Prevalence of Elevated Cardiovascular Risks in Young Adults: A Cross-sectional Analysis of National Health and Nutrition Examination Surveys

Background: The 2013 cholesterol management guidelines from the American College of Cardiology and American Heart Association (ACC/AHA) recommend lipid screening in all adults older than 20 years to identify those at increased risk for atherosclerotic cardiovascular disease (ASCVD). Statins may be considered for patients with elevated 10-year risk (>5%) or a low-density lipoprotein cholesterol (LDL-C) level of 4.92 mmol/L (190 mg/dL) or greater. Objective: To describe the prevalence of elevated ASCVD risk among nondiabetic adults younger than 50 years. Design: Cross-sectional. Setting: NHANES (National Health and Nutrition Examination Survey), 1999 to 2000 through 2011 to 2012. Participants: Adults aged 30 to 49 years without known ASCVD or diabetes. Measurements: 10-year ASCVD risk was estimated by using the 2013 ACC/AHA ASCVD risk calculator. Participants were subdivided by age, sex, and history of smoking and hypertension. The percentages of adults in each subgroup with a 10-year ASCVD risk greater than 5% and of those with an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater were estimated. Low-prevalence subgroups were defined as those in which a greater than 1% prevalence of elevated cardiovascular risk could be ruled out (that is, the upper 95% confidence bound for prevalence was ≤1%). Results: Overall, 9608 NHANES participants representing 67.9 million adults were included, with approximately half (47.12%, representing 32 million adults) in low-prevalence subgroups. In the absence of smoking or hypertension, 0.09% (95% CI, 0.02% to 0.35%) of adult men younger than 40 years and 0.04% (CI, 0.0% to 0.26%) of adult women younger than 50 years had an elevated risk. Among other subgroups, 0% to 75.9% of participants had an increased risk. Overall, 2.9% (CI, 2.3% to 3.5%) had an LDL-C level of 4.92 mmol/L (190 mg/dL) or greater. Limitation: No information was available regarding cardiovascular outcomes. Conclusion: In the absence of risk factors, the prevalence of increased ASCVD risk is low among women younger than 50 and men younger than 40 years. Primary Funding Source: None.

Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 165, No 11

The U.S. Preventive Services Task Force (USPSTF) recently issued guidelines on screening for vitamin D deficiency. The guidelines were based on randomized trials of vitamin D deficiency screening and treatment, as well as on case–control studies nested within the Women's Health Initiative. The USPSTF concluded that current evidence is insufficient to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. Compared with placebo or no treatment, vitamin D was associated with decreased mortality; however, benefits were no longer seen after trials of institutionalized persons were excluded. Vitamin D treatment was associated with a possible decreased risk for at least 1 fall and the total number of falls per person but not for fractures. None of the studies examined the effects of vitamin D screening versus not screening on clinical outcomes. In this Grand Rounds, 2 prominent endocrinologists debate the issue of screening for vitamin D deficiency in a 55-year-old, asymptomatic, postmenopausal woman. They review the data on which the USPSTF recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of screening for vitamin D deficiency in primary care practice.

Development of the SaFETy Score: A Clinical Screening Tool for Predicting Future Firearm Violence Risk

