The fact and fiction of lowering cholesterol concentrations in the primary prevention of coronary heart disease.
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Anticholesteremic Agents↗
Biomedical subjects
W P Castelli
Publications and source records attributed to W P Castelli.
Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.
BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS: We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS: We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.
Age Factors↗
Epidemiology of triglycerides: a view from Framingham.
New analyses from the Framingham Heart Study are presented showing that men and women who have high triglyceride levels (> 1.7 mmol/liter) and a low high-density lipoprotein (HDL) level (< 1.03 mmol/liter) run a significantly higher rate of coronary artery disease and can be identified, and that this risk group (high triglyceride-low HDL) is, independently of the major risk factors (including low HDL), related to occurrence of coronary artery disease. Further, this trait appears to be common in our society, producing twice as many cases of coronary artery disease during the 14 years of the Framingham study as the next highest disease-producing lipid abnormality. This trait of high triglyceride-low HDL is associated in the medical literature with increased insulin resistance, higher blood sugars (within the normal range), higher uric acid levels, hypertension, and centrally mediated obesity. Because total cholesterol in people with these traits may be less than or just slightly greater than 5.2 mmol/liter, they are missed or neglected by most cholesterol screening programs.
Adult↗
Myocardial infarction and coronary death among women: psychosocial predictors from a 20-year follow-up of women in the Framingham Study.
This study investigates the relation of psychosocial variables to the 20-year incidence of myocardial infarction or coronary death among women in the Framingham Study. In 1965-1967, a psychosocial interview was given along with the collection of other coronary risk factor data. This study includes 749 women aged 45-64 years who were free of coronary disease at this baseline examination. Demographic variables, psychosocial scales (such as tension and reactions of anger), and individual interview items (such as attitudes toward children, money, and religion) were measured. When age, systolic blood pressure, the ratio of serum total cholesterol to high-density lipoprotein cholesterol, diabetes, cigarette smoking, and body mass index were controlled for in multivariate proportional hazards models, the predictors of the 20-year incidence of myocardial infarction or coronary death were as follows: among employed women, perceived financial status only; among homemakers, symptoms of tension and anxiety, being lonely during the day, difficulty falling asleep, infrequent vacations, housework affecting health, and believing one is prone to heart disease (p less than 0.05 for all variables); and among both groups of women combined, low educational level, tension, and lack of vacations. These results are discussed in relation to previous findings from the Framingham Study.
Analysis of Variance↗
LDL particle size distribution. Results from the Framingham Offspring Study.
Using 2-16% gradient gel electrophoresis, we examined low density lipoprotein (LDL) particle size in relation to plasma lipoproteins in 1,168 women and 1,172 men from the Framingham Offspring Study. In addition, we studied the effect of dietary intake on LDL size in a subset of the population. Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019-1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL5 in d = 1.038-1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml. Seventy-seven percent of the population had one major and at least one minor LDL peak. Secondary LDL peaks accounted for 23% of the total LDL relative area, based on laser scanning densitometry. LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL 1, 30% and of LDL 2, 31%), whereas men exhibited a more symmetric distribution (prevalence of LDL 3, 42%). The prevalence of small (< 255 A), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-I levels. In addition, we found a significant (p < 0.0001) association between LDL cholesterol and LDL size. The highest LDL cholesterol levels were found among women with LDL 4 (148 mg/dl) and men with LDL 3-5 (138 mg/dl). In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels. We also found that compared with subjects with optimal LDL cholesterol levels (< 130 mg/dl), individuals with high-risk LDL cholesterol levels (> or = 160 mg/dl) had 1) a higher prevalence of LDL 3 and 4 (women only) and a lower prevalence of LDL 1 and 2 (women only) and 2) 11% higher LDL cholesterol to apo B ratios, even when matched for LDL particle size. Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles. Therefore, the identification of small, dense LDL particles per se may not be a good indicator of coronary artery disease risk in population studies.(ABSTRACT TRUNCATED AT 400 WORDS)
Apolipoproteins↗
Echocardiographic left ventricular hypertrophy: clinical characteristics. The Framingham Heart Study.
Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted.
Adolescent↗
Concerning the possibility of a nut...
