- Email: [email protected]
Comparison of quinapril versus atenolol: effects on blood pressure and cardiac mass after renal transplantation
Comparison of Quinapril Versus Atenolol: Effects on Blood Pressure and Cardiac Mass After Renal Transplantation Barbara Suwelack,
MD,
Ulf Gerhardt, MD, Martin Hausberg, and Helge Hohage, MD
ardiovascular disease is still the major cause of death in patients with chronic renal insufficiency C and end-stage renal disease. Angiotensin-converting 1
enzyme inhibitors have been shown to slow the progression of chronic renal failure and act as potent antihypertensive drugs in patients after renal transplantation.2 The impact of angiotensin-converting enzyme inhibitors on left ventricular (LV) morphology and function in hypertensive renal transplant recipients has not been established. This double-blind, randomized study compares the structural and functional cardiac changes of quinapril versus atenolol administered to hypertensive kidney transplant recipients. •••
Thirty-one renal allograft recipients in whom arterial hypertension developed 6 to 12 weeks after transplantation volunteered to participate in the present randomized, double-blind study by giving their informed consent. Only patients with cyclosporine immunosuppression and stable graft function (serum creatinine ⬍2.5 mg/dl) were included. The groups had no statistically significant differences in height, weight, age, or duration of hemodialysis before renal transplantation (Table I). In both groups, an arterial blood pressure (BP) measurement (Dinamap device), echocardiographic examination, and blood sampling were conducted within 24 hours before application of the first dose of the antihypertensive treatment and also after 24-month follow-up. After randomization, 14 patients received atenolol, and the other 17 patients were treated with quinapril. A standardized scheme was used as follows: Antihypertensive treatment was begun immediately after detection of arterial hypertension. Target diastolic BP was 90 mm Hg. The initial quinapril dose was 5 mg/day, and the initial atenolol dose 12.5 mg/day. If target BP could not be achieved with the initial dose, a stepwise increase up to 40 mg (range 10 to 20) of quinapril or up to 100 mg (range 25 to 50) of atenolol was conducted. If the maximal dose of quinapril or atenolol monotherapy was not sufficient to achieve target BP, we added 40 mg (up to 80 mg if necessary) of furosemide. A calcium antagonist was added in case the double therapy was insufficient. We used a 2.5-MHz sector transducer (SSA-270A Toshiba Corporation, Shimoishigami, Otawara, Tochigi-Ken, Japan). All 2-dimensional, M-mode, and Doppler echocardiographic examinations were perFrom Medical Department D, University of Mu¨nster, Mu¨nster, Germany. Dr. Suwelack’s address is: Medizinische Poliklinik, AlbertSchweitzer-Strasse 33, D-48149 Mu¨nster, Germany. E-mail: [email protected]. Manuscript received November 29, 1999; revised manuscript received and accepted March 23, 2000. ©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 September 1, 2000
MD,
Karl Heinz Rahn,
MD,
formed by the same experienced senior sonographer in patients in the partial left decubitus position. The 2-dimensional– guided M-mode measurements were obtained according to the recommendations of the American Society of Echocardiography.3 All of the patients were in sinus rhythm. Only data with highquality Doppler signals were used for analysis. Patients with severe aortic or mitral regurgitations or with heart rates ⬎100 beats/min were excluded from the study. The LV internal diameter, the thickness of the ventricular septum, and the posterior LV wall were determined by M mode according to the widely accepted criteria.3 These parameters were used in an anatomically validated formula to calculate LV mass.4 Measurements of the LV mass were divided