Biomedical subjects

Michael J Pencina

Publications and source records attributed to Michael J Pencina.

14 recordsLinked to original sources

PubMed2007

Choice of time scale and its effect on significance of predictors in longitudinal studies.

Time-to-event regression is a frequent tool in biomedical research. In clinical trials this time is usually measured from the beginning of the study. The same approach is often adopted in the analysis of longitudinal observational studies. However, in recent years there has appeared literature making a case for the use of the date of birth as a starting point, and thus utilize age as the time-to-event. In this paper, we explore different types of age-scale models and compare them with time-on-study models in terms of the estimated regression coefficients they produce. We consider six proportional hazards regression models that differ in the choice of time scale and in the method of adjusting for the years before the study. By considering the estimating equations of these models as well as numerical simulations we conclude that correct adjustment for the age at entry is crucial in reducing bias of the estimated coefficients. The unadjusted age-scale model is inferior to any of the five other models considered, regardless of their choice of time scale. Additionally, if adjustment for age at entry is made, our analyses show very little to suggest that there exists any practically meaningful difference in the estimated regression coefficients depending on the choice of time scale. These findings are supported by four practical examples from the Framingham Heart Study.

Age Factors↗

PubMed2006

Estimating lifetime risk of developing high serum total cholesterol: adjustment for baseline prevalence and single-occasion measurements.

The lifetime risk statistic is a powerful tool in epidemiology. It has been successfully applied to estimate and highlight the risks of numerous diseases, including breast cancer, Alzheimer's disease, stroke, and coronary heart disease and some of its risk factors. Application of this method to health-related conditions that may have an onset early in young adulthood or to measurements that can fluctuate over time introduces problems of under- or overestimation of risk. To correctly quantify the long-term risk of developing high serum total cholesterol (> or =240 mg/dl or use of lipid-lowering medication), the authors propose a key modification of the lifetime risk statistic: adjustment for baseline prevalence. It accounts for the fact that many people already have the condition at a young age (an age often chosen as baseline). The authors derive point estimators and confidence intervals and supply a SAS macro (SAS Institute, Inc., Cary, North Carolina). For assessment of the risk inflation due to single-occasion measurement, the authors suggest two diagnostic tools, one requiring the condition to be present on two consecutive occasions and the other taking into account intrasubject variability. As an illustration, the authors calculate risk estimates for US Caucasians based on hypercholesterolemia incidence (1971-early 2001) from the Framingham Heart Study and prevalence data from the 1999-2000 National Health and Nutrition Examination Survey.

Adult↗

PubMed2006

Endogenous sex hormones and cardiovascular disease incidence in men.

BACKGROUND: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. OBJECTIVE: To examine the association of circulating sex hormone levels and CVD risk in men. DESIGN: Prospective cohort study. SETTING: Community-based study in Framingham, Massachusetts. PARTICIPANTS: 2084 middle-aged white men without CVD at baseline. MEASUREMENTS: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. RESULTS: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% CI, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age >56 years) men (hazard ratio per SD increment, 0.86 [CI, 0.78 to 0.96]; P = 0.005) but not in younger (median age < or =56 years) men (hazard ratio per SD increment, 1.11 [CI, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. LIMITATIONS: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. CONCLUSIONS: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men.

Cardiovascular Diseases↗

PubMed2006

Association of parental heart failure with risk of heart failure in offspring.

BACKGROUND: The association between heart failure in parents and the prevalence of left ventricular systolic dysfunction and the risk of heart failure in their offspring has not been investigated in a community-based setting. METHODS: We examined the cross-sectional association of heart failure in parents with the prevalence of left ventricular systolic dysfunction, as well as left ventricular mass, internal dimensions, and wall thickness, in 1497 participants of the Framingham Offspring Study (mean age, 57 years; 819 women) who underwent routine echocardiography. We also investigated prospectively whether heart failure in parents increased the risk of heart failure in 2214 offspring (mean age, 44 years; 1150 women). RESULTS: As compared with the 1039 participants whose parents did not have heart failure, the 458 participants in the cross-sectional cohort who had at least one parent with heart failure were more likely to have increased left ventricular mass (17.0 percent vs. 26.9 percent), left ventricular internal dimensions (18.6 percent vs. 23.4 percent), and left ventricular systolic dysfunction (3.1 percent vs. 5.7 percent); the multivariable-adjusted odds ratios were 1.35 (95 percent confidence interval, 0.99 to 1.84), 1.29 (95 percent confidence interval, 0.96 to 1.72), and 2.37 (95 percent confidence interval, 1.22 to 4.61), respectively. In the longitudinal cohort, heart failure developed in 90 offspring during follow-up (mean length of follow-up, 20 years). The age- and sex-adjusted 10-year incidence rates of heart failure were 2.72 percent among offspring with a parent with heart failure, as compared with 1.62 percent among those without a parent with heart failure. This increase in risk persisted after multivariable adjustment (hazard ratio, 1.70; 95 percent confidence interval, 1.11 to 2.60). CONCLUSIONS: Heart failure in parents is associated with an increased prevalence of left ventricular systolic dysfunction cross-sectionally and an elevated risk of heart failure longitudinally. Our data emphasize the contribution of familial factors to the heart-failure burden in the community.

