[show abstract][hide abstract] ABSTRACT: To compare implications of Angina Pectoris (AP) and Intermittent Claudication (IC) as indicators of clinical atherosclerosis in other vascular territories.
Prospective cohort study of cardiovascular disease (CVD) in 5,209 men and women of Framingham, MA, aged 28-62 years at enrollment in 1948-1951, who received biennial examinations during the first 36 years of follow-up. Comparative 10-year incidence of subsequent atherosclerotic CVD in participants with IC and AP relative to a reference sample free of CVD was determined.
On follow-up, 95 CVD events occurred in 186 participants with IC and 206 of 413 with AP. After age, sex, and risk-factor adjustment, the proportion acquiring other CVD was 34.0% for IC and 43.4% for AP. Relative to the reference sample, those with IC had a 2.73-fold higher age and sex-adjusted 10-year hazard of CVD (95% CI 2.21, 3.38) and for AP was 3.17 (95% CI 2.73, 3.69). CVD hazard ratios remained more elevated for AP and statistically significant after standard risk factor adjustment. Risk factors accounted for more of the excess CVD risk associated with IC (34.8%) than AP (9.5%).
AP is as useful as IC as a hallmark of diffuse atherosclerotic CVD and an indication for comprehensive preventive measures.
Journal of Clinical Epidemiology 06/2008; 61(9):951-7. · 5.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Information is limited regarding the absolute and relative risk of cardiovascular disease in persons with high-normal blood pressure (systolic pressure of 130 to 139 mm Hg, diastolic pressure of 85 to 89 mm Hg, or both).
We investigated the association between blood-pressure category at base line and the incidence of cardiovascular disease on follow-up among 6859 participants in the Framingham Heart Study who were initially free of hypertension and cardiovascular disease.
A stepwise increase in cardiovascular event rates was noted in persons with higher baseline blood-pressure categories. The 10-year cumulative incidence of cardiovascular disease in subjects 35 to 64 years of age who had high-normal blood pressure was 4 percent (95 percent confidence interval, 2 to 5 percent) for women and 8 percent (95 percent confidence interval, 6 to 10 percent) for men; in older subjects (those 65 to 90 years old), the incidence was 18 percent (95 percent confidence interval, 12 to 23 percent) for women and 25 percent (95 percent confidence interval, 17 to 34 percent) for men. As compared with optimal blood pressure, high-normal blood pressure was associated with a risk-factor-adjusted hazard ratio for cardiovascular disease of 2.5 (95 percent confidence interval, 1.6 to 4.1) in women and 1.6 (95 percent confidence interval, 1.1 to 2.2) in men.
High-normal blood pressure is associated with an increased risk of cardiovascular disease. Our findings emphasize the need to determine whether lowering high-normal blood pressure can reduce the risk of cardiovascular disease.
New England Journal of Medicine 12/2001; 345(18):1291-7. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV(1), FVC, and FEV(1)/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV(1), FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions.
American Journal of Respiratory and Critical Care Medicine 12/2001; 164(9):1655-9. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors examined mammography use according to family cancer history and identified predictors of recent use (<or=2 years). Framingham Offspring Study participants in Framingham, Massachusetts, aged 40-79 years, completed a breast health questionnaire in 1996-1997. The study sample of women included 141 with a first-degree relative with breast cancer, 221 with a mother or sister(s) with other cancers, and 331 with a mother and sister(s) who participate in the Framingham Heart Study and did not report a history of cancer. Stepwise logistic regression analysis was used to identify predictors of recent mammography use. Among women with a family breast cancer history, 98% reported mammography use compared with 95% of other women. Recent mammography use was higher in women with a family breast cancer history (93%) compared with women with a family history of other cancer (80%) and women without a family history of cancer (84%) (p = 0.004). Odds ratios and 95% confidence intervals for significant predictors of recent mammography use were as follows: family history of breast cancer, 3.2 (95% confidence interval (CI): 1.4, 7.7); recent clinical breast examination, 17.4 (95% CI: 9.2, 32.8); and smoking, 0.4 (95% CI: 0.2, 0.7). Mammography use was high among women with a family breast cancer history.
American Journal of Epidemiology 11/2001; 154(10):916-23. · 4.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.
