Frederick N. Brand

Gout and coronary heart disease: The framingham study☆

The relationship between gout, not associated with the use of diuretics, and the development of coronary heart disease was examined in 5209 subjects originally enrolled in the Framingham Study. Based on 32 years of follow-up, the two year incidence of gout was six times greater in men (3.2/1000) as compared to women (0.5/1000). For both sexes, the incidence of gout showed no clear relationship with age. Among men who never received diuretics, those afflicted by gout, as compared to those without gout, experienced a 60% excess of coronary heart disease (95% confidence limits, 1.1-2.2), primarily attributed to a two fold excess of angina pectoris (95% confidence limits, 1.2-3.1). Although gout was usually associated with other atherogenic risk factors, control of systolic blood pressure, total cholesterol, alcohol intake, body mass index, and diabetes failed to alter the effect of gout on the preceding coronary events in men. For women, there were no significant associations between gout and coronary heart disease. We conclude that gout, unrelated to the intake of diuretics, imparts an additional risk of coronary heart disease in men, unexplained by clinically measured risk factors.

Hematocrit and the risk of cardiovascular disease—The Framingham Study: A 34-year follow-up

We examined the relationship between the risk of CVD mortality and morbidity and HCT over a period of 34 years of follow-up in the 5209 men and women in the Framingham cohort. There was an increased risk of all-cause death as well as morbidity and mortality due to CVD in subjects with HCT values in the highest quintile. There was no evidence of a decrease risk of CVD in men with lower than median HCT values, and women actually showed increased risk of CVD events with lower HCT values, indicating a J- or U-shaped relationship between HCT and CVD events. The impact of HCT on CVD events appears to differ for different age groups and by sex. HCT is significantly related to the incidence of CVD, including CHD, MI, angina pectoris, stroke, and IC in younger men. In younger women, HCT is related to the incidence of CVD, CHD, MI and mortality from CVD and CHD. A negative association with CHF incidence and stroke death is noted in elderly women. These results support the hypothesis that HCT is an important risk factor for some CVD events, an association that merits further investigation.

Diabetes, Intermittent Claudication, and Risk of Cardiovascular Events: The Framingham Study

The impact of diabetes on intermittent claudication was examined in 1813 men and 2504 women with 34-yr follow-up data in the Framingham study. For both sexes, diabetes was associated with a two- to threefold excess risk of intermittent claudication compared with its absence. A pronounced excess risk was also observed in subjects on oral hypoglycemic therapy and in women receiving insulin. Although diabetes was often associated with an atherogenic-risk profile, controlling for age and several concomitant risk factors failed to eliminate the association with intermittent claudication. Those who developed both intermittent claudication and diabetes were at an especially high risk of incident cardiovascular events. In women, the risk of coronary heart disease, stroke, and cardiac failure was increased 3–4 times when diabetes and intermittent claudication occurred together compared with when either condition existed alone. In diabetic men, the presence of intermittent claudication doubled the risk of stroke, and cardiac failure was ∼3 times more likely in subjects with both conditions compared with either alone. We conclude that diabetes is an important risk factor for intermittent claudication, which in turn confers a serious prognosis for subsequent cardiovascular outcomes in the patient with diabetes.

Temporal Patterns of Stroke Onset: The Framingham Study

BACKGROUND AND PURPOSE Several studies have shown stroke onset to vary by season, day of the week, and time of day. These temporal patterns, which may provide insights into pathogenesis, were found mainly in clinical series, which can be subject to selection bias. To obtain a less distorted picture of stroke onset, we examined the month and season, day of the week, time, and place stroke occurred in a community-based cohort. METHODS Over a 40-year period of surveillance of the Framingham Study cohort of 5070 people aged 30 to 62 years and free of stroke and cardiovascular disease at entry, 637 completed initial strokes occurred. Month, season, day of the week, time of day, and place of occurrence of stroke were ascertained systematically and related prospectively to stroke incidence, subtype, and gender. RESULTS Winter was the peak season for cerebral embolic strokes. Significantly more stroke events occurred on Mondays than any other day, particularly for working men. For intracerebral hemorrhages, a third happened on Mondays in both genders. The time of day when strokes most frequently occurred was between 8 AM and noon. This pattern was true for all stroke subtypes. This pattern persisted when individuals whose onset occurred while sleeping or on awakening were excluded. Stroke in general occurred more at home, with hemorrhagic strokes occurring outside the home and cerebral embolisms in the hospital more than other subtypes. CONCLUSIONS Temporal patterns of stroke onset were observed for season, day of the week, time of day, and place in a community-based population. These findings suggest that there are periods of increased risk of stroke that may be amenable to preventive strategies.