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Cholesterol↗
Relation of alcohol intake to left ventricular mass: The Framingham Study.
Alcohol has direct toxic effects on the myocardium and is associated with elevated blood pressure, but its relation to left ventricular mass independent of blood pressure level has not been assessed. Reported alcohol intake and left ventricular mass measured by echocardiography were evaluated in 1,980 men and 2,511 women 17 to 90 years of age and free of cardiovascular disease in the Framingham offspring and cohort study. The relation of reported alcohol intake to left ventricular mass was assessed by gender-specific multivariate regression analysis adjusting for age, height, body mass index, systolic blood pressure, history of hypertension and cigarette smoking. Alcohol intake was positively associated with left ventricular mass in men (p less than 0.01) but not in women (p = 0.64). When stratified by beverage type, beer and wine in both men and women and liquor in men were positively related to left ventricular mass. The lack of association of total alcohol intake to left ventricular mass in women appeared to be due to a negative association (p less than 0.01) with liquor. The strongest positive associations were with wine in men (p less than 0.001) and beer in women (p less than 0.05). Alcohol use is independently associated with left ventricular mass; this association may vary by beverage type. In persons with unexplained left ventricular hypertrophy, excessive alcohol intake should be considered.
Adolescent↗
Twelve-year incidence of coronary heart disease in middle-aged adults during the era of hypertensive therapy: the Framingham offspring study.
PURPOSE: To provide information on the incidence of coronary heart disease (CHD) in the offspring of the original cohort from the Framingham Heart Study. PATIENTS AND METHODS: From 1972 to 1974, offspring of the original participants in the Framingham Heart Study underwent a baseline examination for standard cardiovascular risk factors. At entry into the study, these offspring were 30 to 59 years old and free of CHD. They were followed for 12 years, during which time 156 of 1,663 men and 55 of 1,714 women developed CHD. RESULTS: In a multivariate proportional hazards model, CHD was significantly associated with age, lower high-density lipoprotein cholesterol (HDL-C) levels, and number of cigarettes smoked. Fasting glucose levels and low-density lipoprotein cholesterol (LDL-C) were highly associated with CHD in men, but borderline in women, while triglycerides and very-low-density lipoprotein cholesterol were not significantly associated with CHD after adjustment for HDL-C and glucose. Blood pressure medication was used in half of the hypertensive individuals, and systolic pressure was associated with CHD in women only. CONCLUSIONS: This study confirms the importance of the common CHD risk factors of cigarette smoking and LDL-C, and extends the prognostic role of HDL-C in a middle-aged cohort. The impact of blood pressure, with or without use of hypertensive medications, was reduced in this study, and the data suggest that this attenuation was due to successful treatment.
Adult↗
The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).
Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.
Aged↗
Triglycerides and serum cholesterol.
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Cholesterol↗
Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.
A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subject's height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.
Blood Pressure↗
Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity (the Framingham Study).
Left ventricular (LV) hypertrophy has been found to predispose to increased cardiovascular morbidity and mortality. To assess the clinical correlates and potential determinants of LV mass, the relation of echocardiographically determined LV mass to a variety of clinical parameters was examined in a general population. From 1979 to 1983 Framingham Heart Study participants underwent routine evaluation including medical history, physical examination and M-mode echocardiography. LV mass was determined using an anatomically validated formula that incorporates measurements of LV wall thickness and LV internal diameter. The study population consisted of 2,226 men and 2,746 women (mean age 51 years, range 17 to 90). Age, height, systolic blood pressure and body mass index (a measure of obesity) were statistically significant and independent correlates of LV mass in both sexes (p less than 0.001). In men under age 50, leisure-time physical activity was associated with LV mass (p less than 0.05), but this was not observed in women. Results from multivariate analyses in which body mass index and subscapular skinfold thickness were included suggest that lean body mass is correlated with LV mass. Maintenance of ideal body weight and normal blood pressure, weight reduction in obese persons and blood pressure control in hypertensive patients may contribute to the primary and secondary prevention of LV hypertrophy and its sequelae. Clinical interpretation of echocardiograms should include consideration of the correlates of LV mass to gain better insight into the pathogenesis of LV hypertrophy.
