Association of 10-year and lifetime predicted cardiovascular disease risk with subclinical atherosclerosis in South Asians: findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study.

BACKGROUND: Ten-year and lifetime cardiovascular risk assessment algorithms have been adopted into atherosclerotic cardiovascular disease (ASCVD) prevention guidelines, but these prediction models are not based on South Asian populations and may underestimate the risk in Indians, Pakistanis, Bangladeshis, Nepali, and Sri Lankans in the United States. Little is known about ASCVD risk prediction and intermediate endpoints such as subclinical atherosclerosis in US individuals of South Asian ancestry. METHODS AND RESULTS: South Asians (n=893) from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study who were 40 to 79 years and free of ASCVD were included. Ten-year ASCVD predicted risk was calculated using the 2013 Pooled Cohort Equations. Lifetime predicted risk was based on risk factor burden. Baseline levels of subclinical atherosclerosis (coronary artery calcium [CAC] and carotid intima media thickness [CIMT]) were compared across 10-year and lifetime risk strata: (1) high (≥7.5%) 10-year and low (<7.5%) 10-year risk; (2) high (≥39%) lifetime and low (<39%) lifetime risk. South Asian men and women with high 10-year predicted risk had a significantly greater CAC burden than those with low 10-year risk. South Asians with high lifetime predicted risk had a significantly increased odds for CAC higher than 0 (odds ratio: men 1.97; 95% CI, 1.2 to 3.2; women 3.14; 95% CI, 1.5, 6.6). Associations between risk strata and CIMT were also present. CONCLUSION: This study is the first to provide evidence that contemporary ASCVD risk assessment algorithms derived from non-Hispanic white and African-American samples can successfully identify substantial differences in atherosclerotic burden in US South Asians.

Risk factor and prediction modeling for sudden cardiac death in women with coronary artery disease.

BACKGROUND: To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD. METHODS: The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed. RESULTS: Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001). CONCLUSIONS: Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.

Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study.

BACKGROUND: Dyslipidemia causes coronary heart disease in middle-aged and elderly adults, but the consequences of lipid exposure during young adulthood are unclear. OBJECTIVE: To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age. DESIGN: Prospective cohort study. SETTING: 4 cities in the United States. PARTICIPANTS: 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in Young Adults) study. MEASUREMENTS: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study; these measurements were then related to coronary calcium scores assessed later in life (45 years [SD, 4]). RESULTS: 2824 participants (87%) had nonoptimal levels of LDL cholesterol (>or=2.59 mmol/L [>or=100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60 mg/dL]), or triglycerides (>or=1.70 mmol/L [>or=150 mg/dL]) during young adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001). The association was similar across race and sex and strongly graded, with odds ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of 3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of 4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other coronary risk factors. Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinically abnormal lipid levels were excluded. LIMITATION: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome. CONCLUSION: Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Racial differences in atrial fibrillation prevalence and left atrial size.

BACKGROUND: Previous studies relying on clinical care data have suggested that atrial fibrillation is less common in African Americans than Caucasians, but the mechanism remains unknown. Clinical care may itself vary by race, potentially affecting the accuracy of atrial fibrillation ascertainment in studies relying on clinical data. We sought to examine racial differences in atrial fibrillation prevalence determined by protocol-driven electrocardiograms (ECGs) obtained in prospective cohort studies and to study racial differences in echocardiographic characteristics. METHODS: We pooled primary data from 3 cohort studies with atrial fibrillation adjudicated from study protocol ECGs and documentation of potentially important confounders: the Heart and Soul Study (n=1014), the Heart and Estrogen-Progestin Replacement Study (n=2673), and The Osteoporotic Fractures in Men Sleep Study (n=2911). Left atrial anatomic dimensions were compared among races from sinus rhythm echocardiograms in the Heart and Soul Study. RESULTS: Of the 6611 participants, 268 (4%) had atrial fibrillation: Caucasians had the highest prevalence (5%), and African Americans had the lowest (1%; P<.001 for each compared with all other races). After adjustment for potential confounders, Caucasians had a 3.8-fold greater odds of having atrial fibrillation than African Americans (95% confidence interval, 1.6-8.8, P=.002). Although ventricular and atrial volumes and function were similar in Caucasians and African Americans, Caucasians had a 2 mm larger anterior-posterior left atrial diameter after adjusting for potential confounders (95% confidence interval, 1-3 mm, P<.001). CONCLUSION: ECG confirmed atrial fibrillation is more common in Caucasians than in African Americans, which might be related to the larger left atrial diameter observed in Caucasians.