Epidemiology of some peripheral arterial findings in diabetic men and women: Experiences from the Framingham study

PURPOSE AND PATIENTS AND METHODS The purpose of this study was to determine the relationship between diabetes and the development of some peripheral arterial findings--carotid and femoral bruits and nonpalpable pedal pulse--and acute cardiovascular events in 1,196 men and 1,582 women based on 20-year follow-up data in the Framingham Study. RESULTS For both men and women without diabetes, the incidence of carotid bruits and nonpalapble pedal pulses increased significantly with age (p less than 0.05) without any apparent male predominance. In contrast, diabetic men and women were at an elevated risk of each peripheral arterial condition that was not appreciably different across age groups. Compared with women without diabetes, those with diabetes experienced nearly a twofold excess of femoral bruits (p less than 0.05) and a 50% excess of nonpalpable pedal pulses (p less than 0.01). Among men, diabetes nearly doubled the risk of carotid bruits (p less than 0.05). Those who had both diabetes and symptoms of peripheral arterial disease were at especially high risk of incident cardiovascular events. In particular, nonpalpable pedal pulses were associated with more than a twofold excess of coronary heart disease (p less than 0.05) and stroke (p less than 0.01) in diabetic women and more than a twofold excess of coronary heart disease and cardiac failure in diabetic men (p less than 0.01). Femoral bruits doubled the risk of coronary heart disease in diabetic men (p less than 0.05). CONCLUSION We conclude that while diabetes predisposes to various forms and locations of peripheral arterial disease, the enhanced risk of acute cardiovascular events experienced by diabetic patients is increased further when diabetes is accompanied by indications of a peripheral arterial condition. Since signs of peripheral arterial disease may suggest an impending or coexistent atherosclerotic process, careful examination of arterial circulation by evaluating peripheral pulses and assessing whether bruits are present is important.

Family patterns of coronary heart disease mortality: the Framingham Longevity Study.

Family patterns for age at death were examined in a 40 year follow-up of 5209 men and women (2900 deceased, 2309 living) in the Framingham Study and their parents. Age at death of both mothers and fathers was significantly older for surviving offspring when compared to decreased offspring (p less than 0.0001). When longevity was assessed according to cause of death in the offspring, parental age at death was a significant predictor of death by coronary heart disease (CHD), but not for stroke or cancer. Multiple regression analysis for offspring with sudden CHD death revealed that mothers age at death was a significant predictor of age at sudden CHD death (p less than 0.0003) whereas fathers age at death was a significant predictor of age at death in non-sudden CHD death (p less than 0.004). Life table analysis showed longest survival rates associated with both parents surviving to age 75 or older followed by mother only surviving to age 75 or older, then father only, and shortest survival with neither parent surviving to age 75. Longevity appears to be more strongly associated with maternal death age than parental death age. Proportional hazards analysis of risk factors associated with CHD revealed that systolic blood pressure, sex of the individual, and cigarette smoking were the most significant predictors of death age. These findings suggest that familial similarities for death age may be mediated primarily through shared CHD risk factors within families, either genetic or non-genetic.

The Occurrence of Raynaud's Phenomenon in a General Population: The Framingham Study

The prevalence and predisposing conditions for primary and secondary Raynauds phenomenon (RP) were examined in The Framingham Study based on 16 years of follow-up of a cohort of 4182 men and women. The association with atypical chest pain and migraine headache was also investigated. Over the 16 years of follow-up there were 130 men and 171 women who developed primary RP. The prevalence in women (9.6%) was somewhat higher than in men (8.1%) and 81.4% of the RP was primary. Secondary RP was equally prevalent in men (18.6%) and women (19.7%). The most common causes of secondary RP were beta-blocker use (34.2%), carpal tunnel syndrome (10.5%) and rheumatoid arthritis (7.2%). Primary RP cases differed from noncases by having lower systolic blood pressure (p ≤ 0.001) and diastolic blood pressure (p < 0.0001), and more coronary disease (p = 0.009), smoking (p ≤ 0.01) and higher blood sugars (p ≤ 0.009). Atypical chest pain was present more often than noted previously in The Framingham Study general population survey, and was equally prevalent in primary and secondary RP and in the two sexes. Associated migraine was more prevalent in women (14.4%) than men (5.0%). Vibrating tool use with associated RP occurred in 14.6%.

Prevalence and correlates of posterior extra echocardiographic spaces in a free-living population based sample (the Framingham study)

To obtain epidemiologic information on extra echocardiographic spaces immediately posterior to the left ventricular free wall, 2,028 subjects in the original Framingham cohort study (mean age 70 +/- 7 years) and 3,624 of the offspring of the cohort (and their spouses) (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Extra echocardiographic spaces were detected in 370 (6.5%) of the 5,652 subjects. The prevalence ranged from less than 1% in subjects in the 20- to 30-year age decade to greater than 15% for those in their 80s. Extra echocardiographic spaces tended to be more common in subjects who were older, female, obese, more hypertensive, and who had higher blood sugar levels and higher low density lipoprotein cholesterol levels (measured 8 years earlier). The high prevalence of extra echocardiographic spaces and the independent association with age (cohort and offspring), obesity (cohort and male offspring), and ventricular septal hypertrophy (cohort and male offspring) is compatible with at least 2 hypotheses among others that should be tested: (1) Subepicardial fat may often masquerade as pericardial fluid producing a posterior extra echocardiographic space, especially in obese elderly subjects. (2) Small posterior extra echocardiographic spaces may often be early markers of subclinical hypertensive heart disease.

Glucose intolerance, physical signs of peripheral artery disease, and risk of cardiovascular events: the Framingham Study.

BACKGROUND Diabetes and peripheral artery disease (PAD) are acknowledged hallmarks of development of atherosclerotic cardiovascular disease (CVD). The prognostic implications of physical indicators of PAD, compared with and in conjunction with glucose intolerance based on population based data, are not well documented. METHODS AND RESULTS The influence of carotid and femoral bruits and nonpalpable pedal pulses, with and without glucose intolerance, on development of coronary disease (CHD), congestive heart failure (CHF), and stroke (CVA) was investigated in a cohort of 1672 men and 2264 women ages 47 to 99 years participating in the Framingham Study. Cross-sectional pooling yielded 29,063 2-year person-examination units based on the sample of whom 440 men and 484 women had glucose intolerance develop. Over the 26 years of follow-up, 210 men and 199 women had 1 or more of the specified CVD events. Logistic regression analysis was used to estimate age-adjusted odds ratios comparing incidence of CVD events in subjects with glucose intolerance, signs of PAD, or both conditions with those with neither condition. Glucose intolerance was associated with a 2-fold excess occurrence of physical signs of PAD (P< .01 ). Femoral and carotid bruits were generally associated with greater increased risk of CHD, CHF, and CVA than was glucose intolerance alone. Particularly in women, the concomitant presence of bruits augmented the CVD risk of glucose intolerance. Nonpalpable pedal pulses were a stronger risk factor for CVD end points than glucose intolerance; particularly in men and in both sexes, those with both conditions were at substantially greater risk of CVD events than those with either alone. CONCLUSIONS Physical findings of PAD appear to signify a compromised arterial circulation to the heart and brain as well as the limbs in persons with glucose intolerance. Persons with the combination are candidates at high risk for CHD, CHF, and CVA.

Epidemiologic assessment of angina before and after myocardial infarction: The Framingham Study

Angina pectoris before and after MI was evaluated in a sample of 729 men and women from a general population in whom MI developed during a 36-year period of follow-up. Relations of AP to subsequent CHD events and mortality after initial MI were analyzed by proportional hazards regression models and were adjusted for covariates (age, sex, blood pressure, serum cholesterol, body mass index, glucose intolerance, cigarette smoking, and antihypertensive medications) obtained from routine biennial examinations preceding the initial MI. Comparisons of the influence of angina were made between pre-MI angina, post-MI angina, and absence of AP. The sample had 484 men and 245 women (mean ages, 63 and 69, respectively) who survived greater than / equal to 30 days after MI. The initial MI was clinically unrecognized in 165 (34%) men and 115 (47%) women. Data on covariates were complete for 622 subjects, among whom 30% had pre-Ml angina, 18% had post-MI angina, and 52% did not have AP. Angina was half as common in persons with unrecognized MIs as in those with clinically recognized MIs. During an average of 8.7 years of follow-up, 57% of subjects developed subsequent CHD events, including recognized and unrecognized MI, coronary insufficiency, and CHD death, and 74% died. Both pre-MI angina (hazard ratio, 1.49; 95% CI, 1.17 to 1.91) and post-MI angina (hazard ratio, 1.43; 95% CI, 1.06 to 1.94) adjusted for accompanying risk factors were associated with increased risk for subsequent CHD events compared with those without AP. Neither pre-MI nor post-MI angina was associated with excess overall mortality.