American Journal of Respiratory and Critical Care Medicine 09/2001; 164(6):933-8. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Data from the Third National Health and Nutrition Examination Survey, phase 2 (1991 to 1994), indicate that among hypertensive individuals in the United States, 53.6% are treated and only 27.4% are controlled to goal levels. We sought to determine whether poor hypertension control is due to lack of systolic or diastolic blood pressure control, or both. We studied Framingham Heart Study participants examined between 1990 and 1995 and determined rates of control to systolic goal (<140 mm Hg), diastolic goal (<90 mm Hg), or both (systolic <140 and diastolic <90 mm Hg). Of 1959 hypertensive subjects (mean age 66 years, 54% women), 32.7% were controlled to systolic goal, 82.9% were controlled to diastolic goal, and only 29.0% were controlled to both. Among the 1189 subjects who were receiving antihypertensive therapy (60.7% of all hypertensive subjects), 49.0% were controlled to systolic goal, 89.7% were controlled to diastolic goal, and only 47.8% were controlled to both. Thus, poor systolic blood pressure control was overwhelmingly responsible for poor rates of overall control to goal. Covariates associated with lack of systolic control in treated subjects included older age (OR for age 61 to 75 years, 2.43, 95% CI 1.79 to 3.29; OR for age >75 years, 4.34, 95% CI 3.10 to 6.09), left ventricular hypertrophy (OR 1.63, 95% CI 1.04 to 2.54), and obesity (OR for body mass index >/=30 versus <25 kg/m(2), 1.49, 95% CI 1.08 to 2.06). In this community-based sample of middle-aged and older subjects, overall rates of hypertension control were remarkably similar to those in the Third National Health and Nutrition Examination Survey. Poor blood pressure control was overwhelmingly due to lack of systolic control, even among treated subjects. Therefore, clinicians and policymakers should place greater emphasis on the achievement of goal systolic levels in all hypertensive patients, especially those who are older or obese or have target organ damage.
[show abstract][hide abstract] ABSTRACT: Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study.
We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP (P<0.001). Plasma viscosity was positively related to SBP (P=0.008) and DBP (P=0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex.
These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.
[show abstract][hide abstract] ABSTRACT: Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency.
Little is known about the prevalence of cardiovascular disease (CVD) and associated risk factors in individuals with mild renal insufficiency (RI). Furthermore, the long-term outcomes associated with mild RI in the community have not been described.
Serum creatinine (SCr) was measured in 6233 adult participants of the Framingham Heart Study (mean age 54 years, 54% women). Mild RI was defined as SCr 136 to 265 micromol/liter (1.5 to 3.0 mg/dl) in men and 120 to 265 micromol/liter (1.4 to 3.0 mg/dl) in women. The lower limits for mild RI were defined by the sex-specific 95th percentile SCr values in a healthy subgroup of our sample. The upper limit for mild RI was chosen to exclude those subjects with more advanced renal failure. Cox proportional hazards analyses were used to determine the relationship of baseline RI to CVD and all-cause mortality.
At baseline, 8.7% of men (N = 246) and 8.0% of women (N = 270) had mild RI. Nineteen percent of the subjects with mild RI had prevalent CVD. During 15 years of follow-up, there were 1000 CVD events and 1406 deaths. In women, mild RI was not associated with increased risk for CVD events [hazards ratio (HR) 1.04, 95% CI, 0.79 to 1.37] or all-cause mortality (HR 1.08, 95% CI, 0.87 to 1.34). In men, mild RI showed no significant associations with CVD events (HR 1.17, 95% CI, 0.88 to 1.57), but it was associated with all-cause mortality in age-adjusted (HR 1.42, 95% CI, 1.12 to 1.79) and multivariable adjusted (HR 1.31, 95% CI, 1.02 to 1.67) analyses.
Mild RI in the community is common and is associated with a high prevalence of CVD. The association of RI with risk for adverse outcomes is strongly related to coexisting CVD and CVD risk factors.
Kidney International 01/2000; 56(6):2214-9. · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are stratified into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (> or =1 associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease).
To examine the prevalence of risk groups and blood pressure stages in a community-based sample.
We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups.
In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group A, 59.3% were in group B, and 38.2% were in group C. In the high-normal or hypertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended.
These results provide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice.
Archives of Internal Medicine 11/1999; 159(18):2206-12. · 11.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Short-term (<30 day) mortality after Q-wave myocardial infarction (MI) has declined over the decades, but it is unclear if rates of long-term sequelae after Q-wave MI have improved.
In 546 Framingham Heart Study subjects (388 men with a mean age of 60 years; 158 women with a mean age of 69 years) with an initial recognized Q-wave MI from 1950 through 1989, we investigated time trends in risk for coronary heart disease (CHD) death (n=199), all-cause mortality (n=287), reinfarction (n=108), and congestive heart failure (CHF; n=121). With 1950 through 1969 as the reference period, hazards ratios (HRs) for these outcomes were determined for the 1970s and 1980s. Trend analyses across the 3 time periods were performed for each outcome. Compared with the 1950 through 1969 reference period, the HRs for CHD death were lower in subsequent decades (1970 through 1979: HR, 0.69; 95% CI, 0.49 to 0.98; 1980 through 1989: HR, 0.48; 95% CI, 0.33 to 0.72). All-cause mortality also declined (1970 through 1979: HR, 0.70; 95% CI, 0.0.52 to 0.94; 1980 through 1989: HR, 0.59; 95% CI, 0.43 to 0.81). There were no significant temporal changes in the risks for recurrent MI or CHF.
Substantial reductions in risk of CHD death and all-cause mortality occurred over these 4 decades, coincident with improvements in post-MI therapies. The absence of a decline in CHF incidence may be due to improved post-MI survival of individuals with depressed left ventricular systolic function who are at high risk for CHF.