by body surface area to obtain LV mass index. For measurement of mitral inflow velocity, the pulsed Doppler sample volume was positioned at the level of the mitral annulus from an apical 4-chamber view, parallel to the assumed direction of diastolic inflow. The peak velocity of early (E) and late (A) diastolic filling was measured and the ratio of late-toearly diastolic flow velocity (E/A ratio) was calculated. Furthermore, the midwall fractional shortening was calculated by using a previously validated equation.5 Statistical analysis was performed using the computer software Excel (Microsoft Inc.,), Winstat (Fitch software Inc., Staufen, Germany), and SPSS statistical package 4.0 (SPSS Inc., Chicago, Illinois). Data are expressed as mean ⫾ SEM. Student’s t test was used to calculate the levels of statistical significance. A multiple stepwise regression analysis was used to determine possible associations of LV mass index with BP, medication, heart rate, carotid vessel wall properties, laboratory findings, anthropometric data, and so forth. The basic laboratory findings in quinapril-treated (n ⫽ 17) and atenolol-treated (n ⫽ 14) kidney transplant recipients were comparable (Table I). Both groups were well matched, especially in graft function (s-creatinine), parathyroid hormone, cholesterol blood concentrations, and medication (cyclosporine A whole blood levels, corticoid daily intake). The E/A ratio increased only in the quinapril group (⫹0.11; p ⬍0.05), whereas it decreased by 0.03 (p ⬎0.05 vs start of treatment) in the atenolol group. The difference between the E/A ratio alterations of the quinapril and the atenolol groups (Table II) was statistically significant (p ⬍0.05). A significant (p ⬍0.05 vs start of treatment) decrease of the LV mass index (LVMI) from the beginning to end (24 months) of the drug 0002-9149/00/$–see front matter PII S0002-9149(00)01024-9
583
LV mass 3.5 years after renal transplantation.7 Until now, there are no data available on possible cardiac alAtenolol Quinapril terations associated with angioten(n ⫽ 14) (n ⫽17) sin-converting enzyme inhibitors in Age (yrs) 47 ⫾ 2.3 43 ⫾ 3.1 renal allograft recipients. Height (cm) 174.1 ⫾ 2.4 172.0 ⫾ 2.9 The main finding of the present Initial weight (kg) 69.5 ⫾ 3.5 65.5 ⫾ 3.4 study is the reduction in LV mass Duration of hemodialysis (mo) 35.4 ⫾ 5.0 36.5 ⫾ 7.9 index in patients treated with Initial serum creatinine (mg/dl) 1.4 ⫾ 0.1 1.4 ⫾ 0.1 End-serum creatinine (mg/dl) 1.4 ⫾ 0.1 1.5 ⫾ 0.1 quinapril after renal transplantation. End iPTH (ng/L) 83.4 ⫾ 19.2 94.5 ⫾ 20.8 The echocardiographically observed Initial cholesterol (mg/dl) 256.1 ⫾ 13.5 245.1 ⫾ 13.0 cardiac alterations in renal allograft End-cholesterol (mg/dl) 270.8 ⫾ 14.6 262.4 ⫾ 11.2 recipients were not correlated to the Initial cyclosporine A whole blood level (ng/ml) 92.3 ⫾ 6.4 89.9 ⫾ 4.9 amount of BP reduction in the End-cyclosporine A whole blood level (ng/ml) 95.8 ⫾ 8.6 87.9 ⫾ 7.9 Initial corticoid dose (mg/d) 12.0 ⫾ 1.0 12.0 ⫾ 1.2 present investigation. BP reduction End-corticoid dose (mg/d) 7.0 ⫾ 0.5 7.7 ⫾ 0.4 in the atenolol-treated group was twice as high as that in the quinapriliPTH ⫽ intact parathyroid hormone. treated group. A reduction in LV mass, however, was detected only in the latter group. Furthermore, a multiple stepwise regression analysis TABLE II BP, LV Mass, E/A Ratio, and Fractional Shortening in Quinapril Versus Atenolol-treated Patients Before (initial) and 24 Months After (end) Renal showed that arterial BP did not corTransplantation relate with cardiac mass reduction. In 1 previous study without any signifAtenolol Quinapril (n ⫽ 14) (n ⫽ 17) icant BP reduction in patients treated with lisinopril, no specific effect of 2 Initial LVMI (g/m ) 149.1 ⫾ 11.1 151.9 ⫾ 8.0 this antihypertensive drug on regresEnd LVMI (g/m2) 134.8 ⫾ 10.0 136.1 ⫾ 5.5 ⌬LVMI (g/m2) 14.1 ⫾ 10.1 15.8 ⫾ 7.7† sion of myocardial hypertrophy or Initial LV-FS (%) 38.3 ⫾ 1.7 38.5 ⫾ 1.4 improvement in LV diastolic funcEnd LV-FS (%) 36.3 ⫾ 1.5 39.3 ⫾ 1.7 tion could be detected within a † ⌬FS (%) ⫺2 ⫾ 1.1 0.8 ⫾ 1.7 6-month period in patients with Initial E/A ratio 1.11 ⫾ 0.09 1.08 ⫾ 0.08 chronic hemodialysis.8 End E/A ratio 1.08 ⫾ 0.08 1.19 ⫾ 0.08 ⌬E/A ratio ⫺0.03 ⫾ 0.07 0.11 ⫾ 0.06*† The functional cardiac parameters Initial MAP (mm Hg) 110.0 ⫾ 1.4† 113.4 ⫾ 1.5 such as the E/A ratio, however, are End MAP (mm Hg) 99.3 ⫾ 2.8 108.9 ⫾ 2.8* known to evolve independently from ⌬MAD (mm Hg) 10.7 ⫾ 3.4 4.5 ⫾ 2.9*† LV hypertrophy.8 E/A ratio reflects *p ⬍0.05; †p ⬍0.05 (initial vs end). an impaired relaxation as a predomFS ⫽ fractional shortening; MAD ⫽ mean aterial diastolic pressure; MAP ⫽ mean arterial pressure; MI inant pattern of LV diastolic dys⫽ mass index. function.9 In the present study, a significant improvement in LV diastolic comparison (atenolol vs quinapril) was observed only function was detected in addition to LV mass reducin the quinapril group (Table II). The fractional short- tion in quinapril-treated renal allograft recipients. ening increased slightly (p ⬎0.05) in the quinapril We conclude that in hypertensive renal allograft group from the start to the end of the 24-month folrecipients, quinapril in contrast to atenolol prolow-up, but decreased (p ⬍0.05) in the atenolol group vides a sufficient reduction in LV hypertrophy and (Table II). The differences between the groups cona concomitant improvement in LV diastolic carcerning these alterations were not statistically significant. Table II also shows the mean arterial BP in renal diac relaxation, and these effects occur indepentransplant recipients receiving quinapril and atenolol dently from BP reduction. antihypertensive treatment. As expected, a statistically Acknowledgment: The perfect technical assistance significant (p ⬍0.05) reduction in arterial BP was achieved in both groups. The BP decrease was signif- of S. Raunitschke is gratefully acknowledged. icantly (p ⬍0.05) more pronounced in the atenolol group (10.7 ⫾ 3.4 vs 4.5 ⫾ 2.9 mm Hg with 1. Levey AS, Eknoyan G. Cardiovascular disease in chronic renal disease. quinapril). Nephrol Dial Transplant 1999;14:828 – 833. TABLE I Anthropometric and Laboratory Data of Kidney Transplant Recipients Receiving Atenolol Versus Quinapril Treatment
•••
The course of cardiac hypertrophy in renal transplant recipients, however, has been controversial. Although 1 study provided evidence that LV mass decreases substantially after renal transplantation without concomitant improvement in LV diastolic function,6 another investigation reported an increased 584 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
2. Hausberg M, Barenbrock M, Hohage H, Muller S, Heidenreich S, Rahn KH. ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients. Hypertension 1999;33:862– 866. 3. Sahn DJ, DeMaria A, Kisslo J, Weyman A. The committee on M-mode Standardization of the American Society of Echocardiography: recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–1083. 4. Devereux RB, Reicheck N. Echocardiographic determination of left ventricular mass in man. Circulation 1977;55:613– 618.
SEPTEMBER 1, 2000
5. de Simone G, Devereux RB, Roman MJ, Ganau A, Saba PS, Alderman MH. Assessment of left ventricular function by the midwall fractional shortening/endsystolic stress relation in human hypertension. J Am Coll Cardiol 1994;23:1444 – 1451. 6. Himelman RB, Landzberg JS, Simonson JS, Amend W, Bouchard A, Merz R, Schiller NB. Cardiac consequences of renal transplantation: changes in left ventricular morphology and function. J Am Coll Cardiol 1988;12:915–923. 7. Hu¨ting J. Course of left ventricular hypertrophy and function en end-stage renal disease after renal transplantation. J Am Coll Cardiol 1992;70:1481–1484.