Age Factors↗
Stratifying the patient at risk from coronary disease: new insights from the Framingham Heart Study.
Although cardiovascular disease remains the leading cause of death in the United States, cardiovascular disease mortality has decreased steadily during the past 2 decades. This trend is largely attributable to improved detection and management of cardiovascular risk factors, in which the Framingham Heart Study has played a major role. This article examines some of the risk factors associated with coronary heart disease, notably, advancing age, hypertension, left ventricular hypertrophy, smoking, elevated serum cholesterol, and reduced high-density lipoprotein, all of which have been investigated by the Framingham Heart Study. In addition, new data are presented from a multidimensional model of coronary heart disease. This is a novel approach that takes into account the interactions of multiple risk factors and their contribution to overall coronary heart disease risk.
Adult↗
Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy.
Numerous electrocardiographic criteria, which are largely dependent on fixed voltage thresholds, have been proposed for the diagnosis of left ventricular hypertrophy (LVH). Electrocardiographic criteria for LVH were examined in 4,684 subjects of the Framingham Heart Study who underwent echocardiographic study for LVH. Echocardiographic LVH was detected in 290 men (14.2%) and 465 women (17.6%). Electrocardiographic features of LVH were present in 2.9% of men (60/2,042) and 1.5% of women (39/2,642). The overall sensitivity of the electrocardiographic diagnosis of LVH was 6.9%, whereas specificity was 98.8%. Sensitivity of the electrocardiogram (ECG) for LVH was marginally lower in women than in men (5.6% vs. 9.0%, p = 0.075). Obesity was inversely associated with sensitivity (p less than 0.05, both sexes combined, sex-adjusted). Smoking was also inversely related to sensitivity (p = 0.001, both sexes combined, sex-adjusted). In contrast, sensitivity of the ECG increased with age (p less than 0.001, both sexes combined, sex-adjusted). These findings suggest that electrocardiographic detection of LVH can be improved by incorporating information about noncardiac factors that impact on electrocardiographic sensitivity for LVH, presumably by attenuating QRS voltage. New strategies that take into consideration sex, age, smoking status, and obesity might improve the sensitivity of the ECG without diminishing specificity.
Age Factors↗
The role of plasma lipids as predictors of risk for coronary heart disease.
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Cholesterol↗
Diet, smoking, and alcohol: influence on coronary heart disease risk.
The Framingham study on coronary heart disease (CHD) has shown that life-style, particularly diet, smoking, and alcohol consumption, has a great impact on the incidence of CHD. Blood lipoproteins, rather than total blood cholesterol, have been found to be more accurate predictors of CHD risk. Blood triglyceride, previously considered to have little bearing on CHD risk, was found to have a negative impact in many cases. A population subgroup with high triglyceride greater than or equal to 1.7 mmol/L (greater than or equal to 150 mg/dL), low high-density lipoprotein less than or equal to 1.04 mmol/L (less than or equal to 40 mg/dL), increased insulin resistance, and a higher incidence of diabetes mellitus has been found to be at increased risk for CHD. Diet intervention trials have shown that a reduction in total cholesterol and saturated fat consumption produced reduction in CHD incidence proportionate to the fall in cholesterol. Cigarette smoking increased CHD risk moderately; those who smoked one pack per day had twice the risk of nonsmokers. Alcohol consumption actually lowered CHD incidence in the Framingham study; however, when alcohol consumption was greater than two drinks per day, a rise in mortality from cancer and stroke was observed.
Coronary Disease↗
Cardiovascular risk factors in the elderly.
The relation of total plasma cholesterol to the incidence of coronary heart disease (CHD) was one of the first findings of the Framingham Heart Study. The Framingham data established that a 1% increase in total cholesterol produced a 2% increase in CHD incidence. This relation has now been shown to apply to persons aged 60 to 70 years as well as to younger persons. The risk of CHD associated with various factors, including total cholesterol, low- and high-density lipoprotein and triglyceride levels, uric acid, blood glucose level, fibrinogen level and hypertensive blood pressure, is discussed with particular reference to the elderly. New data from the Framingham group show that increased left ventricular mass may be a significant risk factor for CHD, particularly among the elderly.
Adult↗