Albert J. Belanger

Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons

BACKGROUND Low serum thyrotropin concentrations are a sensitive indicator of hyperthyroidism but can also occur in persons who have no clinical manifestations of the disorder. We studied whether low serum thyrotropin concentrations in clinically euthyroid older persons are a risk factor for subsequent atrial fibrillation. METHODS We studied 2007 persons (814 men and 1193 women) 60 years of age or older who did not have atrial fibrillation in order to determine the frequency of this arrhythmia during a 10-year follow-up period. The subjects were classified according to their serum thyrotropin concentrations: those with low values (< or = 0.1 mU per liter; 61 subjects); those with slightly low values (> 0.1 to 0.4 mU per liter; 187 subjects); those with normal values (> 0.4 to 5.0 mU per liter; 1576 subjects); and those with high values (> 5.0 mU per liter; 183 subjects). RESULTS During the 10-year follow-up period, atrial fibrillation occurred in 13 persons with low initial values for serum thyrotropin, 23 with slightly low values, 133 with normal values, and 23 with high values. The cumulative incidence of atrial fibrillation at 10 years was 28 percent among the subjects with low serum thyrotropin values (< or = 0.1 mU per liter), as compared with 11 percent among those with normal values; the age-adjusted incidence of atrial fibrillation was 28 per 1000 person-years among those with low values and 10 per 1000 person-years among those with normal values (P = 0.005). After adjustment for other known risk factors, the relative risk of atrial fibrillation in elderly subjects with low serum thyrotropin concentrations, as compared with those with normal concentrations, was 3.1 (95 percent confidence interval, 1.7 to 5.5; P < 0.001). The 10-year incidence of atrial fibrillation in the groups with slightly low and high serum thyrotropin values was not significantly different from that in the group with normal values. CONCLUSIONS Among people 60 years of age or older, a low serum thyrotropin concentration is associated with a threefold higher risk that atrial fibrillation will develop in the subsequent decade.

Epidemiology of heart failure

Analysis of 34 years of follow-up of Framingham Study data provides clinically relevant insights into the prevalence, incidence, secular trends, prognosis, and modifiable risk factors for the occurrence of heart failure in a general population sample. Heart failure was found to be highly prevalent, affecting about 1% of persons in their 50s and rising progressively with age to afflict 10% of persons in their 80s. The annual incidence also increased with age, from about 0.2% in persons 45 to 54 years, to 4.0% in men 85 to 94 years, with the incidence approximately doubling with each decade of age. Women lagged slightly behind men in incidence at all ages. Male predominance was because of a higher rate of coronary heart disease, which confers a fourfold increased risk of heart failure. Heart failure, once manifest, was highly lethal, with 37% of men and 33% of women dying within 2 years of diagnosis. The 6-year mortality rate was 82% for men and 67% for women, which corresponded to a death rate fourfold to eightfold greater than that of the general population of the same age. Sudden death was a common mode of exitus and accounted for 28% of the cardiovascular deaths in men and 14% in women with heart failure. Hypertension and coronary disease were the predominant causes for heart failure and accounted for more than 80% of all clinical events. Factors reflecting deteriorating cardiac function were associated with a substantial increase in risk of overt heart failure. These include low vital capacity, sinus tachycardia, and ECG evidence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Left Atrial Size and the Risk of Stroke and Death The Framingham Heart Study

BACKGROUND The medical literature contains conflicting reports on the association of left atrial (LA) enlargement with risk of stroke. The relation of LA size to risk of stroke and death in the general population remains largely unexplored. METHODS AND RESULTS Subjects 50 years of age and older from the Framingham Heart Study were studied to assess the relations between echocardiographic LA size and risk of stroke and death. During 8 years of follow-up, 64 of 1371 (4.7%) men and 73 of 1728 (4.2%) women sustained a stroke, and 296 (21.6%) men and 271 (15.7%) women died. Sex-specific Cox proportional-hazards models were adjusted for age, hypertension, diabetes, atrial fibrillation, smoking, ECG left ventricular (LV) hypertrophy, and congestive heart failure or myocardial infarction. After multivariable adjustment, for every 10-mm increase in LA size, the relative risk of stroke was 2.4 in men (95% CI, 1.6 to 3.7) and 1.4 in women (95% CI, 0.9 to 2.1); the relative risk of death was 1.3 in men (95% CI, 1.0 to 1.5) and 1.4 in women (95% CI, 1.1 to 1.7). Adjusting for ECG LV mass/height attenuated the relation of LA size to stroke and death. CONCLUSIONS After multivariable adjustment, LA enlargement remained a significant predictor of stroke in men and death in both sexes. The relation of LA enlargement to stroke and death appears to be partially mediated by LV mass.

Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy.

BACKGROUND During the past half-century, the ECG has been used extensively for the diagnosis of left ventricular hypertrophy. Persons with ECG evidence of left ventricular hypertrophy are at increased risk for the development of cardiovascular disease. METHODS AND RESULTS Subjects from the Framingham Heart Study with ECG evidence of left ventricular hypertrophy were eligible for this investigation if they were free of cardiovascular disease and did not have complete bundle-branch block or Wolff-Parkinson-White syndrome. Logistic regression analyses of pooled biennial examinations were used to determine risk for cardiovascular disease as a function of baseline voltage (sum of R wave in aVL plus S wave in V3) and repolarization and as a function of serial changes in these ECG features of hypertrophy. The eligible sample consisted of 274 men (mean age, 60 years) and 250 women (mean age, 64 years) who contributed 2660 person-examinations. During follow-up, there were 269 new cardiovascular events. Compared with subjects in the first quartile of voltage at baseline, the age-adjusted odds ratio for cardiovascular disease among subjects in the fourth quartile was 3.08 (95% confidence interval [CI], 1.87 to 5.07) in men and 3.29 (95% CI, 1.78 to 6.09) in women. Compared with a normal repolarization pattern, the presence of severe repolarization abnormalities was associated with an age-adjusted odds ratio of 5.84 (95% CI, 3.55 to 9.62) in men and 2.47 (95% CI, 1.38 to 4.42) in women. Subjects with a serial decline in voltage were at lower risk for cardiovascular disease than were those with no serial change (men: odds ratio after adjusting for age and baseline voltage, 0.46; 95% CI, 0.26 to 0.84; women: odds ratio, 0.56; 95% CI, 0.30 to 1.04). In contrast, those with a serial increase in voltage were at greater risk for cardiovascular disease (men: odds ratio, 1.86; 95% CI, 1.14 to 3.03; women: odds ratio, 1.61; 95% CI, 0.91 to 2.84). Compared with those with no serial change, an improvement in repolarization was associated with a marginally significant reduction in cardiovascular risk in men (odds ratio after adjusting for age and baseline repolarization, 0.45; 95% CI, 0.20 to 1.01). Worsening of repolarization was associated with increased risk for cardiovascular disease in both sexes (men: odds ratio, 1.89; 95% CI, 1.05 to 3.40; women: odds ratio, 2.02; 95% CI, 1.07 to 3.81). CONCLUSIONS The results of this investigation suggest that regression of ECG features of left ventricular hypertrophy confers an improvement in risk for cardiovascular disease, whereas serial worsening imposes increased risk. The benefits to be derived from regression of left ventricular hypertrophy must be confirmed in other clinical settings.

Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study.

BACKGROUND AND PURPOSE We sought to modify existing sex-specific health risk appraisal functions (profile functions) for the prediction of first stroke that better assess the effects of the use of antihypertensive medication. METHODS Health risk appraisal functions were previously developed from the Framingham Study cohort. These functions were Cox proportional hazards regression models relating age, systolic blood pressure, diabetes mellitus, cigarette smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy by electrocardiogram, and the use of antihypertensive medication to the occurrence of stroke. Closer examination of the data indicated that antihypertensive therapy effect is present only for systolic blood pressures between 110 and 200 mm Hg. Adjustments to the regressions to better fit the observed data were developed and tested for statistical significance and goodness-of-fit of the model residuals. RESULTS Modified functions more consistent with the data were developed, and, from these, tables to evaluate 10-year risk of first stroke were computed. CONCLUSIONS The stroke profile can be used for evaluation of the risk of stroke and suggestion of risk factor modification to reduce risk. The effect of antihypertensive therapy in the evaluation of stroke risk can now be better evaluated.

