiff peripheral arteries, and recent evidence suggests that in as many as half the cases such stiff arteries mask underlying PAD.2 Such elevated ABIs are most common in diabetes mellitus (DM) and in chronic kidney disease.
Prevalence The prevalence of PAD depends on the definition used. Estimates of the overall prevalence of PAD based on the diagnosis of IC range from 1.1% to 2.4%.3-5 Older studies limited to those over the age of 60 years estimate the prevalence of IC at 3% to 6%. However, a symptom-based definition of PAD tends to underestimate the prevalence of significant lower extremity artery obstructive disease, since most cases of PAD are asymptomatic or atypically symptomatic.5 For example, in those with PAD using ABI criteria, only 6.3% reported symptoms of IC in the Rotterdam study. When the definition of PAD is based on the presence of subclinical (i.e., the ABI alone) and clinical disease, the overall prevalence of PAD is about 6.1%, or 7.1 million Americans (Fig. 33-1).6 Prevalence rates have been reported to vary somewhat by ethnicity. Both male and female African Americans have the highest
296
TREATMENT OF HYPERTENSION FOR THOSE WITH PERIPHERAL ARTERY DISEASE, 300 Treatment Principles, 300 Nonpharmacologic Treatment, 300 Pharmacologic Therapy, 300 CONCLUSIONS, 301 REFERENCES, 301
rates, followed by Hispanics, Native Americans, non-Hispanic whites, and Asian Americans.6,7 Within each ethnicity, the rates are higher in men and increase exponentially with age, such that the prevalence roughly doubles during each decade of life. Individuals with coronary heart disease (CHD) have a high prevalence of PAD. In a 1995 study, 22% of subjects with angiographically documented CHD had lower extremity vascular occlusive disease using the ABI or plethysmography, with the prevalence of PAD correlating with the severity of CHD. In a more recent study, 40% of hospitalized subjects with a history of CHD had concomitant PAD.8
Risk Factors The risk factors for IC are, in general, similar to those for an abnormal ABI. In the Framingham Offspring Study, every 10-year increase in age was associated with over 2.5-times higher risk for PAD after adjustment for the standard risk factors.4 Similar results were found in the National Health and Nutrition Examination Survey (NHANES), 1999-2000.7 The risk for PAD in African Americans is twice that of non-Hispanic whites and has been reported to be independent of traditional cardiovascular disease (CVD) risk factors.9 Of the major risk factors for CVD, DM, cigarette smoking, and hypertension (HTN) have the largest magnitude of associations with PAD. Individuals with DM have two to four times the risk7,10 of PAD compared with those without DM, whereas an impaired fasting glucose has been associated with a 20% increase in risk after adjustment for other CVD risk factors. The risk associated with cigarette smoking ranges from 2.0 to 4.5.4,7 High serum cholesterol is also associated with an increased risk, but these associations have not always been statistically significant. However, individuals with familial hypercholesterolemia have a substantially higher prevalence of PAD than controls. The risk of PAD in those with documented CHD is over twofold compared with those without this condition.4 In addition, a diagnosis of PAD in those with CHD has been associated with a 2.5-times higher risk for CVD morbidity. The relationship between the ABI and cardiovascular risk factors is nonlinear and may be described as a backward J - or U -shape.11 That is, the prevalence and/or mean values of risk factors such as cigarette smoking, fasting plasma glucose, and waist circumference are highest in those with an ABI <0.9, lowest for those with an ABI 1.0 to 1.39, and intermediate in those >1.4. This “stiff artery,” high-ABI group is also characterized by a high prevalence of individuals with type 2 DM as well as markers for this condition, such as fasting serum insulin levels and body mass index.