Background: Interpersonal firearm violence among youth is a substantial public health problem, and emergency department (ED) physicians require a clinical screening tool to identify high-risk youth. Objective: To derive a clinically feasible risk index for firearm violence. Design: 24-month prospective cohort study. Setting: Urban, level 1 ED. Participants: Substance-using youths, aged 14 to 24 years, seeking ED care for an assault-related injury and a proportionately sampled group of non–assault-injured youth enrolled from September 2009 through December 2011. Measurements: Firearm violence (victimization/perpetration) and validated questionnaire items. Results: A total of 599 youths were enrolled, and presence/absence of future firearm violence during follow-up could be ascertained in 483 (52.2% were positive). The sample was randomly split into training (75%) and post–score-construction validation (25%) sets. Using elastic-net penalized logistic regression, 118 baseline predictors were jointly analyzed; the most predictive variables fell predominantly into 4 domains: violence victimization, community exposure, peer influences, and fighting. By selection of 1 item from each domain, the 10-point SaFETy (Serious fighting, Friend weapon carrying, community Environment, and firearm Threats) score was derived. SaFETy was associated with firearm violence in the validation set (odds ratio [OR], 1.47 [95% CI, 1.23 to 1.79]); this association remained (OR, 1.44 [CI, 1.20 to 1.76]) after adjustment for reason for ED visit. In 5 risk strata observed in the training data, firearm violence rates in the validation set were 18.2% (2 of 11), 40.0% (18 of 45), 55.8% (24 of 43), 81.3% (13 of 16), and 100.0% (6 of 6), respectively. Limitations: The study was conducted in a single ED and involved substance-using youths. SaFETy was not externally validated. Conclusion: The SaFETy score is a 4-item score based on clinically feasible questionnaire items and is associated with firearm violence. Although broader validation is required, SaFETy shows potential to guide resource allocation for prevention of firearm violence. Primary Funding Source: National Institute on Drug Abuse R01024646.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-sectional Analysis of Two Cohort Studies: Annals of Internal Medicine: Vol 166, No 9

Background: The relationship between body weight and cardiometabolic disease may vary substantially by race/ethnicity. Objective: To determine the prevalence and correlates of the phenotype of metabolic abnormality but normal weight (MAN) for 5 racial/ethnic groups. Design: Cross-sectional analysis. Setting: 2 community-based cohorts. Participants: 2622 white, 803 Chinese American, 1893 African American, and 1496 Hispanic persons from MESA (Multi-Ethnic Study of Atherosclerosis) and 803 South Asian participants in the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study. Measurements: Prevalence of 2 or more cardiometabolic abnormalities (high fasting glucose, low high-density lipoprotein cholesterol, and high triglyceride levels and hypertension) among normal-weight participants was estimated. Correlates of MAN were assessed by using log-binomial models. Results: Among normal-weight participants (n = 846 whites, 323 Chinese Americans, 334 African Americans, 252 Hispanics, and 195 South Asians), the prevalence of MAN was 21.0% (95% CI, 18.4% to 23.9%) in whites, 32.2% (CI, 27.3% to 37.4%) in Chinese Americans, 31.1% (CI, 26.3% to 36.3%) in African Americans, 38.5% (CI, 32.6% to 44.6%) in Hispanics, and 43.6% (CI, 36.8% to 50.6%) in South Asians. Adjustment for demographic, behavioral, and ectopic body fat measures did not explain racial/ethnic differences. After adjustment for age, sex, and race/ethnicity–body mass index (BMI) interaction, for the equivalent MAN prevalence at a BMI of 25.0 kg/m2 in whites, the corresponding BMI values were 22.9 kg/m2 (CI, 19.5 to 26.3 kg/m2) in African Americans, 21.5 kg/m2 (CI, 18.5 to 24.5 kg/m2) in Hispanics, 20.9 kg/m2 (CI, 19.7 to 22.1 kg/m2) in Chinese Americans, and 19.6 kg/m2 (CI, 17.2 to 22.0 kg/m2) in South Asians. Limitation: Cross-sectional study design and lack of harmonized dietary data between studies. Conclusion: Compared with whites, all racial/ethnic minority groups had a statistically significantly higher prevalence of MAN, which was not explained by demographic, behavioral, or ectopic fat measures. Using a BMI criterion for overweight to screen for cardiometabolic risk may result in a large proportion of racial/ethnic minority groups being overlooked. Primary Funding Source: National Institutes of Health.

Are Microbial Politics Local?

Detecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment: A Modeling Study of Randomized Clinical Trials: Annals of Internal Medicine: Vol 166, No 5

Background: Two recent randomized trials produced discordant results when testing the benefits and harms of treatment to reduce blood pressure (BP) in patients with cardiovascular disease (CVD). Objective: To perform a theoretical modeling study to identify whether large, clinically important differences in benefit and harm among patients (heterogeneous treatment effects [HTEs]) can be hidden in, and explain discordant results between, treat-to-target BP trials. Design: Microsimulation. Data Sources: Results of 2 trials comparing standard (systolic BP target <140 mm Hg) with intensive (systolic BP target <120 mm Hg) BP treatment and data from the National Health and Nutrition Examination Survey (2013 to 2014). Target Population: U.S. adults. Time Horizon: 5 years. Perspective: Societal. Intervention: BP treatment. Outcome Measures: CVD events and mortality. Results of Base-Case Analysis: Clinically important HTEs could explain differences in outcomes between 2 trials of intensive BP treatment, particularly diminishing benefit with each additional BP agent (for example, adding a second agent reduces CVD risk [hazard ratio, 0.61], but adding a fourth agent to a third has no benefit) and increasing harm at low diastolic BP. Results of Sensitivity Analysis: Conventional treat-to-target trial designs had poor (<5%) statistical power to detect the HTEs, despite large samples (n > 20 000), and produced biased effect estimates. In contrast, a trial with sequential randomization to more intensive therapy achieved greater than 80% power and unbiased HTE estimates, despite small samples (n = 3500). Limitations: The HTEs as a function of the number of BP agents only were explored. Simulated aggregate data from the trials were used as model inputs because individual-participant data were not available. Conclusion: Clinically important heterogeneity in intensive BP treatment effects remains undetectable in conventional trial designs but can be detected in sequential randomization trial designs. Primary Funding Source: National Institutes of Health and U.S. Department of Veterans Affairs.

Lack of Evidence Linking Calcium With or Without Vitamin D Supplementation to Cardiovascular Disease in Generally Healthy Adults: A Clinical Guideline From the National Osteoporosis Foundation and the American Society for Preventive Cardiology

Description: Calcium is the dominant mineral present in bone and a shortfall nutrient in the American diet. Supplements have been recommended for persons who do not consume adequate calcium from their diet as a standard strategy for the prevention of osteoporosis and related fractures. Whether calcium with or without vitamin D supplementation is beneficial or detrimental to vascular health is not known. Methods: The National Osteoporosis Foundation and American Society for Preventive Cardiology convened an expert panel to evaluate the effects of dietary and supplemental calcium on cardiovascular disease based on the existing peer-reviewed scientific literature. The panel considered the findings of the accompanying updated evidence report provided by an independent evidence review team at Tufts University. Recommendation: The National Osteoporosis Foundation and American Society for Preventive Cardiology adopt the position that there is moderate-quality evidence (B level) that calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) to the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time. In light of the evidence available to date, calcium intake from food and supplements that does not exceed the tolerable upper level of intake (defined by the National Academy of Medicine as 2000 to 2500 mg/d) should be considered safe from a cardiovascular standpoint.

Calibration of the Pooled Cohort Equations for Atherosclerotic Cardiovascular Disease: An Update: Annals of Internal Medicine: Vol 165, No 11

The latest guidelines from the American College of Cardiology and American Heart Association, released in fall 2013, provide a long-anticipated update to the recommendations of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). The guidelines incorporate a new risk score for atherosclerotic cardiovascular disease that includes stroke as well as coronary heart disease. After publication, the new pooled cohort equations (PCEs) were evaluated in 15 studies from the United States and Europe, most of which used cohorts that were more contemporary than those used in developing the guidelines. In almost all of these external validation cohorts, the PCEs overestimated the observed risk. This narrative review provides an update of the published reports, an overview of the strengths and weaknesses of these validation efforts, and a discussion of possible reasons for the discrepancies. These issues may be useful in a recalibration process designed to better match predicted and observed risks relevant for current clinical practice.

Can Knowledge About Heterogeneity in Treatment Effects Help Us Choose Wisely?

High Generic Drug Prices and Market Competition: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 167, No 3

Background: Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. Objective: To determine the association between market competition levels and the change in generic drug prices in the United States. Design: Retrospective cohort study. Setting: Prescription claims from commercial health plans between 2008 and 2013. Measurements: The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl–Hirschman Index (HHI)—calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market—and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. Results: From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of −31.7% (95% CI, −34.4% to −28.9%), −11.8% (CI, −18.6% to −4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. Limitation: Study findings may not be generalizable to drugs that became generic after 2008. Conclusion: Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. Primary Funding Source: None.