Adult Children↗

PubMed2006

Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study.

BACKGROUND: Recent studies indicate that the prevalence of type 2 diabetes mellitus is increasing in the United States; less is known about trends in the incidence of type 2 diabetes mellitus. METHODS AND RESULTS: Participants free of diabetes mellitus (n=3104; mean age 47 years; 1587 women) from the Framingham Offspring Study who attended a routine examination in the 1970s, 1980s, or 1990s were followed up for the 8-year incidence of diabetes mellitus. Diabetes was defined as a fasting plasma glucose > or = 7.0 mmol/L or treatment with either insulin or a hypoglycemic agent. Pooled logistic regression was used to compare diabetes incidence across decades for participants between 40 and 55 years of age in each decade. The age-adjusted 8-year incidence rate of diabetes was 2.0%, 3.0%, and 3.7% among women and 2.7%, 3.6%, and 5.8% among men in the 1970s, 1980s, and 1990s, respectively. Compared with the 1970s, the age- and sex-adjusted odds ratio (OR) for diabetes was 1.40 (95% confidence interval [CI], 0.89 to 2.22) in the 1980s and 2.05 (95% CI, 1.33 to 3.14) in the 1990s (P for trend=0.0006). Among women, the OR was 1.50 (95% CI, 0.75 to 2.98) in the 1980s and 1.84 (95% CI, 0.95 to 3.55) in the 1990s (P for trend=0.07) compared with the 1970s, whereas among men, the OR was 1.33 (95% CI, 0.72 to 2.47) in the 1980s and 2.21 (95% CI, 1.25 to 3.90) in the 1990s (P for trend=0.003). Most of the increase in absolute incidence of diabetes occurred in individuals with body mass index > or = 30 kg/m2 (P for trend=0.03). CONCLUSIONS: In the present community-based sample of middle-aged adults, we observed a doubling in the incidence of type 2 diabetes over the last 30 years. Careful surveillance of changes in diabetes incidence may be necessary if current trends of excess adiposity continue.

Adult↗

PubMed2006

Electrocardiographic QRS duration and the risk of congestive heart failure: the Framingham Heart Study.

Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants (mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, <100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, > or =120 ms]. During follow-up (mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P<0.001]. In time- dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P=0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P<0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk.

Aged↗

PubMed2006

Nutritional risk and the metabolic syndrome in women: opportunities for preventive intervention from the Framingham Nutrition Study.

BACKGROUND: Diet is recognized as a key factor in the cause and management of the metabolic syndrome (MetS). However, policies to guide preventive clinical nutrition interventions of the condition are limited. OBJECTIVES: We examined the relation between dietary quality and incident MetS in adult women and identified foci for preventive nutrition interventions. DESIGN: This was a prospective study of 300 healthy women (aged 30-69 y) in the Framingham Offspring-Spouse study who were free of MetS risk factors at baseline. The development of individual MetS traits and overall MetS status during 12 y of follow-up were compared in women by tertile of nutritional risk, based on intake of 19 nutrients. Multivariate logistic regression models considered age, smoking, physical activity, and menopausal status. RESULTS: Baseline age-adjusted mean nutrient intake and ischemic heart disease risk profiles differed by tertile of nutritional risk. Women with higher nutritional risk profiles consumed more dietary lipids (total, saturated, and monounsaturated fats) and alcohol and less fiber and micronutrients; they had higher cigarette use and waist circumferences. Compared with women with the lowest nutritional risk, those in the highest tertile had a 2- to 3-fold risk of the development of abdominal obesity and overall MetS during 12 y of follow-up [odds ratio: 2.3 (95% CI: 1.2, 4.3) and 3.0 (95% CI: 1.2, 7.6), respectively]. CONCLUSIONS: Higher composite nutritional risk predicts the development of abdominal obesity and MetS during long-term follow-up in healthy women, independent of lifestyle and ischemic heart disease risk factors. Preventive nutrition interventions for obesity and MetS risk reduction should focus on the overall nutritional quality of women's dietary profiles.

Abdominal Fat↗

PubMed2005

Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults.

CONTEXT: While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear. OBJECTIVE: To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors. DESIGN, SETTING, AND PARTICIPANTS: The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least 1 sibling in the study; all were followed up for 8 years. MAIN OUTCOME MEASURES: Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence. RESULTS: Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% CI, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% CI, 1.32-3.00) exceeded that for parental CVD (1.45; 95% CI, 1.02-2.05). CONCLUSION: Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults.

Cardiovascular Diseases↗

PubMed2005

Estimated risks for developing obesity in the Framingham Heart Study.

BACKGROUND: The short- and long-term risks for developing overweight or obesity are unknown. OBJECTIVES: To estimate the short-term, long-term, and lifetime risks for developing overweight or obesity in adults in the community. DESIGN: Prospective cohort study, 1971 to 2001. SETTING: Community-based study, Framingham, Massachusetts. PARTICIPANTS: 4117 white participants (51.9% women) from the Framingham Heart Study. MEASUREMENTS: The short-term (4 years) and long-term (10 to 30 years) risks for ever becoming overweight or more (body mass index [BMI] > or = 25 kg/m2) or obese (BMI > or = 30 kg/m2) for men and women at 30, 40, and 50 years of age with a normal BMI (between 18.5 kg/m2 and 25.0 kg/m2). RESULTS: The observed 4-year rates of developing overweight varied from 14% to 19% in women and 26% to 30% in men. Four-year rates of developing obesity ranged from 5% to 7% in women and 7% to 9% in men. The long-term (30-year) risk estimates were similar for the 2 sexes generally; varied somewhat with age (in men, being lower for those 50 years of age); and, overall, exceeded 1 in 2 persons for overweight or more, 1 in 4 individuals for obesity, and 1 in 10 people for stage II obesity (BMI > or = 35 kg/m2) across different age groups. The 30-year estimates correspond to the residual lifetime risk for overweight or more or obesity for participants 50 years of age. LIMITATIONS: These findings may not be generalizable to other races or ethnicities. CONCLUSIONS: The long-term risks for overweight or more or obesity exceeded 50% and 25%, respectively, indicating a large public health burden. These estimates suggest that the future burden of obesity-associated diseases may be substantial.

Adult↗

PubMed2005

Relations of insulin sensitivity to longitudinal blood pressure tracking: variations with baseline age, body mass index, and blood pressure.

BACKGROUND: The relations of insulin sensitivity (IS) to hypertension incidence may vary according to baseline age, body mass index (BMI), and blood pressure (BP). METHODS AND RESULTS: We investigated the relations of IS (insulin sensitivity index, ISI(0,120)) to 4-year incidence of hypertension and BP progression in 1933 nonhypertensive Framingham Study participants (median age, 51 years; 56% women). Analyses were stratified by age (less than versus greater than or equal to median), BMI (<25 [normal], 25 to <30 [overweight], > or =30 kg/m2 [obese]), and BP category (systolic BP> or =130 or diastolic BP> or =85, "high normal" per the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP [JNC-VI] versus BP<130/85 mm Hg). On follow-up, 41% of participants had BP progression (> or =1 BP stage increase) and 18% had development of hypertension (systolic BP> or =140 or diastolic BP> or =90 mm Hg or antihypertensive medication use). In younger (<51 years) people with normal BMI and baseline BP<130/85 mm Hg, the second-to-fourth ISI(0,120) quartiles were associated with lower multivariable-adjusted odds for hypertension incidence (0.27; 95% CI, 0.09 to 0.83; P<0.05) and BP progression (0.37; 95% CI, 0.18 to 0.77; P<0.01) relative to the lowest (most insulin resistant) quartile. IS was not related to BP progression or hypertension incidence in older individuals, in obese participants, or in people with BP> or =130/85 mm Hg. CONCLUSIONS: In our large community-based sample, reduced IS predicted BP tracking principally in younger people with normal BMI and BP<130/85 mm Hg. Effect modification by age, BMI, and baseline BP may explain variation in the results of prior clinical investigations relating IS to hypertension incidence.

Adult↗

PubMed2005

Compliance with expert population-based dietary guidelines and lower odds of carotid atherosclerosis in women: the Framingham Nutrition Studies.

BACKGROUND: Carotid stenosis, an indicator of subclinical atherosclerosis, predicts future coronary artery disease (CAD) and stroke and provides a noninvasive method to identify candidates for primary prevention. The relation between diet and stenosis is relatively unexplored, particularly in women. OBJECTIVE: We evaluated in women the association between nutrient intakes that were consistent with expert population-based dietary guidelines and carotid stenosis. DESIGN: We used prospective logistic regression analyses to evaluate relations between baseline nutrient intake and the presence of carotid stenosis at 4-y follow-up in 1123 women from the Framingham Offspring-Spouse study, after control for multiple CAD risk factors. We also developed multivariate models that were stratified by compliance with expert population-based dietary guidelines and smoking status. RESULTS: Baseline nutrient and risk factor profiles differed by women's compliance and smoking status. Dietary noncompliance and smoking were each associated with odds for stenosis that were 2.5-fold those of dietary compliance and nonsmoking. Odds were highest for dietary noncompliance in combination with smoking (odds ratio: 3.49; 95% CI: 1.67, 7.27). CONCLUSIONS: Nutrient intake consistent with current expert population-based dietary guidelines and smoking abstinence are associated with lower odds of carotid atherosclerosis in women. Unique dietary and risk factor profiles of at-risk women suggest areas for targeted primary CAD prevention.

Adult↗

PubMed2005

Cardiovascular risk factors predictive for survival and morbidity-free survival in the oldest-old Framingham Heart Study participants.

OBJECTIVES: To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85. DESIGN: Prospective community-based cohort study. SETTING: Framingham Heart Study, Massachusetts. PARTICIPANTS: Two thousand five hundred thirty-one individuals (1,422 women) who attended at least two examinations between the ages of 40 and 50. MEASUREMENTS: Risk factors were classified at routine examinations performed between the ages of 40 and 50. Stepwise sex-adjusted logistic regression models predicting the outcomes of survival and survival free of morbidity to age 85 were selected from the following risk factors: systolic and diastolic blood pressure, total serum cholesterol, glucose intolerance, cigarette smoking, education, body mass index, physical activity index, pulse pressure, antihypertensive medication, and electrocardiographic left ventricular hypertrophy. RESULTS: More than one-third of the study sample survived to age 85, and 22% of the original study sample survived free of morbidity. Lower midlife blood pressure and total cholesterol levels, absence of glucose intolerance, nonsmoking status, higher educational attainment, and female sex predicted overall and morbidity-free survival. The predicted probability of survival to age 85 fell in the presence of accumulating risk factors: 37% for men with no risk factors to 2% with all five risk factors and 65% for women with no risk factors to 14% with all five risk factors. CONCLUSION: Lower levels of key cardiovascular risk factors in middle age predicted overall survival and major morbidity-free survival to age 85. Recognizing and modifying these factors may delay, if not prevent, age-related morbidity and mortality.

Academic Medical Centers↗

PubMed2004

Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation.

The assessment of the discrimination ability of a survival analysis model is a problem of considerable theoretical interest and important practical applications. This issue is, however, more complex than evaluating the performance of a linear or logistic regression. Several different measures have been proposed in the biostatistical literature. In this paper we investigate the properties of the overall C index introduced by Harrell as a natural extension of the ROC curve area to survival analysis. We develop the overall C index as a parameter describing the performance of a given model applied to the population under consideration and discuss the statistic used as its sample estimate. We discover a relationship between the overall C and the modified Kendall's tau and construct a confidence interval for our measure based on the asymptotic normality of its estimate. Then we investigate via simulations the length and coverage probability of this interval. Finally, we present a real life example evaluating the performance of a Framingham Heart Study model.

Cohort Studies↗

PubMed2004

Cross-sectional relations of urinary sodium excretion to cardiac structure and hypertrophy. The Framingham Heart Study.

BACKGROUND: Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP, in the community. METHODS: We analyzed the cross-sectional relationships between urinary sodium excretion and LV measurements in a community-based sample of 2660 Framingham Offspring Study participants (mean age 58 years, 56% women and 44% men). Participants with known coronary artery disease, congestive heart failure, or renal failure as well as those using diuretics were excluded. Urinary sodium excretion was measured on a spot urine sample and was indexed to urinary creatinine. RESULTS: In sex-specific, multivariable linear regression models adjusting for covariates known to influence LV measurements, log urinary sodium was not associated with LV mass, wall thickness, end-diastolic dimensions, or left atrial size in either sex. Urinary sodium was not related to LVH defined as LV mass >/= sex-specific 80th percentile value. In analyses restricted to hypertensive individuals (n = 983, 470 women), urinary sodium was not associated with LV mass or LVH. CONCLUSIONS: In our large community-based sample, urinary sodium excretion was not related to LV mass, function, or hypertrophy.

Aged↗