Albert Oberman

Effect of Type 2 Diabetes Mellitus on Left Ventricular Geometry and Systolic Function in Hypertensive Subjects Hypertension Genetic Epidemiology Network (HyperGEN) Study

Background—Type 2 diabetes is a cardiovascular risk factor. It remains to be elucidated in a large, population-based sample whether diabetes is associated with changes in left ventricular (LV) structure and systolic function independent of obesity and systolic blood pressure (BP). Methods and Results—Among 1950 hypertensive participants in the HyperGEN Study without overt coronary heart disease or significant valve disease, 20% (n=386) had diabetes. Diabetics were more likely to be women, black, older, and have higher BMI and waist/hip ratio than were nondiabetics. After adjustment for age and sex, diabetics had higher systolic BP, pulse pressure, and heart rate; lower diastolic BP; and longer duration of hypertension than nondiabetics. LV mass and relative wall thickness were higher in diabetic than nondiabetic subjects independent of covariates. Compared with nondiabetic hypertensives, diabetics had lower stress-corrected midwall shortening, independent of covariates, without difference in LV EF. Insulin levels and insulin resistance were higher in non–insulin-treated diabetics (n=195) than nondiabetic (n=1439) subjects (both P <0.01). Insulin resistance positively but weakly related to LV mass and relative wall thickness. Conclusions—In a relatively healthy, population-based sample of hypertensive adults, type 2 diabetes was associated with higher LV mass, more concentric LV geometry, and lower myocardial function, independent of age, sex, body size, and arterial BP.

Cardiovascular risk factors in young adults: The CARDIA baseline monograph

Gary R. Cutter, PhD*(1), Gregory L. Burke, MD (2), Alan R. Dyer, PhD (3), Gary D. Friedman, MD (4), Joan E. Hilner, MPH, MA, RD (5), Glenn H. Hughes, PhD (6), Stephen B. Hulley, MD (7), David R. Jacobs Jr., PhD (2), Kiang Liu, PhD (3), Teri A. Manolio, MD, MHS (8), Albert Oberman, MD (9), Laura L. Perkins, PhD (5), Peter J. Savage, MD (8), Joyce R. Serwitz, MEd (5), Stephen Sidney, MD (4), Lynne E. Wagenknecht, Dr PH (5)

Effect of Antihypertensives on Sexual Function and Quality of Life: The TAIM Study

OBJECTIVE To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies. DESIGN Multicenter, randomized, placebo-controlled clinical trial. SETTING Three university-based tertiary care centers. PATIENTS Patients (697) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight. INTERVENTION Patients were stratified by clinical center and race and were randomly assigned to one of three diets (usual, low-sodium and high-potassium, weight loss) and one of three agents (placebo, chlorthalidone, and atenolol). MEASUREMENTS Changes in measures of sexual problems, distress, and well-being after 6 months of therapy were analyzed. MAIN RESULTS Low-dose chlorthalidone and atenolol produced few side effects, except in men. Erection-related problems worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%; CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of life most, reducing total physical complaints (P less than 0.001) and increasing satisfaction with health (P less than 0.001). Total physical complaints decreased in 57% to 76% of patients depending on drug and diet group, and were markedly decreased by weight loss. CONCLUSION In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men.

Differences in Left Ventricular Structure Between Black and White Hypertensive Adults The Hypertension Genetic Epidemiology Network Study

The degree to which ethnic differences in left ventricular structure among hypertensive adults are independent of clinical and hemodynamic factors remains uncertain. We assessed whether left ventricular mass and geometry differ between black and white hypertensives after accounting for differences in such factors. Our study group comprised 1060 black and 580 white hypertensive participants free of valvular or coronary disease in a population-based cohort. Blood pressure was measured during a clinic visit and echocardiography was performed using standardized protocols. After controlling for clinical and hemodynamic parameters (cardiac index, peripheral resistance index, and pulse pressure/ stroke index), both left ventricular mass and relative wall thickness were higher in blacks than whites (173.9±30.9 versus 168.3±24.3 grams, P =0.006, and 0.355±0.055 versus 0.340±0.055 grams, P <0.001). Similarly, the adjusted risk of having left ventricular hypertrophy, whether indexed by height2.7 or by body surface area, was greater for blacks than for whites (odds ratio: 1.80; 95% CI: 1.29 to 2.51; and odds ratio: 2.50; 95% CI: 1.58 to 3.96, respectively), and this was also true for concentric geometry (odds ratio: 2.28; 95% CI: 1.22 to 4.25). Further adjustment for relatedness in this genetic epidemiological study did not attenuate these differences. Our findings confirm the strong association between black ethnicity and increased left ventricular mass and relative wall thickness in hypertensive adults and demonstrate that these differences are independent of standard clinical and hemodynamic parameters. Whether such differences relate to distinct ambulatory pressure profiles or an ethnic propensity to cardiac hypertrophy requires further investigation.

Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study.

The association of insulin with cardiovascular disease (CVD) may be mediated in part by the associations of insulin with CVD risk factors, particularly blood pressure and serum lipids. These associations were examined in 4576 black and white young adults in the CARDIA Study. Fasting insulin level was correlated in univariate analysis with systolic blood pressure (r = 0.16), diastolic blood pressure (r = 0.13), triglycerides (r = 0.27), total cholesterol (r = 0.10), high density lipoprotein (HDL) cholesterol (r = -0.25), and low density lipoprotein (LDL) cholesterol (r = 0.14), and with age, sex, race, glucose, body mass index, alcohol intake, cigarette use, physical activity, and treadmill duration (all p less than 0.0001). After adjustment for these covariates, insulin remained positively associated with blood pressure, triglycerides, total and LDL cholesterol, and apolipoprotein B and was negatively associated with HDL, HDL2 and HDL3 cholesterol, and apolipoprotein A-I in all four race-sex groups. Higher levels of fasting insulin are associated with unfavorable levels of CVD risk factors in young adults; these associations, though relatively small, can be expected to increase the risk of atherosclerosis. Demonstration of these relationships in a large, racially diverse, healthy population suggests that insulin may be an important intermediate risk factor for CVD in a broad segment of the U.S. population.