8. Rothinger FX, Punzengruber C, Wallner M, Ulbrich W, Pachinger O, Kramar
R, Prischl FC. The influence of ACE-inhibition on myocardial mass and diastolic function in chronic hemodialysis patients with adequate control of blood pressure. Clin Nephrol 1994;42:309 –314. 9. Zabalgoitia M, Rahman SNU, Haley WE, Abochamh DA, Oneschuk L, Merena J, Yarows S, Krause L, Yunis C, Lucas C. Role of left ventricular hypertrophy in diastolic dysfunction in aged hypertensive patients. J Hypertens 1997;15:1175–1179.
Increased Plasma Homocysteine Is an Independent Predictor of New Atherothrombotic Brain Infarction in Older Persons Wilbert S. Aronow,
MD,
Chul Ahn,
meta-analysis showed that plasma homocysteine was an independent risk factor for cerebrovascuA lar disease. Three prospective studies reported that 1
plasma homocysteine was an independent risk factor for stroke.2– 4 These studies were the Framingham Study of elderly men and women,2 a study among British men, mean age 54 years,3 and a study from the Hopkins Lupus Cohort.4 However, 2 prospective studies did not find this association.5,6 These studies were a study of Finnish men and women 40 to 64 years of age5 and a study of US male physicians responding to a survey.6 Atherothrombotic brain infarction (ABI) is mainly a disease of the elderly. One of these 5 prospective studies, the Framingham Study, investigated the association between plasma homocysteine levels and stroke in elderly persons.2 We previously reported an association between plasma homocysteine level and coronary artery disease in 153 older men and in 347 older women.7 We are now reporting 31-month follow-up data showing that plasma homocysteine is an independent risk factor for new ABI in these 500 older persons. •••
We reported that high plasma homocysteine levels and low plasma folate and vitamin B12 levels were associated with a higher prevalence of coronary artery disease in 153 men and in 347 women (mean age 81 ⫾ 9 years [range 60 to 99, median 82]) in a long-term health care facility.7 We investigated in a prospective study the association of plasma homocysteine, folate, and vitamin B12 levels and of other risk factors with the incidence of new ABI in these 500 older men and women. Fasting plasma homocysteine, folate, and vitamin B12 levels were determined as previously described.7 Other risk factors investigated were prior ABI, current cigarette smoking, systemic hypertension, diabetes mellitus, fasting serum total cholesterol, From the Hebrew Hospital Home, Bronx, New York; the Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York; and the Division of Clinical Epidemiology, University of Texas Medical School at Houston, Houston, Texas. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Boulevard, Bronx, New York 10475. Manuscript received February 10, 2000; revised manuscript received and accepted March 22, 2000. ©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 September 1, 2000
PhD,
and Hal Gutstein,
MD
high-density lipoprotein cholesterol, and triglycerides, and obesity. Prior ABI was diagnosed by a neurologist as previously described.8 Hypertension was diagnosed according to the criteria of the Sixth Joint National Committee Report on the Detection, Evaluation, and Treatment of Hypertension.9 Diabetes mellitus was diagnosed according to the American Diabetic Association new criteria.10 The weight and height of each person were correlated with the average height-weight table for persons aged 65 to 94 years.11 A person was considered obese if he or she was ⱖ20% above ideal body weight. Persons were followed for the incidence of new ABI. New ABI was diagnosed by a neurologist when the person experienced a documented sudden, focal neurologic deficit lasting ⬎24 hours in the absence of a known source of embolism, bloody cerebrospinal fluid, known hypercoagulable conditions, or other diseases causing focal brain deficits. ABI was diagnosed if the documented focal neurologic deficit lasted ⬎24 hours and left residual or no residual focal neurologic deficit. A careful neurologic examination was performed in each person for signs of a focal neurologic deficit that conformed to the typical vascular distribution of an ABI. New ABI was also confirmed by computerized axial