3 3 Peripheral Artery Disease in Hypertension Michael H. Criqui and Matthew A. Allison
EPIDEMIOLOGY OF PERIPHERAL ARTERY DISEASE, 296 Prevalence, 296 Risk Factors, 296 Outcomes, 297 CAUSES OF PERIPHERAL ARTERY DISEASE, 297 HYPERTENSION AS A CONTRIBUTING FACTOR TO PERIPHERAL ARTERY DISEASE, 297 Intermittent Claudication Prevalence, 297 Ankle-Brachial Index Prevalence, 297
Peripheral Artery Disease Prevalence by Multiple Noninvasive Tests, 298 Peripheral Artery Disease Prevalence by Angiography, 298 Incidence Studies, 299 Peripheral Artery Disease Progression, 299 Randomized Control Trials, 299 Outcomes Studies of Those with Peripheral Artery Disease and Hypertension, 300 Conclusions, 300
Epidemiology of Peripheral Artery Disease Peripheral artery disease (PAD) is a chronic disease of the large conduit arteries in the lower extremities primarily caused by a significant atherosclerotic burden resulting in luminal obstruction. This condition is often associated with considerable functional limitations.1 The clinical diagnosis of PAD can be confirmed using noninvasive methods. Clinically, patients usually present with intermittent claudication (IC), which is defined as pain with exertion in the calf. The thigh or the buttock may also be affected. The pain may be described as a dull ache, cramp, or fatigue and is relieved by rest. Notably, <50% of patients with significant occlusive disease are symptomatic and many symptomatic patients present atypically. A method for detection of subclinical PAD and confirmation of symptomatic PAD is available for office use. Briefly, systolic blood pressure (SBP) in both ankles and both arms are obtained with a Doppler probe. The ratio of the SBP at each ankle to the higher SBP in the two arms defines the ankle-brachial index (ABI) for that leg. A significant reduction in flow in the lower extremity will result in a lowering of the systolic ankle pressure, thereby causing a reduction in the ABI. The diagnosis of PAD is made for those with an ABI <0.90 in either leg. ABIs greater than 1.40 are a result of stiff peripheral arteries, and recent evidence suggests that in as many as half the cases such stiff arteries mask underlying PAD.2 Such elevated ABIs are most common in diabetes mellitus (DM) and in chronic kidney disease.
Prevalence The prevalence of PAD depends on the definition used. Estimates of the overall prevalence of PAD based on the diagnosis of IC range from 1.1% to 2.4%.3-5 Older studies limited to those over the age of 60 years estimate the prevalence of IC at 3% to 6%. However, a symptom-based definition of PAD tends to underestimate the prevalence of significant lower extremity artery obstructive disease, since most cases of PAD are asymptomatic or atypically symptomatic.5 For example, in those with PAD using ABI criteria, only 6.3% reported symptoms of IC in the Rotterdam study. When the definition of PAD is based on the presence of subclinical (i.e., the ABI alone) and clinical disease, the overall prevalence of PAD is about 6.1%, or 7.1 million Americans (Fig. 33-1).6 Prevalence rates have been reported to vary somewhat by ethnicity. Both male and female African Americans have the highest
296
TREATMENT OF HYPERTENSION FOR THOSE WITH PERIPHERAL ARTERY DISEASE, 300 Treatment Principles, 300 Nonpharmacologic Treatment, 300 Pharmacologic Therapy, 300 CONCLUSIONS, 301 REFERENCES, 301
rates, followed by Hispanics, Native Americans, non-Hispanic whites, and Asian Americans.6,7 Within each ethnicity, the rates are higher in men and increase exponentially with age, such that the prevalence roughly doubles during each decade of life. Individuals with coronary heart disease (CHD) have a high prevalence of PAD. In a 1995 study, 22% of subjects with angiographically documented CHD had lower extremity vascular occlusive disease using the ABI or plethysmography, with the prevalence of PAD correlating with the severity of CHD. In a more recent study, 40% of hospitalized subjects with a history of CHD had concomitant PAD.8
Risk Factors The risk factors for IC are, in general, similar to those for an abnormal ABI. In the Framingham Offspring Study, every 10-year increase in age was associated with over 2.5-times higher risk for PAD after adjustment for the standard risk factors.4 Similar results were found in the National Health and Nutrition Examination Survey (NHANES), 1999-2000.7 The risk for PAD in African Americans is twice that of non-Hispanic whites and has been reported to be independent of traditional cardiovascular disease (CVD) risk factors.9 Of the major risk factors for CVD, DM, cigarette smoking, and hypertension (HTN) have the largest magnitude of associations with PAD. Individuals with DM have two to four times the risk7,10 of PAD compared with those without DM, whereas an impaired fasting glucose has been associated with a 20% increase in risk after adjustment for other CVD risk factors. The risk associated with cigarette smoking ranges from 2.0 to 4.5.4,7 High serum cholesterol is also associated with an increased risk, but these associations have not always been statistically significant. However, individuals with familial hypercholesterolemia have a substantially higher prevalence of PAD than controls. The risk of PAD in those with documented CHD is over twofold compared with those without this condition.4 In addition, a diagnosis of PAD in those with CHD has been associated with a 2.5-times higher risk for CVD morbidity. The relationship between the ABI and cardiovascular risk factors is nonlinear and may be described as a backward J - or U -shape.11 That is, the prevalence and/or mean values of risk factors such as cigarette smoking, fasting plasma glucose, and waist circumference are highest in those with an ABI <0.9, lowest for those with an ABI 1.0 to 1.39, and intermediate in those >1.4. This “stiff artery,” high-ABI group is also characterized by a high prevalence of individuals with type 2 DM as well as markers for this condition, such as fasting serum insulin levels and body mass index.