Influence of heart rate on mortality among persons with hypertension: the Framingham Study.

Previous studies have shown positive associations between heart rate and both all-cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension.

Variability of Body Weight and Health Outcomes in the Framingham Population

BACKGROUND Fluctuation in body weight is a common phenomenon, due in part to the high prevalence of dieting. In this study we examined the associations between variability in body weight and health end points in subjects participating in the Framingham Heart Study, which involves follow-up examinations every two years after entry. METHODS The degree of variability of body weight was expressed as the coefficient of variation of each subjects measured body-mass-index values at the first eight biennial examinations during the study and on their recalled weight at 25 years of age. Using the 32-year follow-up data, we analyzed total mortality, mortality from coronary heart disease, and morbidity due to coronary heart disease and cancer in relation to intraindividual variation in body weight, including only end points that occurred after the 10th biennial examination. We used age-adjusted proportional-hazards regression for the data analysis. RESULTS Subjects with highly variable body weights had increased total mortality (P = 0.005 for men, P = 0.01 for women), mortality from coronary heart disease (P = 0.009 for men, P = 0.009 for women), and morbidity due to coronary heart disease (P = 0.0009 for men, P = 0.006 for women). Using a multivariate analysis that also controlled for obesity, trends in weight over time, and five indicators of cardiovascular risk, we found that the positive associations between fluctuations in body weight and end points related to mortality and coronary heart disease could not be attributed to these potential confounding factors. The relative risks of these end points in subjects whose weight varied substantially, as compared with those whose weight was relatively stable, ranged from 1.27 to 1.93. CONCLUSIONS Fluctuations in body weight may have negative health consequences, independent of obesity and the trend of body weight over time.

Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Framingham study

During the tenth biennial examination, 1315 Framingham study participants free of cardiovascular disease had fibrinogen measured along with other major cardiovascular risk factors including cigarette smoking. The fibrinogen values were significantly higher in smokers than in nonsmokers, increased with the amount smoked in each sex, and exsmokers had values as low as those of nonsmokers. Over 10 years of follow-up, 165 men and 147 women developed cardiovascular disease, the risk in both sexes increasing progressively in relation to antecedent fibrinogen values over the 180 to 450 mg/dl range. Risk gradients for cardiovascular disease in men diminished with advancing age. In men, risk of cardiovascular disease was related to cigarette smoking. This was true in the multivariate case taking all standard risk factors into account. As for fibrinogen, the impact diminished with advancing age. Regression coefficients were actually larger in the multivariate than in the univariate case because of a negative correlation between smoking and blood pressure. Fibrinogen contributed to cardiovascular disease, risk taking into account both cigarette smoking and other risk factors. When fibrinogen is added to the multivariate model for prediction of cardiovascular disease the coefficient for smoking becomes much reduced and is no longer statistically significant. However, each independently contributed to risk in cross-sectional analysis. These data provide another mechanism whereby cigarette smoking influences the occurrence of atherocardiovascular disease and also another reason for prohibiting cigarette use.

Incidence of dementia and probable Alzheimer's disease in a general population The Framingham Study

objective: To determine the incidence of dementia and Alzheimers disease (AD) in a general population sample. Background: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. Methods: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. Results: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. Conclusions: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years.

Secular trends in the prevalence of atrial fibrillation: The Framingham study

Abstract An increasing prevalence of AF recently noted in hospital discharge data has not been verified in a population-based sample. We determined the prevalence of AF from 1968 to 1989 in the Framingham Study cohort aged 65 to 84 years. AF prevalence was evaluated by sex and in the presence of VHD, prior MI, and CHF. AF prevalence increased significantly in men overall, but not in women, and in men with and without VHD and MI, but not CHF. In men with prior MI, age-adjusted prevalence rose from 4.9% to 17.4% ( p = 0.001). Multivariate analysis confirmed the increase in AF prevalence in men, when age, valve disease, and prior MI are taken into account. The basis for the increased AF prevalence in men is unexplained but may relate to recent improved MI survival. In an aging U.S. population this trend raises the concern of future increases in stroke incidence.