Late results of surgical and medical therapy for patients with coronary artery disease and depressed left ventricular function

Late survival and freedom from myocardial infarction were determined for 192 patients with coronary artery disease and depressed left ventricular ejection fraction at rest (less than or equal to 35%) determined by biplane angiography who were evaluated between 1970 and 1977. Seventy-seven patients had coronary artery bypass grafting and 115 patients were treated medically and were considered surgical candidates. The medical and surgical groups were comparable in all baseline characteristics examined except frequency of three vessel disease and angina pectoris, which occurred in a significantly greater percent of the surgically treated patients (p less than 0.01). Only three medically treated patients (2.6%) underwent coronary bypass grafting in the follow-up period. Seven year actuarial survival was 63% in the surgical and 34% in the medical group (p less than 0.001). Ninety-three percent of patients in the surgical group and 81% of those in the medical group were free of nonfatal myocardial infarction (p = 0.01), and 62 and 33%, respectively, were alive and free of myocardial infarction (p less than 0.001) at 7 years. Significant differences in survival favoring surgical treatment were observed for the subsets of patients with an ejection fraction of 25% or less (p = 0.0002) and 26 to 35% (p = 0.01), and for the subsets with three vessel coronary disease (p less than 0.001), normal left ventricular end-diastolic volume (less than or equal to 100 ml/m2) (p = 0.005) and elevated end-diastolic volume (greater than 100 ml/m2)(p = 0.001). After adjustment for other important prognostic variables, the type of treatment remained significant in predicting the relative risk (medical to surgical) of mortality at 5 and 7 years (2.58 and 2.12, respectively). These data corroborate the trends observed in several randomized trials of medical and surgical therapy in patients with abnormal left ventricular function. If hospital mortality for coronary artery bypass grafting is less than 5%, substantial benefit can be anticipated for the majority of patients with depressed ventricular function.

Effects of a prescribed supervised exercise program on mortality and cardiovascular morbidity in patients after a myocardial infarction: The National Exercise and Heart Disease Project∗☆

This study enrolled 651 men with myocardial infarction in five participating centers in a randomized 3 year clinical trial of the effects of prescribed supervised exercise. The subjects, aged to 30 to 64 years, were screened for eligibility 2 to 36 months after their qualifying myocardial infarction. The men in the exercise group pursued intensive exercise in the laboratory for 8 weeks and then in a gymnasium for 34 months. The experience of the exercise group was more favorable than that of the control group in most of the comparisons made. The cumulative 3 year total mortality rate was 7.3 percent for the control group and 4.6 percent for the exercise group; the 3 year rate for recurrent myocardial infarction was 7.0 and 5.3 percent, respectively. Mortality rates in the two groups did not differ significantly, but the data were consistent with an assumption of substantial benefit from exercise. Adjustment for small differences in baseline variables by multivariate methods did not materially alter the estimate of effect of exercise. Certain subgroups showed a greater benefit from exercise.

Angiotensinogen Genotype, Sodium Reduction, Weight Loss, and Prevention of Hypertension: Trials of Hypertension Prevention, Phase II

The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2x2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10). In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the GG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17). Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension.

Natural history of angina pectoris

Abstract An understanding of the natural history of angina pectoris is crucial to decision making in the management of patients with this disease. Early investigations suggested a highly variable annual mortality rate, ranging from 2.5 to 9 percent. These studies clearly pointed to the association of certain electrocardiographic changes, hypertension, cardiac enlargement and congestive heart failure with increased mortality. Several recent studies based on findings at coronary arteriography indicate a high degree of correlation between the extent of coronary atherosclerotic occlusive disease and the likelihood of early death. A combination of data from several laboratories indicates that if only one of the three major coronary arterial branches (left anterior descending, left circumflex or right) is significantly stenosed, the annual mortality rate will be approximately 2 percent of the cohort. If two of the three major arteries are stenosed, the rate will be approximately 7 percent, and if all three arteries are stenosed, it will be approximately 11 percent. Some data suggest that these mortality figures based on the extent of atherosclerotic occlusive disease are importantly modulated by the extent of ventricular myocardial impairment as reflected by cardiac enlargement or symptoms of congestive heart failure.

Chronic congestive heart failure in coronary artery disease: clinical criteria.

Congestive heart failure is a frequent and important manifestation of cardiovascular disease, but no uniform clinical criteria are available for use in epidemiologic studies. To develop diagnostic criteria, we related pertinent clinical findings to physiologic measures of left ventricular function in patients with coronary artery disease. When left ventricular end diastolic pressure or arteriovenous oxygen difference was used as the physiologic criterion, the following variables contributed significant (P less than 0.01) information: heart volume, ventricular gallop, heart rate, and blood pressure. The most reliable and valid set of descriptors determined in one group was tested in a second group of 1306 patients who had been followed for 6 to 36 months after initial evaluation. The validity of the descriptors was confirmed, and patients identified as having heart failure by these criteria experienced a worse survival rate (P less than 0.001). These criteria characterize patients likely to have impaired left ventricular function and a greater risk of death.