Cross-sectional and longitudinal associations between objectively measured sleep duration and body mass index: the CARDIA Sleep Study.

Numerous studies have found an association between shorter sleep duration and higher body mass index (BMI) in adults. Most previous studies have been cross-sectional and relied on self-reported sleep duration, which may not be very accurate. In the Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study (2000-2006), the authors examine whether objectively measured sleep is associated with BMI and change in BMI. They use several nights of wrist actigraphy to measure sleep among participants in an ongoing cohort of middle-aged adults. By use of linear regression, the authors examine whether average sleep duration or fragmentation is associated with BMI and 5-year change in BMI, adjusting for confounders. Among 612 participants, sleep duration averaged 6.1 hours and was grouped into 4 categories. Both shorter sleep and greater fragmentation were strongly associated with higher BMI in unadjusted cross-sectional analysis. After adjustment, BMI decreased by 0.78 kg/m(2) (95% confidence interval: -1.6, -0.002) for each increasing sleep category. The association was very strong in persons who reported snoring and weak in those who did not. There were no longitudinal associations between sleep measurements and change in BMI. The authors confirmed a cross-sectional association between sleep duration and BMI using objective sleep measures, but they did not find that sleep predicted change in BMI. The mechanism underlying the cross-sectional association is not clear.

Association between sleep and blood pressure in midlife: the CARDIA sleep study.

BACKGROUND: Epidemiological studies have reported an association between self-reported short sleep duration and high blood pressure (BP). Our objective was to examine both cross-sectional and longitudinal associations between objectively measured sleep and BP. METHODS: This study is ancillary to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. Blood pressure was measured in 2000 and 2001 and in 2005 and 2006. Sleep was measured twice using wrist actigraphy for 3 consecutive days between 2003 and 2005. Sleep duration and sleep maintenance (a component of sleep quality) were calculated. Analyses included 578 African Americans and whites aged 33 to 45 years at baseline. Outcome measures were systolic BP (SBP) and diastolic BP (DBP) levels, 5-year change in BP, and incident hypertension. RESULTS: After we excluded the patients who were taking antihypertensive medications and adjusted for age, race, and sex, shorter sleep duration and lower sleep maintenance predicted significantly higher SBP and DBP levels cross-sectionally as well as more adverse changes in SBP and DBP levels over 5 years (all P < .05). Short sleep duration also predicted significantly increased odds of incident hypertension (odds ratio, 1.37; 95% confidence interval, 1.05-1.78). Adjustment for 16 additional covariates, including snoring and daytime sleepiness, slightly attenuated the associations between sleep and BP. Sleep duration appeared to mediate the difference between African Americans and whites in DBP change over time (P = .02). CONCLUSION: Reduced sleep duration and consolidation predicted higher BP levels and adverse changes in BP, suggesting the need for studies to investigate whether interventions to optimize sleep may reduce BP.

Racial differences in incident heart failure among young adults.

BACKGROUND: The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS: We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS: Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS: Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

Prehypertension during young adulthood and coronary calcium later in life.

