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Most people who develop coronary artery disease have at least one risk factor, according to researchers who analyzed data from three studies that followed 386,915 people for up to 30 years. Over 87% of those who eventually developed coronary artery disease had at least one risk factor, including diabetes, smoking, high blood pressure, or high cholesterol levels.

Importance: Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older.Objective: To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older.Design, Setting, and Participants: Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics.Exposures: Any new statin prescription.Main Outcomes and Measures: The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention).Results: Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers.Conclusions and Relevance: Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD. [ABSTRACT FROM AUTHOR]

Elevated blood levels of insulin appears to cause excessive blood clotting, which could explain why diabetics have an increased risk of heart disease. In a study of approximately 3,000 people in the Framingham Offspring Study, those with elevated insulin levels also had elevated blood levels of proteins involved in blood clotting and low levels of proteins that break up blood clots. This was true even in people with normal blood sugar metabolism.

The article discusses a study which investigated the association between metformin use and mortality among patients with diabetes and atherothrombosis. A total of 19,691 diabetic patients with established atherothrombosis were observed between December 2003 and December 2004. Mortality rates among diabetic users and nonusers of metformin showed that the use of metformin as a secondary prevention may decrease mortality among patients with diabetes. No interaction effect on mortality was shown between metformin use and the number of diseased arterial beds.

The article details a study which examined the determinants of four-year cardiovascular event rates in outpatients with or at risk of atherothrombosis. Patients considered for the study were those diagnosed with coronary artery disease, cerebrovascular disease or peripheral arterial disease and those with multiple risk factors for atherothrombosis. Of the total 45,227 study participants, 2,315 died of cardiovascular reasons, 1,228 developed myocardial infarction and 1,898 experienced stroke. Study authors concluded that clinical descriptors are relevant in identifying patients at high risk of cardiovascular events.

The article presents research assessing cardiovascular disease (CVD) risk factors among active National Football League (NFL) players in comparison with data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. The design of the cross-sectional study involving 504 active NFL players and men from the general U.S. population is described. The outcomes measured included the prevalence of CVD risk factors such as dyslipidemia, hypertension, smoking, and glucose intolerance. Results suggest that larger NFL players had a higher prevalence of hypertension, while increased body mass index was associated with increased CVD risk factors in both populations.

The article presents a study which examines the race- and sex-specific epidemiology of incident heart failure (HF) in a contemporary elderly cohort. The researchers investigate the incidence of HF, the population-attributable risk (PAR) for HF, and outcomes of incident HF among 2,934 participant with HF who enrolled in the Health, Aging, and Body Composition Study. The study shows that incident HF is common in old persons in which a large proportion of risk is attributed to modifiable risk factors.

This article presents the results of a study comparing the performance of different lipid measures for coronary heart disease (CHD) prediction using discrimination and calibration characteristics and reclassification of risk categories to assess incremental utility of apolipoproteins (apo) over traditional lipids for CHD prediction. The study used a large population-based cohort and discovered that the overall performance of apo B and apo A-1 ratio for prediction of CHD was comparable with that of traditional lipid ratios but did not offer incremental utility over low density lipoprotein cholesterol (HDL-C). The data does not support measurement of apo B or apo A-1 in clinical practice when total cholesterol and HDL-C measurements are available.

The article reports on a study which estimated the seven-year risk of type 2 diabetes mellitus (T2DM) in middle-aged people who had an oral glucose tolerance test at baseline. Results indicated that obesity, parental diabetes, and metabolic syndrome traits were effective predictors T2DM risk in a middle-aged white population. A simple T2DM forecasting algorithm was developed.