tomography in 74 of 76 persons (97%). The follow-up period was from the time the baseline data were obtained until the time of new ABI, death from any cause, or the cutoff date for analysis of data. The mean follow-up period was 31 ⫾ 9 months (range 1 to 36). For analyses comparing persons with and without new ABI, chi-square tests were used for dichotomous variables and Student’s t tests for continuous variables (Table I). The stepwise Cox regression model was used to identify significant independent predictors of new ABI (Table II) using the software SAS PROC PHREG (Cary, North Carolina). As a criterion for entering and removing variables into the model, we used p ⫽ 0.05 in the stepwise Cox regression model, which is the default criterion in SAS PROC PHREG. The proportionality hazard assumptions were met in the Cox regression model. 0002-9149/00/$–see front matter PII S0002-9149(00)01025-0
585
MD,
Ulf Gerhardt, MD, Martin Hausberg, and Helge Hohage, MD
ardiovascular disease is still the major cause of death in patients with chronic renal insufficiency C and end-stage renal disease. Angiotensin-converting 1
enzyme inhibitors have been shown to slow the progression of chronic renal failure and act as potent antihypertensive drugs in patients after renal transplantation.2 The impact of angiotensin-converting enzyme inhibitors on left ventricular (LV) morphology and function in hypertensive renal transplant recipients has not been established. This double-blind, randomized study compares the structural and functional cardiac changes of quinapril versus atenolol administered to hypertensive kidney transplant recipients. •••
Thirty-one renal allograft recipients in whom arterial hypertension developed 6 to 12 weeks after transplantation volunteered to participate in the present randomized, double-blind study by giving their informed consent. Only patients with cyclosporine immunosuppression and stable graft function (serum creatinine ⬍2.5 mg/dl) were included. The groups had no statistically significant differences in height, weight, age, or duration of hemodialysis before renal transplantation (Table I). In both groups, an arterial blood pressure (BP) measurement (Dinamap device), echocardiographic examination, and blood sampling were conducted within 24 hours before application of the first dose of the antihypertensive treatment and also after 24-month follow-up. After randomization, 14 patients received atenolol, and the other 17 patients were treated with quinapril. A standardized scheme was used as follows: Antihypertensive treatment was begun immediately after detection of arterial hypertension. Target diastolic BP was 90 mm Hg. The initial quinapril dose was 5 mg/day, and the initial atenolol dose 12.5 mg/day. If target BP could not be achieved with the initial dose, a stepwise increase up to 40 mg (range 10 to 20) of quinapril or up to 100 mg (range 25 to 50) of atenolol was conducted. If the maximal dose of quinapril or atenolol monotherapy was not sufficient to achieve target BP, we added 40 mg (up to 80 mg if necessary) of furosemide. A calcium antagonist was added in case the double therapy was insufficient. We used a 2.5-MHz sector transducer (SSA-270A Toshiba Corporation, Shimoishigami, Otawara, Tochigi-Ken, Japan). All 2-dimensional, M-mode, and Doppler echocardiographic examinations were perFrom Medical Department D, University of Mu¨nster, Mu¨nster, Germany. Dr. Suwelack’s address is: Medizinische Poliklinik, AlbertSchweitzer-Strasse 33, D-48149 Mu¨nster, Germany. E-mail: [email protected]. Manuscript received November 29, 1999; revised manuscript received and accepted March 23, 2000. ©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 September 1, 2000
MD,
Karl Heinz Rahn,
MD,
formed by the same experienced senior sonographer in patients in the partial left decubitus position. The 2-dimensional– guided M-mode measurements were obtained according to the recommendations of the American Society of Echocardiography.3 All of the patients were in sinus rhythm. Only data with highquality Doppler signals were used for analysis. Patients with severe aortic or mitral regurgitations or with heart rates ⬎100 beats/min were excluded from the study. The LV internal diameter, the thickness of the ventricular septum, and the posterior LV wall were determined by M mode according to the widely accepted criteria.3 These parameters were used in an anatomically validated formula to calculate LV mass.4 Measurements of the LV mass were divided by body surface area to obtain LV mass index. For measurement of mitral inflow velocity, the pulsed Doppler sample volume was positioned at the level of the mitral annulus from an apical 4-chamber view, parallel to the assumed direction of diastolic inflow. The peak velocity of early (E) and late (A) diastolic filling was measured and the ratio of late-toearly diastolic flow velocity (E/A ratio) was calculated. Furthermore, the midwall fractional shortening was calculated by using a previously validated equation.5 Statistical analysis was performed using the computer software Excel (Microsoft Inc.,), Winstat (Fitch software Inc., Staufen, Germany), and SPSS statistical package 4.0 (SPSS Inc., Chicago, Illinois). Data are expressed as mean ⫾ SEM. Student’s t test was used to calculate the levels of statistical significance. A multiple stepwise regression analysis was used to determine possible associations of LV mass index with BP, medication, heart rate, carotid vessel wall properties, laboratory findings, anthropometric data, and so forth. The basic laboratory findings in quinapril-treated (n ⫽ 17) and atenolol-treated (n ⫽ 14) kidney transplant recipients were comparable (Table I). Both groups were well matched, especially in graft function (s-creatinine), parathyroid hormone, cholesterol blood concentrations, and medication (cyclosporine A whole blood levels, corticoid daily intake). The E/A ratio increased only in the quinapril group (⫹0.11; p ⬍0.05), whereas it decreased by 0.03 (p ⬎0.05 vs start of treatment) in the atenolol group. The difference between the E/A ratio alterations of the quinapril and the atenolol groups (Table II) was statistically significant (p ⬍0.05). A significant (p ⬍0.05 vs start of treatment) decrease of the LV mass index (LVMI) from the beginning to end (24 months) of the drug 0002-9149/00/$–see front matter PII S0002-9149(00)01024-9
583
LV mass 3.5 years after renal transplantation.7 Until now, there are no data available on possible cardiac alAtenolol Quinapril terations associated with angioten(n ⫽ 14) (n ⫽17) sin-converting enzyme inhibitors in Age (yrs) 47 ⫾ 2.3 43 ⫾ 3.1 renal allograft recipients. Height (cm) 174.1 ⫾ 2.4 172.0 ⫾ 2.9 The main finding of the present Initial weight (kg) 69.5 ⫾ 3.5 65.5 ⫾ 3.4 study is the reduction in LV mass Duration of hemodialysis (mo) 35.4 ⫾ 5.0 36.5 ⫾ 7.9 index in patients treated with Initial serum creatinine (mg/dl) 1.4 ⫾ 0.1 1.4 ⫾ 0.1 End-serum creatinine (mg/dl) 1.4 ⫾ 0.1 1.5 ⫾ 0.1 quinapril after renal transplantation. End iPTH (ng/L) 83.4 ⫾ 19.2 94.5 ⫾ 20.8 The echocardiographically observed Initial cholesterol (mg/dl) 256.1 ⫾ 13.5 245.1 ⫾ 13.0 cardiac alterations in renal allograft End-cholesterol (mg/dl) 270.8 ⫾ 14.6 262.4 ⫾ 11.2 recipients were not correlated to the Initial cyclosporine A whole blood level (ng/ml) 92.3 ⫾ 6.4 89.9 ⫾ 4.9 amount of BP reduction in the End-cyclosporine A whole blood level (ng/ml) 95.8 ⫾ 8.6 87.9 ⫾ 7.9 Initial corticoid dose (mg/d) 12.0 ⫾ 1.0 12.0 ⫾ 1.2 present investigation. BP reduction End-corticoid dose (mg/d) 7.0 ⫾ 0.5 7.7 ⫾ 0.4 in the atenolol-treated group was twice as high as that in the quinapriliPTH ⫽ intact parathyroid hormone. treated group. A reduction in LV mass, however, was detected only in the latter group. Furthermore, a multiple stepwise regression analysis TABLE II BP, LV Mass, E/A Ratio, and Fractional Shortening in Quinapril Versus Atenolol-treated Patients Before (initial) and 24 Months After (end) Renal showed that arterial BP did not corTransplantation relate with cardiac mass reduction. In 1 previous study without any signifAtenolol Quinapril (n ⫽ 14) (n ⫽ 17) icant BP reduction in patients treated with lisinopril, no specific effect of 2 Initial LVMI (g/m ) 149.1 ⫾ 11.1 151.9 ⫾ 8.0 this antihypertensive drug on regresEnd LVMI (g/m2) 134.8 ⫾ 10.0 136.1 ⫾ 5.5 ⌬LVMI (g/m2) 14.1 ⫾ 10.1 15.8 ⫾ 7.7† sion of myocardial hypertrophy or Initial LV-FS (%) 38.3 ⫾ 1.7 38.5 ⫾ 1.4 improvement in LV diastolic funcEnd LV-FS (%) 36.3 ⫾ 1.5 39.3 ⫾ 1.7 tion could be detected within a † ⌬FS (%) ⫺2 ⫾ 1.1 0.8 ⫾ 1.7 6-month period in patients with Initial E/A ratio 1.11 ⫾ 0.09 1.08 ⫾ 0.08 chronic hemodialysis.8 End E/A ratio 1.08 ⫾ 0.08 1.19 ⫾ 0.08 ⌬E/A ratio ⫺0.03 ⫾ 0.07 0.11 ⫾ 0.06*† The functional cardiac parameters Initial MAP (mm Hg) 110.0 ⫾ 1.4† 113.4 ⫾ 1.5 such as the E/A ratio, however, are End MAP (mm Hg) 99.3 ⫾ 2.8 108.9 ⫾ 2.8* known to evolve independently from ⌬MAD (mm Hg) 10.7 ⫾ 3.4 4.5 ⫾ 2.9*† LV hypertrophy.8 E/A ratio reflects *p ⬍0.05; †p ⬍0.05 (initial vs end). an impaired relaxation as a predomFS ⫽ fractional shortening; MAD ⫽ mean aterial diastolic pressure; MAP ⫽ mean arterial pressure; MI inant pattern of LV diastolic dys⫽ mass index. function.9 In the present study, a significant improvement in LV diastolic comparison (atenolol vs quinapril) was observed only function was detected in addition to LV mass reducin the quinapril group (Table II). The fractional short- tion in quinapril-treated renal allograft recipients. ening increased slightly (p ⬎0.05) in the quinapril We conclude that in hypertensive renal allograft group from the start to the end of the 24-month folrecipients, quinapril in contrast to atenolol prolow-up, but decreased (p ⬍0.05) in the atenolol group vides a sufficient reduction in LV hypertrophy and (Table II). The differences between the groups cona concomitant improvement in LV diastolic carcerning these alterations were not statistically significant. Table II also shows the mean arterial BP in renal diac relaxation, and these effects occur indepentransplant recipients receiving quinapril and atenolol dently from BP reduction. antihypertensive treatment. As expected, a statistically Acknowledgment: The perfect technical assistance significant (p ⬍0.05) reduction in arterial BP was achieved in both groups. The BP decrease was signif- of S. Raunitschke is gratefully acknowledged. icantly (p ⬍0.05) more pronounced in the atenolol group (10.7 ⫾ 3.4 vs 4.5 ⫾ 2.9 mm Hg with 1. Levey AS, Eknoyan G. Cardiovascular disease in chronic renal disease. quinapril). Nephrol Dial Transplant 1999;14:828 – 833. TABLE I Anthropometric and Laboratory Data of Kidney Transplant Recipients Receiving Atenolol Versus Quinapril Treatment
•••
The course of cardiac hypertrophy in renal transplant recipients, however, has been controversial. Although 1 study provided evidence that LV mass decreases substantially after renal transplantation without concomitant improvement in LV diastolic function,6 another investigation reported an increased 584 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
2. Hausberg M, Barenbrock M, Hohage H, Muller S, Heidenreich S, Rahn KH. ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients. Hypertension 1999;33:862– 866. 3. Sahn DJ, DeMaria A, Kisslo J, Weyman A. The committee on M-mode Standardization of the American Society of Echocardiography: recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072–1083. 4. Devereux RB, Reicheck N. Echocardiographic determination of left ventricular mass in man. Circulation 1977;55:613– 618.
SEPTEMBER 1, 2000
5. de Simone G, Devereux RB, Roman MJ, Ganau A, Saba PS, Alderman MH. Assessment of left ventricular function by the midwall fractional shortening/endsystolic stress relation in human hypertension. J Am Coll Cardiol 1994;23:1444 – 1451. 6. Himelman RB, Landzberg JS, Simonson JS, Amend W, Bouchard A, Merz R, Schiller NB. Cardiac consequences of renal transplantation: changes in left ventricular morphology and function. J Am Coll Cardiol 1988;12:915–923. 7. Hu¨ting J. Course of left ventricular hypertrophy and function en end-stage renal disease after renal transplantation. J Am Coll Cardiol 1992;70:1481–1484.
8. Rothinger FX, Punzengruber C, Wallner M, Ulbrich W, Pachinger O, Kramar
R, Prischl FC. The influence of ACE-inhibition on myocardial mass and diastolic function in chronic hemodialysis patients with adequate control of blood pressure. Clin Nephrol 1994;42:309 –314. 9. Zabalgoitia M, Rahman SNU, Haley WE, Abochamh DA, Oneschuk L, Merena J, Yarows S, Krause L, Yunis C, Lucas C. Role of left ventricular hypertrophy in diastolic dysfunction in aged hypertensive patients. J Hypertens 1997;15:1175–1179.
