Biomedical subjects

M G Larson

Publications and source records attributed to M G Larson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Differential control of systolic and diastolic blood pressure : factors associated with lack of blood pressure control in the community.

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.

Aged↗

PubMed1999

Temporal trends in event rates after Q-wave myocardial infarction: the Framingham Heart Study.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed1999

Cross-classification of JNC VI blood pressure stages and risk groups in the Framingham Heart Study.

BACKGROUND: 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). OBJECTIVE: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed1999

Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study.

BACKGROUND: Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. METHODS AND RESULTS: We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest chi(2) statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0. 86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (<120, 120 to 139, 140 to 159, and >/=160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results. CONCLUSIONS: In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP>/=120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.

Aged↗

PubMed1999

Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.

BACKGROUND: Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain. OBJECTIVE: To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes. DESIGN: Community-based, prospective observational study. SETTING: Framingham, Massachusetts. PATIENTS: 6763 Framingham Heart Study participants (mean age, 47 years). MEASUREMENTS: Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile. RESULTS: During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes. CONCLUSIONS: These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.

Age Distribution↗

PubMed1999

Prevalence and clinical outcome of mitral-valve prolapse.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed1999

Heritability of heart rate variability: the Framingham Heart Study.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed1999

Blood pressure response during treadmill testing as a risk factor for new-onset hypertension. The Framingham heart study.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMed1999

Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study)

Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9 years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m2; 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs.

Adult↗

PubMed1999

Lifetime risk of developing coronary heart disease.

BACKGROUND: The lifetime risk of developing coronary heart disease has not been estimated in a general population. We investigated the lifetime risks of initial coronary events at different ages. METHODS: We assessed data for 7733 participants in the Framingham Heart Study, who had been examined at least once at age 40-94 years between 1971 and 1975, found to be free of coronary heart disease, and then followed up. We estimated the lifetime risks of coronary heart disease (angina pectoris, coronary insufficiency, myocardial infarction, or death from coronary heart disease) by multiple-decrement life-table methods. FINDINGS: The 7733 patients were followed up for a total of 109,948 person-years. Overall, 1157 participants developed coronary heart disease. 1312 died from non-coronary heart disease causes. Lifetime risk of coronary heart disease at age 40 years was 48.6% (95% CI 45.8-51.3) for men and 31.7% (29.2-34.2) for women. At age 70 years, lifetime risk was 34.9% (31.2-38.7) for men and 24.2% (21.4-27.0) for women. After we excluded isolated angina pectoris as an initial event, the lifetime risk of coronary artery disease events at age 40 years was 42.4% for men and 24.9% for women. INTERPRETATION: Lifetime risk at age 40 years is one in two for men and one in three for women. Even at age 70 years it is one in three for men and one in four for women. This knowledge may promote efforts in education, screening, and treatment for prevention of coronary heart disease in younger and older patients.

Adult↗

PubMed1999

Association of left ventricular dilatation and hypertrophy with chronotropic incompetence in the Framingham Heart Study.

BACKGROUND: Chronotropic incompetence and left ventricular (LV) dilatation have both been shown to be markers of an adverse cardiovascular prognosis. Chronotropic incompetence has been described in patients with symptomatic LV dilatation and dysfunction, but the effect of asymptomatic LV dilatation and hypertrophy on exercise heart rate response has not been well characterized. METHODS AND RESULTS: Members of the Framingham Offspring Study underwent M-mode echocardiography and graded exercise testing as part of a routine evaluation. Subjects receiving beta-blockers and digitalis and subjects with preexisting coronary heart disease, heart failure, and baseline ST-segment abnormalities were excluded. Chronotropic incompetence was assessed in 2 ways: (1) failure to achieve an age--predicted target heart rate and (2) a low chronotropic index, a measure of heart rate response that takes into account effects of age, resting heart rate, and physical fitness. Echocardiographic variables studied included LV diastolic and systolic dimensions, LV wall thickness, LV mass, and fractional shortening. There were 1414 men and 1601 women eligible for analyses; failure to reach target heart rate occurred in 20% of men and 23% of women; a low chronotropic index was noted in 14% of men and 12% of women. In unadjusted categorical analyses, an abnormally high LV mass, as defined by exceeding the 90th percentile predicted value of a healthy reference group, was associated with failure to achieve target heart rate in men (31% vs 18%, odds ratio [OR] 2.05, 95% confidence interval [CI] 1.49 to 2.83) and women (34% vs 20%, OR 2.09, 95% CI 1.63 to 2.69). Similarly, an abnormally high LV mass was predictive of a low chronotropic index in men (18% vs 13%, OR 1. 47, 95% CI 1.01 to 2.14) and women (17% vs 10%, OR 1.78, 95% CI 1.29 to 2.45). When considered as a continuous variable, LV diastolic dimension predicted failure to achieve target heart rate in men (ageadjusted OR for 1 SD increase 1.30, 95% CI 1.00 to 1.33) and in women (age-adjusted OR 1.30, 95% CI 1.12 to 1.50). Similarly, LV diastolic dimension predicted low chronotropic index in men (age-adjusted OR 1.22, 95% CI 1.05 to 1.42) and in women (age-adjusted OR 1.18, 95% CI 1.01 to 1.39). After also adjusting for resting blood pressure, physical activity, and other potential confounders, LV mass, when considered as a continuous variable, remained predictive of failure to achieve target heart rate in men (adjusted OR 1.23, 95% CI 1.06 to 1.42) and a low chronotropic index in men (adjusted OR 1.26, 95% CI 1.06 to 1.49). Among women, LV diastolic dimension predicted failure to achieve target heart rate (adjusted OR 1.27, 95% CI 1.12 to 1.45) and low chronotropic index (adjusted OR 1.18, 95% CI 1.01 to 1.39), whereas in men it predicted low chronotropic index (adjusted OR 1.22, 95% CI 1.04 to 1.42). CONCLUSIONS: In this asymptomatic, population-based cohort, chronotropic incompetence was predicted by increased LV mass and cavity size; among men, it was also predicted by depressed systolic function.

Adult↗

PubMed1999

The association of chronic cough with the risk of myocardial infarction: the Framingham Heart Study.

PURPOSE: A persistent inflammatory response accompanying chronic infections may contribute to the risk of coronary atherothrombosis. Recent studies have reported an association between chronic respiratory infections and an increased risk of coronary heart disease; however, these reports have not accounted for important confounders such as impaired lung function. METHODS: We considered chronic cough as an indicator of chronic lung infection or inflammation in the original Framingham Heart Study participants aged 47 to 89 years. Chronic cough was defined as a cough present for at least 3 months in the preceding year and was categorized as either nonproductive or productive. The association of chronic cough with myocardial infarction was examined for six consecutive examination cycles (1965 to 1979) among participants free of myocardial infarction at the baseline examination. In a secondary analysis, plasma fibrinogen levels were measured during examination cycle 10 (1965 to 1967) in a subgroup of the study sample (n = 1,288). Multivariable logistic regression analysis was performed adjusting for age, gender, smoking status, forced vital capacity, and other known risk factors. RESULTS: The cross-sectional pooling method yielded 15,656 person-examinations in 3,637 subjects. During follow-up, there were 291 incident myocardial infarctions. Chronic nonproductive cough (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1 to 2.8) and chronic productive cough (OR 1.6, CI 1.1 to 2.4) were independent predictors of myocardial infarction. Results were unchanged when we further adjusted for a history of heart failure. Adjusted plasma fibrinogen levels (mean +/- SD) were greater in those with chronic nonproductive cough than among those without cough (3.2 +/- 0.6 g/L versus 2.9 +/- 0.6 g/dL, P = 0.001). CONCLUSIONS: These findings provide evidence that chronic cough, a clinical manifestation of pulmonary infection or chronic inflammation, is associated with the risk of myocardial infarction. Acute phase reactants such as plasma fibrinogen may be implicated in this association. Prospective serologic studies of infections as predictors of coronary heart disease risk are warranted.

Aged↗

PubMed1999

Discrepancies between self-reported and observed physical function in the elderly: the influence of response shift and other factors.

GOAL: To explore the influence of social, psychological, and health factors on self-report of function. SUBJECTS: A convenience sample of 289 community-dwelling elderly aged 65-97 years. METHODS: We compared a measure of function based on observed performance, the Physical Capacity Evaluation (PCE) with a self-reported measure of functional limitations (HAQ), in a cross-sectional study. Stepwise multiple regression identified variables predicting self-reported disability, controlling for observed function. RESULTS: Controlling for PCE, self-reports of greater disability (HAQ) were predicted by current joint pain or stiffness, use of prescription medications, urban dwelling, depression, female gender, lack of memory problems, arthritis and lack of exercise. A final model included recent decline in function, dissatisfaction with function, gender, joint pain or stiffness, and observed function, explaining 85% of the variance in self-reported disability. The hypothesis that aging is associated with declining expectations of functional ability was not supported. However, recent health problems affected participants' reporting of limitations, consistent with a recalibration-type response shift. Perceived decline in function over the past six months, a fall within the last month, illness in the last week and pain or stiffness on the day of the exam all raised self-reports of disability. As suggested by adaptation level theory, subjects with recent problems might have an inflated perception of limitations due to shifts in their internal standards. When administered first, the observed performance test improved correlations between observed and self-reported function, primarily among those who did not report a recent decline in function. This suggests that this group may have benefited more from salient information about their abilities provided by performing the PCE before self-report. CONCLUSION: Our data confirm the importance of social, psychological, and health influences in self-report of disability, and are consistent with the hypothesis that people may recalibrate their self assessments based on recent health problems.

Aged↗

PubMed1999

Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adult↗

PubMed1999

A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study.

Genetic variation at the lipoprotein lipase (LPL) locus has been shown to influence plasma lipids and to modulate risk of coronary heart disease (CHD). Recently, we found that the most frequent variant at this locus, involving a C-terminal truncation of two amino acids (Ser447X), was associated with both higher LPL activity and high density lipoprotein cholesterol (HDL-C) in patients with CHD. However, the impact of this S447X variant on lipids and CHD in the general population was hitherto unknown. We, therefore, analyzed a total of 1114 men and 1144 women randomly ascertained from the Framingham Offspring Study (FOS) for the presence of this LPL variant. Carrier frequency of the S447X allele was 17%, and in men carrier status was associated with higher total cholesterol (delta = 6.2 mg/dl, p = 0.03). higher HDL-C (delta = 2.3 mg/dl, p = 0.01), and lower triglyceride (TG) levels (delta = -19.4 mg/dl, p = 0.02). Moreover, in men, the S447X allele conferred significant protection against CHD (odds ratio: 0.43; p = 0.04). These effects on lipids and CHD were not seen in women. Our study represents the first report on the impact of this mutation on CHD in men from the general population, and we conclude, therefore, that the S447X variant may confer significant protection against high TG levels, low HDL-C, and premature CHD in these subjects.

Adult↗

PubMed1999

Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women.

We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (delta = - 0.07 mmol/ 1, p = 0.03) and a trend towards increased triglycerides (delta = 0.25 mmol/ 1, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (delta = - 0.02 mmol/1 for HDL-C and delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels for D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women.

Cholesterol, HDL↗

PubMed1999

Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency.

UNLABELLED: Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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PubMed1999

Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.

The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were 0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L (0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the PlA2 allotype with increased risk for cardiovascular disease.

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