Background: Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. Objective: To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. Design, Setting, and Participants: A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. Main Outcome Measures: Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all cause dementia and Alzheimer disease according to baseline plasma levels. Results: Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the followup. After adjustment for age, sex, apolipoprotein E e4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all cause dementia (95% confidence interval, 0.29-0.97; P=.04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P=.14). Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P<.001) in a subset of 488 participants. We found no other significant associations. Conclusion: The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study. [ABSTRACT FROM AUTHOR]

Context Atherothrombosis is the leading cause of cardiovascular morbidity and mortality around the globe. To date, no single international database has characterized the atherosclerosis risk factor profile or treatment intensity of individuals with atherothrombosis. Objective To determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world. Design, Setting, and Participants The Reduction of Atherothrombosis for Continued Health (REACH) Registry collected data on atherosclerosis risk factors and treatment. A total of 67 888 patients aged 45 years or older from 5473 physician practices in 44 countries had either established arterial disease (coronary artery disease [CAD], n = 40 258; cerebrovascular disease, n = 18 843; peripheral arterial disease, n = 8273) or 3 or more risk factors for atherothrombosis (n = 12 389) between 2003 and 2004. Main Outcome Measures Baseline prevalence of atherosclerosis risk factors, medication use, and degree of risk factor control. Results Atherothrombotic patients throughout the world had similar risk factor profiles: a high proportion with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%). The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%) were similar in most geographic locales, but was highest in North America (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P<.001 vs other regions). Patients were generally undertreated with statins (69.4% overall; range: 56.4% for cerebrovascular disease to 76.2% for CAD), antiplatelet agents (78.6% overall; range: 53.9% for 3 risk factors to 85.6% for CAD), and other evidence-based risk reduction therapies. Current tobacco use in patients with established vascular disease was substantial (14.4%). Undertreated hypertension (50.0% with elevated blood pressure at baseline), undiagnosed hyperglycemia (4.9%), and impaired fasting glucose (36.5% in those not known to be diabetic) were common. Among those with symptomatic atherothrombosis, 15.9% had symptomatic polyvascular disease. Conclusion This large, international, contemporary database shows that classic cardiovascular risk factors are consistent and common but are largely undertreated and undercontrolled in many regions of the world. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Determination of C-reactive protein (CRP) level has been suggested to improve cardiovascular disease (CVD) risk assessment. This study examines the utility of CRP levels to assess CVD risk in a community setting. Methods We performed a prospective observational cohort study on a community population sample. A total of 1949 men and 2497 women without CVD from the Framingham Heart Study underwent CVD risk factor assessment. Initial CVD events during 8 years of follow-up were recorded. Results There were 283 major CVD and 160 major coronary heart disease incident events. Age-, sex-, and multivariable-adjusted analyses generally used CRP level categories of less than 1, 1 to 3, and greater than 3 mg/L. In age- and sex-adjusted models, the traditional risk factors and elevated CRP levels indicated increased risk. The age- and sex-adjusted relative risk (RR) and 95% confidence interval (CI) of CRP level greater than 3 mg/L for major CVD was elevated (RR, 1.60; 95% CI, 1.19-2.14), with evidence of attenuation (RR, 1.22; 95% CI, 0.90-1.66) in multivariable models. The C statistic, a measure of the discriminatory capability of the prediction models, was 0.74 for prediction of major CVD with age and CRP level. In multivariable models that included traditional risk factors, the C statistic was 0.78, a value that was unchanged with the addition of CRP to the multivariable model. Similar relations were noted for major coronary heart disease events. Conclusion Elevated CRP level provided no further prognostic information beyond traditional office risk factor assessment to predict future major CVD and major coronary heart disease in this population sample. [ABSTRACT FROM AUTHOR]

Context Despite reductions in cardiovascular disease (CVD) mortality over the past few decades, it is unclear whether adults with and without diabetes have experienced similar declines in CVD risk. Objective To determine whether adults with and without diabetes experienced similar declines in incident CVD in 1950-1995. Design, Setting, and Participants Participants aged 45-64 years from the Framingham Heart Study original and offspring cohorts who attended examinations in 1950-1966 (“earlier” time period; 4118 participants, 113 with diabetes) and 1977-1995 (“later” time period; 4063 participants, 317 with diabetes). Incidence rates of CVD among those with and without diabetes were compared between the earlier and later periods. Main Outcome Measures Myocardial infarction, coronary heart disease death, and stroke. Results Among participants with diabetes, the age- and sex-adjusted CVD incidence rate was 286.4 per 10 000 person-years in the earlier period and 146.9 per 10 000 in the later period, a 49.3% (95% confidence interval [CI], 16.7%-69.4%) decline. Among participants without diabetes, the age- and sex-adjusted incidence rate was 84.6 per 10 000 person-years in the earlier period and 54.3 per 10 000 person-years in the later period, a 35.4% (95% CI, 25.3%-45.4%) decline. Hazard ratios for diabetes as a predictor of incident CVD were not different in the earlier vs later periods. Conclusions We report a 50% reduction in the rate of incident CVD events among adults with diabetes, although the absolute risk of CVD is 2-fold greater than among persons without diabetes. Adults with and without diabetes have benefited similarly during the decline in CVD rates over the last several decades. More aggressive treatment of CVD risk factors and further research on diabetes-specific factors contributing to CVD risk are needed to further reduce the high absolute risk of CVD still experienced by persons with diabetes. [ABSTRACT FROM AUTHOR]