Increased Plasma Homocysteine Is an Independent Predictor of New Atherothrombotic Brain Infarction in Older Persons Wilbert S. Aronow,
MD,
Chul Ahn,
meta-analysis showed that plasma homocysteine was an independent risk factor for cerebrovascuA lar disease. Three prospective studies reported that 1
plasma homocysteine was an independent risk factor for stroke.2– 4 These studies were the Framingham Study of elderly men and women,2 a study among British men, mean age 54 years,3 and a study from the Hopkins Lupus Cohort.4 However, 2 prospective studies did not find this association.5,6 These studies were a study of Finnish men and women 40 to 64 years of age5 and a study of US male physicians responding to a survey.6 Atherothrombotic brain infarction (ABI) is mainly a disease of the elderly. One of these 5 prospective studies, the Framingham Study, investigated the association between plasma homocysteine levels and stroke in elderly persons.2 We previously reported an association between plasma homocysteine level and coronary artery disease in 153 older men and in 347 older women.7 We are now reporting 31-month follow-up data showing that plasma homocysteine is an independent risk factor for new ABI in these 500 older persons. •••
We reported that high plasma homocysteine levels and low plasma folate and vitamin B12 levels were associated with a higher prevalence of coronary artery disease in 153 men and in 347 women (mean age 81 ⫾ 9 years [range 60 to 99, median 82]) in a long-term health care facility.7 We investigated in a prospective study the association of plasma homocysteine, folate, and vitamin B12 levels and of other risk factors with the incidence of new ABI in these 500 older men and women. Fasting plasma homocysteine, folate, and vitamin B12 levels were determined as previously described.7 Other risk factors investigated were prior ABI, current cigarette smoking, systemic hypertension, diabetes mellitus, fasting serum total cholesterol, From the Hebrew Hospital Home, Bronx, New York; the Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York; and the Division of Clinical Epidemiology, University of Texas Medical School at Houston, Houston, Texas. Dr. Aronow’s address is: Hebrew Hospital Home, 801 Co-op City Boulevard, Bronx, New York 10475. Manuscript received February 10, 2000; revised manuscript received and accepted March 22, 2000. ©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 September 1, 2000
PhD,
and Hal Gutstein,
MD
high-density lipoprotein cholesterol, and triglycerides, and obesity. Prior ABI was diagnosed by a neurologist as previously described.8 Hypertension was diagnosed according to the criteria of the Sixth Joint National Committee Report on the Detection, Evaluation, and Treatment of Hypertension.9 Diabetes mellitus was diagnosed according to the American Diabetic Association new criteria.10 The weight and height of each person were correlated with the average height-weight table for persons aged 65 to 94 years.11 A person was considered obese if he or she was ⱖ20% above ideal body weight. Persons were followed for the incidence of new ABI. New ABI was diagnosed by a neurologist when the person experienced a documented sudden, focal neurologic deficit lasting ⬎24 hours in the absence of a known source of embolism, bloody cerebrospinal fluid, known hypercoagulable conditions, or other diseases causing focal brain deficits. ABI was diagnosed if the documented focal neurologic deficit lasted ⬎24 hours and left residual or no residual focal neurologic deficit. A careful neurologic examination was performed in each person for signs of a focal neurologic deficit that conformed to the typical vascular distribution of an ABI. New ABI was also confirmed by computerized axial tomography in 74 of 76 persons (97%). The follow-up period was from the time the baseline data were obtained until the time of new ABI, death from any cause, or the cutoff date for analysis of data. The mean follow-up period was 31 ⫾ 9 months (range 1 to 36). For analyses comparing persons with and without new ABI, chi-square tests were used for dichotomous variables and Student’s t tests for continuous variables (Table I). The stepwise Cox regression model was used to identify significant independent predictors of new ABI (Table II) using the software SAS PROC PHREG (Cary, North Carolina). As a criterion for entering and removing variables into the model, we used p ⫽ 0.05 in the stepwise Cox regression model, which is the default criterion in SAS PROC PHREG. The proportionality hazard assumptions were met in the Cox regression model. 0002-9149/00/$–see front matter PII S0002-9149(00)01025-0
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