Shantha Madhavan

Association of the Renin-Sodium Profile with the Risk of Myocardial Infarction in Patients with Hypertension

BACKGROUND To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction.

Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction.

The prognostic value of pretreatment pulse pressure as a predictor of myocardial infarction and the relation of pulse pressure and in-treatment diastolic blood pressure reduction to myocardial infarction were investigated in a union-sponsored systematic hypertension control program. In a prospective study, 2207 hypertensive patients with a pretreatment systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 95 mm Hg grouped according to tertile of pulse pressure (PP1, < or = 46; PP2, 47 to 62; PP3, > or = 63 mm Hg) were further stratified by the degree of diastolic fall: large (L), > or = 18; moderate (M), 7 to 17; small (S), < or = 6 mm Hg. During an average follow-up of 5 years, 132 cardiovascular events (50 myocardial infarctions, 23 strokes) were observed. Myocardial infarction rates per 1000 person-years were positively related to pulse pressure (PP1, 3.5; PP2, 2.9; PP3, 7.5; PP3 versus PP1, P = .02). Wide pulse pressure was identified as a predictor of myocardial infarction (PP3 versus [PP1 + PP2]: relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.2-4.1), controlling for other known risk factors by Cox regression. A curvilinear relation (resembling a J shape) between diastolic fall and myocardial infarction was observed in patients with the widest pulse pressure, PP3 (L, 9.5; M, 3.9; S, 11.2; L versus M: RR = 2.5, 95% CI = 1.0-6.2; S versus M: RR = 2.9, 95% CI = 1.1-8.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum Uric Acid and Cardiovascular Events in Successfully Treated Hypertensive Patients

To determine whether pretreatment and/or in-treatment serum uric acid (SUA) is independently and specifically associated with cardiovascular events in hypertensive patients, we examined the 20-year experience of 7978 mild-to-moderate hypertensive participants in a systematic worksite treatment program. Clinical evaluation and treatment were protocol-directed. SUA was measured at entry and annually thereafter. Subjects were stratified according to gender-specific quartile of baseline SUA. Blood pressures at entry and in-treatment were, respectively, 152.5/95.6 and 138.9/85.4 mm Hg. SUA was normally distributed with a mean of 0.399+/-0.0893 and 0. 321+/-0.0833 mmol/L for men and women, respectively. Subjects with highest SUA were heavier, had greater evidence of cardiovascular disease (CVD), higher systolic blood pressure, higher creatinine, more frequent diuretic use, and lower prevalence of diabetes. During an average follow-up of 6.6 years (52 751 patient-years), 548 CVD events (183 mortal) and 116 non-CVD events occurred. In bivariate analysis, the association of SUA to CVD was more robust in nonwhites than whites and in patients at low versus high CVD risk. In multivariate analysis, CVD incidence was significantly associated with SUA with a hazard ratio of 1.22 (95% confidence interval 1.11 to 1.35), controlling for other known cardiovascular risk factors, including serum creatinine, body mass index, and diuretic use. Despite blood pressure control, SUA levels increased during treatment and were significantly and directly associated with CVD events, independently of diuretic use and other cardiovascular risk factors.

Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I)

BACKGROUND Population-wide restriction of dietary sodium has been recommended. However, little evidence directly links sodium intake to morbidity and mortality. The aim of this study was to assess the relation of sodium intake to subsequent all-cause and cardiovascular-disease (CVD) mortality in a general population. METHODS The first National Health and Nutrition Examination Survey established baseline information during 1971-75 in a representative sample of 20729 US adults (aged 25-75). 11348 underwent medical examination and nutritional examination based on 24 h recall. Two had no data on sodium intake available. Vital status at June 30, 1992, was obtained for the 11346 participants through interview, tracing, and searches of the national death index. Mortality was examined in sex-specific quartiles of sodium intake, calorie intake, and sodium/calorie ratio. Multiple regression analyses were done to assess the relations with mortality. FINDINGS There were 3923 deaths, of which 1970 were due to CVD. All-cause mortality (per 1000 person-years; adjusted for age and sex) was inversely associated with sex-specific quartiles of sodium intake (lowest to highest quartile 23.18 to 19.01, p<0.0001) and total calorie intake (25.03 to 18.40, p<0.0001) and showed a weak positive association with quartiles of sodium/calorie ratio (20.27 to 21.71, p=0.14). The pattern for CVD mortality was similar (sodium 11.80 to 9.60, p<0.0019; calories 12.80 to 8.94, p<0.0002; sodium/calorie ratio 9.73 to 11.35, p=0.017). In Cox multiple regression analysis, sodium intake was inversely associated with all-cause (p=0.0069) and CVD mortality (p=0.086) and sodium/calorie ratio was directly associated with all-cause (p=0.0004) and CVD mortality (p=0.0056). By contrast, calorie intake in the presence of the two measures of sodium intake was not independently associated with mortality (all-cause p=0.86; CVD p=0.74). Analysis restricted to participants with no history of CVD at baseline gave similar results. INTERPRETATION This observational study does not justify any particular dietary recommendation. Specifically, these results do not support current recommendations for routine reduction of sodium consumption, nor do they justify advice to increase salt intake or to decrease its concentration in the diet.

Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men.

A sodium-reduced diet is frequently recommended for hypertensive individuals. To determine the relationship of sodium intake to subsequent cardiovascular disease, we assessed the experience of participants in a worksite-based cohort of hypertensive subjects. The 24-hour urinary excretion of sodium (UNaV), potassium, creatinine, and plasma renin activity was measured in 2937 mildly and moderately hypertensive subjects who were unmedicated for at least 3-4 weeks. Morbidity and mortality in these systematically treated subjects were ascertained. Men and women were stratified according to sex-specific quartiles of UNaV. Subjects in these strata were similar in race, cardiovascular status, and pretreatment and intreatment blood pressure. Subjects with lower UNaV were thinner, excreted less potassium, and had higher plasma renin activity. During an average 3.8 years of follow-up, a total of 55 myocardial infarctions occurred. Myocardial infarction and UNaV were inversely associated in the total population and in men but not in women, who sustained only nine events. In men, age- and race-adjusted myocardial infarction incidence in the lowest versus highest UNaV quartile was 11.5 versus 2.5 (relative risk, 4.3, 95% confidence interval, 1.7-10.6). No association was observed between non-cardiovascular disease mortality (n = 11) and UNaV. There was a significant linear trend in proportions of myocardial infarction by UNaV quartile, with a break point after the lowest UNaV quartile.(ABSTRACT TRUNCATED AT 250 WORDS)

THE ASSOCIATION BETWEEN BIRTHPLACE AND MORTALITY FROM CARDIOVASCULAR CAUSES AMONG BLACK AND WHITE RESIDENTS OF NEW YORK CITY

BACKGROUND Life expectancy is shorter and mortality from cardiovascular disease higher among blacks than among whites in the United States. We studied whether place of birth was associated with mortality from cardiovascular causes among non-Hispanic black and white residents of New York City. METHODS We linked mortality records from 1988 through 1992 with 1990 U.S. census data for New York City. Mortality data for blacks born in the U.S. South and Northeast and in the Caribbean were compared with those for whites born in the Northeast. RESULTS Among blacks, the rates of overall mortality and mortality from cardiovascular causes exceeded those among whites. Among persons born in the Northeast, the rates of death from cardiovascular disease for white men (285 per 100,000), as compared with black men (299), and for white women (155), as compared with black women (165), were similar. However, Southern-born black men and women both had mortality from cardiovascular disease that was substantially higher than that of their counterparts born in the Northeast, and Caribbean-born blacks had rates substantially lower than their Northeastern-born counterparts. The differences among the groups in the rates of death from coronary heart disease were greater than those for death due to stroke or hypertension. In each category defined by age and sex, Caribbean-born blacks had significantly lower rates of death from coronary heart disease than did whites. Black men who were 25 to 44 years of age and were born in the South had a rate of death from coronary heart disease that was 30 percent higher than that of Northeastern-born blacks, and four times that of Caribbean-born blacks of the same sex and age. CONCLUSIONS The higher rate of mortality from cardiovascular causes among blacks, as compared with whites, in New York City masks substantial variation among blacks based on their place of birth.

Plasma renin activity : A risk factor for myocardial infarction in hypertensive patients

To determine whether pretreatment plasma renin activity (PRA), without accompanying 24-h urine sodium, can predict myocardial infarction (MI), the PRA levels of 2,902 hypertensive patients [white (38%), male (65%), median age 55 years], with mean entry blood pressure (BP) of 150/97 mm Hg were examined. During an average 3.6 years follow-up (87% > or = 9 months), there were 55 MIs, 21 strokes, and 16 other cardiovascular disease (CVD) deaths. Classification of PRA levels into 3 renin strata [high (H) PRA > or = 4.5 (n = 354), normal (N) 0.75 to 4.49 (n = 1,622), and low (L) < 0.75 (n = 926) ng/mL/h] yielded subgroups that did not differ in LVH (9% v 11%) or smoking prevalence (26% v 25%) but high versus low PRA subjects included more aged < 55 years (64% v 53%); white (49% v 25%); men (79% v 52%); cholesterol > or = 6.3 mmol/L (33% v 25%); all P values < .01. MI rates per 1,000/year were H: 9.3, N: 5.5, L: 2.5 (H v L, RR = 3.8, 95% CI: 1.7 to 8.4). A similar relationship was seen with total CVD (H: 12.5, N: 9.3, L: 5.2; RR = 2.4, 95% CI: 1.3 to 4.5) and all-cause mortality (H: 7.0, N: 6.2, L: 2.5; RR = 2.8, 95% CI: 1.2 to 6.8) but not CVA (H: 1.6, N: 2.0, L: 1.9). In a Cox survival analysis only renin, age, sex, smoking, LVH, and cholesterol were significantly (P < .02) related to MI occurrence. There was, for every 2 unit increase in PRA, an overall 25% increase in MI incidence. Among hypertensive subjects, PRA level (without urine sodium), is independently and directly associated with the incidence of MI.

Measures of blood pressure and myocardial infarction in treated hypertensive patients.

Objective To identify entry characteristics associated with subsequent myocardial infarction in treated hypertensive patients. Design Nested case-control study and cohort study. Setting and patients The 5730 participants (mean age 53 years; 61% male and 45% Caucasian) were selected from a worksite-based, union-sponsored, systematic hypertension control program from 1973 to 1992. Methods In the case-control study myocardial infarction cases were matched by age, sex, year of entry to the program, years of follow-up and previous treatment status (treated or untreated) with non-event subjects. Baseline clinical and biochemical characteristics were analyzed with regard to the outcome of myocardial infarction, using univariate and multivariate analyses, respectively, in case-control and cohort studies. Results During 5.43 years of follow-up the incidence of myocardial infarction was 6.75/1000 person-years. Univariate analysis indicated that myocardial infarction cases had higher cholesterol level and were more likely to have a previous history of diabetes than controls. The initial systolic blood pressure and pulse pressure of cases were significantly higher than in controls. Logistic regression models indicated that initial pulse pressure, either as a continuous or as a categorical variable, was the only measure of blood pressure independently associated with myocardial infarction after adjustment for other risk factors. Analysis of the experience of the total 5730 as well as 2445 previously untreated patients with a cohort study generated identical results. Conclusion A large pulse pressure difference appears to be the most powerful measure available of initial blood pressure to identify, in advance, those hypertensive patients at greatest risk for a subsequent myocardial infarction.

Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients

BACKGROUND Short-acting calcium antagonists may increase coronary artery morbidity, mortality, and non-cardiovascular complications in hypertensive patients. We assessed whether this association was also true for long-acting calcium antagonists. METHODS We did a case-control study, which was nested within a systematic hypertension control programme for a prospective cohort of 4350 people (first seen 1981-94). Cases (n = 189) were hypertensive patients who had had a first cardiovascular event, including all cardiovascular deaths and hospitalisations, between 1989 and 1995. Controls (n = 189) were individually matched to cases for sex, ethnic origin, age, type of previous antihypertensive treatment, year of entry into the study, and length of follow-up. We collected data on any prescribed drug regimen that was being taken on the event data for cases and on the same date for matched controls. Calcium antagonists were classified by duration of action. FINDINGS Compared with those on beta-blocker monotherapy, patients on long-acting calcium antagonists (n = 136) had no increased risk of a cardiovascular event (adjusted odds ratio 0.76 [95% CI 0.41-1.43]), whereas patients on short-acting calcium antagonists (n = 27) were at significantly greater risk (adjusted odds ratio 3.88 [1.15-13.11], p = 0.029). Among 38 matched pairs who were both on calcium antagonists, the adjusted risk ratio for short-acting versus long-acting was 8.56 (1.88-38.97), p < 0.01. INTERPRETATION Long-acting and short-acting calcium antagonists differ in cardiovascular outcomes. Consistent with earlier findings, the use of short-acting calcium antagonists was associated with increased risk of a cardiovascular event. This finding highlights the need to complete on-going clinical trials so that the relative cardiovascular impact of various antihypertensive agents can be assessed.

Residential segregation and mortality in New York City

The objective of this research was to determine the effect of residential racial segregation on all-cause and cardiovascular disease mortality in New York City. A cross-sectional study of residents in New York City was conducted linking mortality records from 1988 through 1994, to the 1990 United States Census data stratified by zipcode. All-cause and cardiovascular disease mortality rates for non-Hispanic blacks and whites were estimated by zipcode. Zipcodes were aggregated according to the degree of residential segregation (predominantly (> or = 75%) white and black areas) and mortality rates were compared. Multiple regression analysis was used to associate population characteristics with mortality. In New York City, although overall mortality rates of blacks exceed whites, these rates varied substantially by locality according to the pattern of racial segregation. Whites living in the higher (mainly white) socioeconomic areas had lower mortality rates than whites living in predominantly black areas (1473.7 vs 1934.1 for males, and 909.9 vs 1414.7 for females for all-cause mortality). This was true for all age groups. By contrast, elderly blacks living in black areas, despite their less favorable socioeconomic status, had lower mortality rates for all-cause, total cardiovascular disease, and coronary heart disease, than did those living in white areas, even after adjusting for available socioeconomic variables. Racial segregation in residence is independently associated with mortality. Within racially segregated areas, members of the dominant group, for all age, among whites and elderly blacks, enjoy outcomes superior both to members of the minority racial group of their community, and to members of the same race residing in other areas, where they are in the minority, independent of socio-economic status.