Context The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations. Objective To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS). Design, Setting, and Participants The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years. Main Outcome Measures "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions. Results The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort. Conclusions The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice. [ABSTRACT FROM AUTHOR]

Context Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. Objective To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. Design Inception cohort study. Setting Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. Participants All Framingham Offspring Study participants (aged ≥30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. Main Outcome Measures We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. Results Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. Conclusions Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adult... [ABSTRACT FROM AUTHOR]

Context: Kidney disease is associated with an increased risk for the development of cardiovascular disease and end-stage renal disease; however, risk factors for kidney disease have not been well studied. Objective: To identify predictors of the development of new-onset kidney disease. Design, Setting, and Participants: A community-based, longitudinal cohort study of 2585 participants who attended both a baseline examination in 1978-1982 and a follow-up examination in 1998-2001, and who were free of kidney disease at baseline. Main Outcome Measures: Kidney disease was assessed by the Modification of Diet in Renal Disease Study equation and defined by a glomerular filtration rate (GFR) in the fifth or lower percentile (≤59.25 mL/min per 1.73 m[sup 2] in women, ≤64.25 mL/min per 1.73 m[sup 2] in men). Stepwise logistic regression was used to determine the impact of risk factors on the occurrence of new-onset kidney disease. Baseline and long-term, 12-year, averaged risk factor models were explored. Results: At baseline, there were 1223 men and 1362 women, with a mean age of 43 years, who were free of preexisting kidney disease. After a mean follow-up of 18.5 years, 244 participants (9.4%) had developed kidney disease. In multivariable models, baseline age (odds ratio [OR], 2.36 per 10-year increment; 95% confidence interval [CI], 2.00-2.78), GFR (<90 mL/min per 1.73 m[sup 2]: OR, 3.01; 95% CI, 1.98-4.58; 90-119 mL/min per 1.73 m[sup 2]: OR, 1.84; 95% CI, 1.16-2.93), body mass index (OR, 1.23 per 1 SD; 95% CI, 1.08-1.41), diabetes (OR, 2.60; 95% CI, 1.44-4.70), and smoking (OR, 1.42; 95% CI, 1.06-1.91) were related to the development of kidney disease. In addition to baseline age and GFR, the long-term, averaged risk factors that were predictive of kidney disease included hypertension (OR, 1.57; 95% CI, 1.17-2.12), high-density lipoprotein cholesterol level (OR, 0.80 per 1 SD; 95% CI, 0.69-0.92), and diabetes (OR, 2.38; 95% CI, 1.45-3.92). Compared w... [ABSTRACT FROM AUTHOR]

Background: Previous studies examining the association of plasma cholesterol levels with the risk for development of Alzheimer disease (AD) have been inconclusive. We examined the impact of baseline and lifetime plasma total cholesterol levels averaged across many years on the risk for AD in a large, population-based cohort. Methods: Five thousand two hundred nine subjects from the Framingham Study original cohort underwent biennial evaluation for cardiovascular risk factors since 1950, with estimations of serum total cholesterol levels at 19 of these 25 biennial examinations. The study sample consisted of 1026 subjects from this cohort who were alive and free of stroke and dementia at examination cycle 20 (1988-1989) and had undergone apolipoprotein E (APOE) genotyping. The main outcome measure was incident AD diagnosed using standard criteria, according to average total cholesterol levels across biennial examination cycles 1 to 15 and baseline total cholesterol level measured at the 20th biennial examination cycle. Results: Alzheimer disease developed in 77 subjects from 1992 to 2000. After adjustment for age, sex, APOE genotype, smoking, body mass index (calculated as weight in kilograms divided by the square of height in meters), coronary heart disease, and diabetes, we found no significant association between the risk for incident AD and average cholesterol level at biennial examination cycles 1 to 15 (hazard ratio per 10-mg/dL [0.3-mmol/L] rise, 0.95; 95% confidence interval, 0.87-1.04) or baseline total cholesterol level at examination 20 (hazard ratio, 0.97; 95% confidence interval, 0.90-1.05). Conclusion: In this large, population-based cohort, baseline and long-term average serum total cholesterol levels were not associated with the risk for incident AD. [ABSTRACT FROM AUTHOR]

