[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. DOI:10.1164/ajrccm.164.9.2010122 · 13.00 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. DOI:10.1093/aje/154.10.916 · 5.23 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: 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: Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SBP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension.
BP data from exercise testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SBP >/=140 mm Hg or DBP >/=90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SBP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SBP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SBP (chi2, 23.4 in men and 34.7 in women) and DBP (chi2, 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (chi2, 16.4 in men and 6.1 in women) and recovery SBP (chi2, 6.5 in men and 2.1 in women) responses.
An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SBP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension.
[Show abstract][Hide abstract] ABSTRACT: Heart rate variability (HRV) is a useful noninvasive tool to assess cardiac autonomic function. The purpose of this study was to (1) compare measures of HRV between hypertensive and normotensive subjects and (2) examine the role of HRV as a predictor of new-onset hypertension. The first 2 hours of ambulatory ECG recordings obtained from 931 men and 1111 women attending a routine examination at the Framingham Heart Study were processed for HRV. Three time-domain and 5 frequency-domain variables were studied: standard deviation of normal RR intervals (SDNN), percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds, square root of the mean of squared differences between adjacent normal RR intervals, total power (0.01 to 0.40 Hz), high frequency power (HF, 0.15 to 0.40 Hz), low frequency power (LF, 0.04 to 0.15 Hz), very low frequency power (0.01 to 0.04 Hz), and LF/HF ratio. On cross-sectional analysis, HRV was significantly lower in hypertensive men and women. Among 633 men and 801 women who were normotensive at baseline (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg and not receiving antihypertensive treatment), 119 men and 125 women were newly hypertensive at follow-up 4 years later. After adjustment for factors associated with hypertension, multiple logistic regression analysis revealed that LF was associated with incident hypertension in men (odds ratio per SD decrement [OR], 1.38; 95% confidence interval [CI], 1.04 to 1.83) but not in women (OR, 1.12; 95% CI, 0.86 to 1.46). SDNN, HF, and LF/HF were not associated with hypertension in either sex. HRV is reduced in men and women with systemic hypertension. Among normotensive men, lower HRV was associated with greater risk for developing hypertension. These findings are consistent with the hypothesis that autonomic dysregulation is present in the early stage of hypertension.
[Show abstract][Hide abstract] ABSTRACT: Several studies have examined the association of blood pressure (BP) after myocardial infarction (MI) with a risk for adverse outcome; however, few studies have investigated prognosis after MI as a function of BP before MI. Our goal was to examine the relation of antecedent hypertension to risk of adverse outcomes after initial MI. From 1967 to 1990, 404 subjects followed at the Framingham Heart Study developed an initial MI. These subjects were classified on the basis of preinfarction BP into normotensive (BP<140/90 mm Hg and not receiving antihypertensive treatment; n=118), stage I-untreated hypertension (BP 140 to 159/90 to 99 mm Hg; n=89), and stage II to IV or treated hypertension (BP > or =160/100 mm Hg or treated hypertension; n=197). Cox models were used to adjust for age, sex, smoking, glucose intolerance, total cholesterol, and prior cardiovascular disease. Antecedent hypertension was related to risk of adverse outcome after MI. Compared with normotensive individuals, stage II to IV hypertensives were at increased risk for reinfarction (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.20 to 4.04). A similar but nonsignificant association was seen in stage I hypertensives (HR, 1.91; 95% CI, 0.97 to 3.77). Stage II to IV hypertensives were at increased risk for all-cause mortality compared with normotensive persons (HR, 1.45; 95% CI, 1.07 to 1.98). Thus, even after MI, a history of antecedent hypertension remains predictive of adverse outcome. These findings are consistent with beneficial effects of BP control in primary and secondary prevention settings. Effective BP control may both reduce the risk for an initial MI and improve outcome in the event that an MI occurs.
[Show abstract][Hide abstract] ABSTRACT: Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population.
The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86).
The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.
[Show abstract][Hide abstract] ABSTRACT: Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample.
In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking beta-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise ("chronotropic response index"). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease (P <.01). Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age, ST-segment response, physical activity, and traditional coronary disease risk factors (adjusted hazard ratio, 1.75; 95% confidence interval, 1.11 to 2.74; P=.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality (P=.04) and coronary heart disease incidence (P=.0003). The chronotropic response index also was predictive of total mortality (P=.05) and incident coronary heart disease (P=.001) after adjusting for age and other risk factors.
An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.