BACKGROUND: High blood pressure in middle age is a well-established risk factor for cardiovascular disease, but the consequences of low-level elevations during young adulthood are unknown. OBJECTIVE: To measure the association between prehypertension exposure before age 35 years and coronary calcium later in life. DESIGN: Prospective cohort study. SETTING: Four communities in the United States. PARTICIPANTS: Black and white men and women age 18 to 30 years recruited for the CARDIA (Coronary Artery Risk Development in Young Adults) Study in 1985 through 1986 who were without hypertension before age 35 years. MEASUREMENTS: Blood pressure trajectories for each participant were estimated by using measurements from 7 examinations over the course of 20 years. Cumulative exposure to blood pressure in the prehypertension range (systolic blood pressure of 120 to 139 mm Hg, or diastolic blood pressure of 80 to 89 mm Hg) from age 20 to 35 years was calculated in units of mm Hg-years (similar to pack-years of tobacco exposure) and related to the presence of coronary calcium measured at each participant's last examination (mean age, 44 years [SD, 4]). RESULTS: Among 3560 participants, the 635 (18%) who developed prehypertension before age 35 years were more often black, male, overweight, and of lower socioeconomic status. Exposure to prehypertension before age 35 years, especially systolic prehypertension, showed a graded association with coronary calcium later in life (coronary calcium prevalence of 15%, 24%, and 38% for 0, 1 to 30, and >30 mm Hg-years of exposure, respectively; P < 0.001). This association remained strong after adjustment for blood pressure elevation after age 35 years and other coronary risk factors and participant characteristics. LIMITATION: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome. CONCLUSION: Prehypertension during young adulthood is common and is associated with coronary atherosclerosis 20 years later. Keeping systolic pressure below 120 mm Hg before age 35 years may provide important health benefits later in life.

Common beta-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease.

BACKGROUND: Previous studies suggest that beta-adrenergic receptor (betaAR) single nucleotide polymorphisms (SNPs) are associated with out-of-hospital sudden cardiac death (SCD) and overall mortality, but did not specifically examine risk of ventricular arrhythmias (VA). OBJECTIVE: This study examined the effects of functional SNPs of beta1AR and beta2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). METHODS: beta1AR (Ser49Gly, Arg389Gly) and beta2AR (Gly16Arg, Gln27Glu) SNPs were genotyped in a case-control study comparing 107 patients with CAD and aborted SCD due to VA with 287 CAD control subjects and 101 healthy control subjects. These variants were also examined in the Heart and Estrogen Replacement Study (HERS) cohort of women with CAD followed for SCD (n = 66) and nonfatal VA (NFVA) (n = 33) over 6.8 years. RESULTS: In the case-control study, no statistically significant association was observed for the odds of SCD with any of the SNPs or haplotypes tested. Similarly, HERS revealed null effects for these SNPs and haplotypes in relation to risk of SCD, SCD + NFVA, and all-cause mortality. Point estimates and confidence intervals for risk of SCD associated with beta2AR27 were similar in both populations (Glu27 carriers vs Gln27 homozygotes: adjusted odds ratio 1.23 [95% confidence interval 0.75 to 2.03, P = .41] in the case-control study, and adjusted relative risk (RR) 1.18 [95% confidence interval 0.69 to 2.00, P = .55] in HERS). These null findings trend in the opposite direction and differ from previous published estimates (P = .01 and .07, respectively). CONCLUSION: We did not find an increase in risk of SCD associated with any of these common betaAR polymorphisms.

Kidney dysfunction and sudden cardiac death among women with coronary heart disease.

We evaluated the association between kidney dysfunction and sudden cardiac death risk among ambulatory women with coronary heart disease. The Heart and Estrogen Replacement Study evaluated the effects of hormone treatment on cardiovascular events among 2763 postmenopausal women with coronary heart disease. Kidney dysfunction was categorized by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation. Multivariate proportional hazards models were used to adjust for cardiovascular risk factors, congestive heart failure, and myocardial infarction. At baseline, 37% (n=1027) had an eGFR of >60 mL/min, 54% (n=1503) had an eGFR of 40 to 60 mL/min, and 8% (n=230) had an eGFR of <40 mL/min. During the 6.8-year follow-up period, there were 136 adjudicated sudden cardiac deaths. The rate of sudden cardiac death was higher in those with lower kidney function (0.5% per year among those with an eGFR >60; 0.6% per year with an eGFR between 40 and 60; and 1.7% per year with an eGFR <40 mL/min; P for trend <0.001). After multivariate analysis with baseline risk factors, eGFR at 40 to 60 mL/min was not a significant predictor, but eGFR at <40 mL/min remained strongly associated with sudden cardiac death (hazard ratio: 3.2; 95% CI: 1.9 to 5.3); adjustment for incident congestive heart failure and myocardial infarction during follow-up diminished this association (hazard ratio: 2.3; 95% CI: 1.3 to 3.9), suggesting that congestive heart failure and myocardial infarction mediated only part of the association between kidney dysfunction and sudden cardiac death. Advanced kidney dysfunction is an independent predictor of sudden cardiac death among women with coronary heart disease.