Context: Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF). Objective: To study prospectively the association between nonfasting plasma homocysteine and incidence of CHF. Design, Setting, and Participants: Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial infarction (recognized or unrecognized) at baseline. Main Outcome Measure: Incidence of a first episode of CHF during an 8-year follow-up period. Results: During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women. Conclusions: An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, no single investigation concerning the long-term effects of overweight status on the risk for hypertension, hypercholesterolemia, diabetes mellitus, and cardiovascular sequelae has been reported. Methods: Relations between categories of body mass index (BMI), cardiovascular disease risk factors, and vascular disease end points were examined prospectively in Framingham Heart Study participants aged 35 to 75 years, who were followed up to 44 years. The primary outcome was new cardiovascular disease, which included angina pectoris, myocardial infarction, coronary heart disease, or stroke. Analyses compared overweight (BMI [calculated as weight in kilograms divided by the square of height in meters], 25.0-29.9) and obese persons (BMI ≥30) to a referent group of normal-weight persons (BMI, 18.5-24.9). Results: The age-adjusted relative risk (RR) for new hypertension was highly associated with overweight status (men: RR, 1.46; women: RR, 1.75). New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity. The age-adjusted RR (confidence interval [CI]) for cardiovascular disease was increased among those who were overweight (men: 1.21 [1.05-1.40]; women: 1.20 [1.03-1.41]) and the obese (men: 1.46 [1.20-1.77];women: 1.64 [1.37-1.98]). High population attributable risks were related to excess weight (BMI ≥25) for the outcomes hypertension (26% men; 28% women), angina pectoris (26% men; 22% women), and coronary heart disease (23% men; 15% women). Conclusions: The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae. Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level. [ABSTRACT FROM AUTHOR]

Context: Several reports have suggested the usefulness of plasma brain natriuretic peptide (BNP) as a screening test for left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD). Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women. Objectives: To examine the usefulness of natriuretic peptides for screening for elevated LV mass and LVSD in the community. Design, Setting, and Participants: Community-based prospective cohort study of 3177 participants (1707 women) from the Framingham Study who attended a routine examination in 1995-1998. Main Outcome Measures: Receiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values, and likelihood ratios for identifying elevated LV mass (sex-specific 90th percentile or higher of LV mass/[height][sup 2]), LVSD (ejection fraction ≤50% and/or fractional shortening <29%), and moderate to severe LVSD (ejection fraction ≤40% and/or fractional shortening <22%) at different discrimination limits of plasma BNP and N-terminal proatrial natriuretic peptide (NT-ANP), with echocardiography as the criterion standard. Results: The areas under the ROC curves for elevated LV mass or LVSD were at or below 0.75 for both peptides, were higher for men compared with women, and were similar for BNP and NT-ANP. The diagnostic performance of natriuretic peptides for LVSD improved in women but not in men when select high-risk subgroups were targeted. Discrimination limits based on high specificity (0.95) yielded better positive predictive values and likelihood ratios compared with age- and sex-specific reference limits yet only identified less than one third of participants who had elevated LV mass or LVSD. Conclusion: In our large community-based sample, the performance of BNP and NT-ANP for detection of elevated LV mass and LVSD was suboptimal, suggesting limited usefulness... [ABSTRACT FROM AUTHOR]

The article revisits the effectiveness of statins in the treatment and prevention of cardiovascular disease. A number of randomized trials suggested that statin therapy may no longer be optimal for patient care. Physicians are advised to consider that the use of statin therapy should be associated with lifestyle interventions such as diet, exercise and smoking cessation. In addition, the article warns about the continued use of absolute risk assessment to guide statin prescription.