[show abstract][hide abstract] ABSTRACT: The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure into stages on the basis of both systolic (SBP) and diastolic (DBP) blood pressure levels. When a disparity exists between SBP and DBP stages, patients are classified into the higher stage ("up-staged"). We evaluated the effect of disparate levels of SBP and DBP on blood pressure staging and eligibility for therapy. We examined 4962 Framingham Heart Study subjects between 1990 and 1995 and determined blood pressure stages on the basis of SBP alone, DBP alone, or both. After the exclusion of subjects on antihypertensive therapy (n=1306), 3656 subjects (mean age 58+/-13 years; 55% women) were eligible. In this sample, 64.6% of subjects had congruent stages of SBP and DBP, 31.6% were up-staged on the basis of SBP, and 3.8% on the basis of DBP; thus, SBP alone correctly classified JNC-VI stage in approximately 96% (64.6%+31.6%) of the subjects. Among subjects >60 years of age, SBP alone correctly classified 99% of subjects; in those </=60 years old, SBP alone correctly classified 95%. Of 1488 subjects with high-normal blood pressure or hypertension, who were potentially eligible for drug therapy, 13.0% had congruent elevations of SBP and DBP, 77.7% were up-staged on the basis of SBP, and 9.3% were up-staged on the basis of DBP; SBP alone correctly classified 91%, whereas DBP alone correctly classified only 22%. SBP elevation out of proportion to DBP is common in middle-aged and older persons. SBP appears to play a greater role in the determination of JNC-VI blood pressure stage and eligibility for therapy. Given these results, combined with evidence from hypertension treatment trials, future guidelines might consider a greater role for SBP than for DBP in determining the presence of hypertension, risk of cardiovascular events, eligibility for therapy, and benefits of treatment.
[show abstract][hide abstract] ABSTRACT: Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study.
Classic mitral-valve prolapse was defined as superior displacement of the mitral leaflets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm.
A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild.
In a community based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low.
New England Journal of Medicine 08/1999; 341(1):1-7. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is evolving evidence that heart rate (HR) is genetically determined. Heart rate variability (HRV) measured by power spectral analysis provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HR and HRV only partially explain their variability in the population. The purpose of this study was to assess the heritability of HR and HRV and estimate the contribution of genetic factors to their variance.
Subjects who underwent ambulatory recordings at a routine examination were eligible; subjects with congestive heart failure, coronary artery disease, diabetes mellitus, and those taking cardioactive medications were excluded. We analyzed high-frequency power, low-frequency power, very low-frequency power, total power, low-frequency/high-frequency ratio, and the standard deviation of normal R-R intervals from 2-hour continuous ECG recordings. Heritability analysis was done by studying correlations between siblings (n=682, in 291 sibships, 517 pairs) and between spouse pairs (n=206 pairs) after adjusting for important covariates. Results from separate models were combined to estimate the components of variance attributable to measured covariates, additive genetic effects (heritability), and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21 to 0.26) compared with spouses (0.01 to 0.19). The measured covariates in general accounted for 13% to 40% of the total phenotypic variance, whereas genetic factors accounted for 13% to 23% of the variation among HR and HRV measures.
Heritable factors may explain a substantial proportion of the variance in HR and HRV. These results highlight the contribution of genetic versus environmental factors to autonomic nervous system activity.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to assess the relative proportions of normal versus impaired left ventricular (LV) systolic function among persons with congestive heart failure (CHF) in the community and to compare their long-term mortality during follow-up.
Several hospital-based investigations have reported that a high proportion of subjects with CHF have normal LV systolic function. The prevalence and prognosis of CHF with normal LV systolic function in the community are not known.
We evaluated the echocardiograms of 73 Framingham Heart Study subjects with CHF (33 women, 40 men, mean age 73 years) and 146 age- and gender-matched control subjects (nested case-control study). Impaired LV systolic function was defined as an LV ejection fraction (LVEF) <0.50.
Thirty-seven CHF cases (51%) had a normal LVEF; 36 (49%) had a reduced LVEF. Women predominated in the former group (65%), whereas men constituted 75% of the latter group. During a median follow-up of 6.2 years, CHF cases with normal LVEF experienced an annual mortality of 8.7% versus 3.0% for matched control subjects (adjusted hazards ratio = 4.06, 95% confidence interval 1.61 to 10.26). Congestive heart failure cases with reduced LVEF had an annual mortality of 18.9% versus 4.1% for matched control subjects (adjusted hazards ratio = 4.31, 95% confidence interval 1.98 to 9.36).
Normal LV systolic function is often found in persons with CHF in the community and is more common in women than in men. Although CHF cases with normal LVEF have a lower mortality risk than cases with reduced LVEF, they have a fourfold mortality risk compared with control subjects who are free of CHF.
Journal of the American College of Cardiology 06/1999; 33(7):1948-55. · 14.09 Impact Factor