Delineando a pesquisa clínica: uma abordagem epidemiológica / Designing clinical research: an epidemiologic approach

Um guia prático para o planejamento e a implementação da pesquisa clínica. Direto e de fácil leitura, o texto oferece a médicos e a investigadores clínicos descrições rigorosas dos componentes básicos, enfatizando o bom senso como o ingrediente fundamental do sucesso. Diferenciais dessa segunda edição: exemplos e idéias sobre o que há de novo na pesquisa clínica; expansão dos tópicos relativos ao delineamento e à implementação de ensaios clínicos randomizados; novas abordagens para estimativas de tamanho de amostra, abrangendo novas opções de delineamento; atualização nas questões éticas e na condução responsável da pesquisa clínica; novos capítulos sobre estudos de testes médicos, dados secundários (incluindo estudos suplementares e metanálise), gerenciamento de dados e pesquisa comunitária e internacional.

Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study.

OBJECTIVES: We sought to determine whether early adult levels of cardiovascular risk factors predict subsequent coronary artery calcium (CAC) better than concurrent or average 15-year levels and independent of a 15-year change in levels. BACKGROUND: Few studies have used multiple measures over the course of time to predict subclinical atherosclerosis. METHODS: African American and white adults, ages 18 to 30 years, in 4 U.S. cities were enrolled in the prospective CARDIA (Coronary Artery Risk Development in Young Adults) study from 1985 to 1986. Risk factors were measured at years 0, 2, 5, 7, 10, and 15, and CAC was assessed at year 15 (n = 3,043). RESULTS: Overall, 9.6% adults had any CAC, with a greater prevalence among men than women (15.0% vs. 5.1%), white than African American men (17.6% vs. 11.3%), and ages 40 to 45 years than 33 to 39 years (13.3% vs. 5.5%). Baseline levels predicted CAC presence (C = 0.79) equally as well as average 15-year levels (C = 0.79; p = 0.8262) and better than concurrent levels (C = 0.77; p = 0.019), despite a 15-year change in risk factor levels. Multivariate-adjusted odds ratios of having CAC by ages 33 to 45 years were 1.5 (95% confidence interval [CI] 1.3 to 1.7) per 10 cigarettes, 1.5 (95% CI 1.3 to 1.8) per 30 mg/dl low-density lipoprotein cholesterol, 1.3 (95% CI 1.1 to 1.5) per 10 mm Hg systolic blood pressure, and 1.2 (95% CI 1.1 to 1.4) per 15 mg/dl glucose at baseline. Young adults with above optimal risk factor levels at baseline were 2 to 3 times as likely to have CAC. CONCLUSIONS: Early adult levels of modifiable risk factors, albeit low, were equally or more informative about odds of CAC in middle age than subsequent levels. Earlier risk assessment and efforts to achieve and maintain optimal risk factor levels may be needed.

Objectively measured sleep characteristics among early-middle-aged adults: the CARDIA study.

Despite mounting evidence that sleep duration is a risk factor across diverse health and functional domains, little is known about the distribution and determinants of sleep. In 2003-2004, the authors used wrist activity monitoring and sleep logs to measure time in bed, sleep latency (time required to fall asleep), sleep duration, and sleep efficiency (percentage of time in bed spent sleeping) over 3 days for 669 participants at one of the four sites of the Coronary Artery Risk Development in Young Adults (CARDIA) study (Chicago, Illinois). Participants were aged 38-50 years, 58% were women, and 44% were Black. For the entire sample, mean time in bed was 7.5 (standard deviation (SD), 1.2) hours, mean sleep latency was 21.9 (SD, 29.0) minutes, mean sleep duration was 6.1 (SD, 1.2) hours, and mean sleep efficiency was 80.9 (SD, 11.3)%. All four parameters varied by race-sex group. Average sleep duration was 6.7 hours for White women, 6.1 hours for White men, 5.9 hours for Black women, and 5.1 hours for Black men. Race-sex differences (p < 0.001) remained after adjustment for socioeconomic, employment, household, and lifestyle factors and for apnea risk. Income was independently associated with sleep latency and efficiency. Sleep duration and quality, which have consequences for health, are strongly associated with race, sex, and socioeconomic status.

Incidence and antecedents of nonmedical prescription opioid use in four US communities. The Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study.

BACKGROUND: Nonmedical use of prescription opioids has emerged as a major public health problem during the last decade, but direct measures of incidence and predisposing factors are lacking. METHODS: We prospectively measured incidence and antecedents of nonmedical prescription opioid use in The Coronary Artery Risk Development in Young Adults study among 28-40-year-old African- and European-American men and women with no prior history of nonmedical opioid use. RESULTS: Among 3163 participants, 23 reported new nonmedical prescription opioid use in 2000-2001 (5-year incidence 0.7%; 95%CI: 0.4-1.0%). All 23 had previously reported marijuana use (p<0.001). Five-year incidence was significantly higher among European-American men (OR=3.3; 95%CI: 1.3-8.3), and among participants reporting a history of amphetamine use (OR=24; 95%CI: 6.9-83) or medical opioid use for treatment of pain (OR=8.6; 95%CI: 2.5-30). These associations remained strong when examined among marijuana users and after adjusting for demographics, social factors, and other antecedent substance use. Amphetamine use was the best single predictor of future nonmedical use (sensitivity 87%, specificity 79%). CONCLUSIONS: Initiation of nonmedical prescription opioid use is generally rare in 28-40-year-old adults, but is observed to be more common with a previous history of substance abuse and legal access to opioids through prescription by a physician.

Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study.

Although statins are effective lipid-lowering agents, the phenotypic and demographic predictors of such lowering have been less well examined. We enrolled 944 African-American and white men and women who completed an open-label, 6-week pharmacogenetics trial of 40 mg of simvastatin. The phenotypic and demographic variables were examined as predictors of the change in lipids and lipoproteins using linear regression analysis. On average, treatment with simvastatin lowered low-density lipoprotein (LDL) cholesterol by 54 mg/dl and increased high-density lipoprotein (HDL) cholesterol by 2 mg/dl. Compared with African-Americans, whites had a 3-mg/dl greater LDL reduction and a 1-mg/dl higher HDL elevation, independent of other variables, including baseline lipoprotein levels (p <0.01). Multivariate analyses revealed moderate subgroup differences, with older participants having a larger decrease in LDL cholesterol and apolipoprotein B levels compared with younger participants (p <0.001), women having larger increases in HDL than men (p <0.01), nonsmokers having larger decreases in LDL and triglyceride levels compared with smokers (p <0.05), those with hypertension having smaller decreases in apolipoprotein B than those without hypertension (p <0.05), and those with a larger waist circumference having a diminished lowering of triglycerides in response to treatment with simvastatin (p <0.01). In conclusion, treatment with simvastatin produced favorable lipid and lipoprotein changes among all participants. The magnitude of the lipid and lipoprotein responses, however, differed among participants according to a number of phenotypic and demographic characteristics.

C-reactive protein concentration and incident hypertension in young adults: the CARDIA study.

BACKGROUND: There is increasing evidence that C-reactive protein (CRP) concentration, a measure of inflammation, is an independent risk factor for the development of hypertension in older adults. However, it is unknown whether a similar relationship exists in younger individuals. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study was initiated in 1985-1986 to determine the factors that are associated with coronary risk development in young adults. C-reactive protein concentrations were measured in 3919 African American and white men and women enrolled in CARDIA using blood specimens from the year 7 examination (1992-1993), when the age of the cohort was 25 to 37 years, and the year 15 examination (2000-2001). RESULTS: In unadjusted analyses, CRP concentrations greater than 3 mg/L, compared with those less than 1 mg/L, was associated with a 79% greater risk of incident hypertension (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.40-2.28). However, CRP concentration did not predict risk of incident hypertension after adjusting for year 7 body mass index (BMI) (OR, 1.14; 95% CI, 0.86-1.53) or year 7 BMI and other potential confounders (OR, 1.13; 95% CI, 0.83-1.52). In addition, year 7 CRP concentration was not associated with change in systolic or diastolic blood pressure after adjusting for BMI (P = .10 and P = .70, respectively). These findings were similar within each of the race- and sex-specific groups. CONCLUSION: C-reactive protein is associated with hypertension in young adults, but in contrast to the finding in older populations, the association is no longer present after adjusting for BMI.