An introduction is presented in which the editor discusses various articles within the issue on topics including risk factors of cardiovascular disease, use of coronary artery calcium as risk markers and reclassification methods in risk prediction.

The author comments on a study by I. Tzoulaki et al on scientific literature concerning efforts to improve the prediction of coronary heart disease (CHD) over and above the Framingham risk score. A set of variables for the study has been developed by researchers, including age, sex, systolic blood pressure, cholesterol level, diabetes mellitus and current smoking. The author stresses the significance of including newer variables to improve CHD prediction and prevention strategies. Also cited is recalibrating a CHD risk prediction equation.

Details two meta-analyses reviewing risks of coronary heart disease (CHD) related to blood levels of homocysteine and methylene tetrahydrofolate reductase (MTHFR). Description of Homocysteine Studies Collaboration on the correlation between homocysteine levels and risk of CHD; Role of MTHFR gene in the occurrence of CHD.

A response from the authors of the article "A Trial-Based Approach to Statin Guidelines" in the 2013 issue is presented.

A response by Robert M. Najarian, Lisa M. Sullivan, William B. Kannel, Peter W. F. Wilson, Ralph B. D'Agostino, and Philip A. Wolf to a letter to the editor about his article "Metabolic syndrome compared with type 2 diabetes mellitus as a risk factor for stroke: the Framingham Offspring Study" in an earlier 2006 issue is presented.

A response by Peter W. F. Wilson to a comment about his article on C-reactive protein is presented.

Importance: Primary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation., Objective: To determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population., Design, Setting, and Participants: This was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023., Exposures: PRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status., Main Outcomes and Measures: Incident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events., Results: A total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, -0.07% to 3.30%)., Conclusions and Relevance: Study results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear., Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19., Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021., Exposures: The hemoglobin beta S (HbS) allele (rs334-T)., Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records., Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure., Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

Context: Few data document current cardiovascular (CV) event rates in stable patients with atherothrombosis in a community setting. Differential event rates for patients with documented coronary artery disease (CAD), cerebrovascular disease (CVD), or peripheral arterial disease (PAD) or those at risk of these diseases have not been previously evaluated in a single international cohort., Objective: To establish contemporary, international, 1-year CV event rates in outpatients with established arterial disease or with multiple risk factors for atherothrombosis., Design, Setting, and Participants: The Reduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68 236 patients with either established atherosclerotic arterial disease (CAD, PAD, CVD; n = 55 814) or at least 3 risk factors for atherothrombosis (n = 12 422), who were enrolled from 5587 physician practices in 44 countries in 2003-2004., Main Outcome Measures: Rates of CV death, myocardial infarction (MI), and stroke., Results: As of July 2006, 1-year outcomes were available for 95.22% (n = 64 977) of participants. Cardiovascular death, MI, or stroke rates were 4.24% overall: 4.69% for those with established atherosclerotic arterial disease vs 2.15% for patients with multiple risk factors only. Among patients with established disease, CV death, MI, or stroke rates were 4.52% for patients with CAD, 6.47% for patients with CVD, and 5.35% for patients with PAD. The incidences of the end point of CV death, MI, or stroke or of hospitalization for atherothrombotic event(s) were 15.20% for CAD, 14.53% for CVD, and 21.14% for PAD patients with established disease. These event rates increased with the number of symptomatic arterial disease locations, ranging from 5.31% for patients with risk factors only to 12.58% for patients with 1, 21.14% for patients with 2, and 26.27% for patients with 3 symptomatic arterial disease locations (P<.001 for trend)., Conclusions: In this large, contemporary, international study, outpatients with established atherosclerotic arterial disease, or at risk of atherothrombosis, experienced relatively high annual CV event rates. Multiple disease locations increased the 1-year risk of CV events.

Context: The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations., Objective: To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS)., Design, Setting, and Participants: The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years., Main Outcome Measures: "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions., Results: The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort., Conclusions: The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice.