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Left ventricular hypertrophy (LVH) is an independent, modifiable risk factor for cardiovascular disease. However, current screening strategies are limited. In 2478 participants without clinical disease from the Dallas Heart Study, we evaluated a multimarker screening strategy that complements electrocardiographic (ECG) criteria for LVH with 2 biomarkers, amino-terminal pro-B-type natriuretic peptide and highly sensitive cardiac troponin T. An integer LVH risk score from 0 to 3 was determined as the sum of the following: (1) LVH by Sokolow-Lyon ECG; (2) amino-terminal pro-B-type natriuretic peptide in the highest sex-specific quartile; and (3) detectable cardiac troponin T. Cardiac magnetic resonance imaging-determined LVH served as the primary outcome. The probability of LVH increased from 2% with an LVH risk score of 0 to 50% with a score of 3 (P0.001). Sokolow-Lyon ECG afforded low sensitivity (26% [95% confidence interval {CI}, 17-32%]) and high specificity (96% [95% CI, 95-97%]), whereas a risk score ≥2 offered higher sensitivity (44% [95% CI, 34-51%]) with good specificity (90% [95% CI, 89-93%]) and a score threshold of 1 offered reasonable sensitivity (76% [95% CI, 67-83%]) with lower specificity (55% [95% CI, 53-61%]) and high negative predictive value (98% [95% CI, 97-98%]). Area under the receiver operator characteristic curve improved from 0.760 (95% CI, 0.716-0.804) for ECG alone to 0.798 (95% CI, 0.754-0.842) for the LVH risk score (P=0.0012), consistent with modest improvement in overall discrimination. Better screening for LVH may be achieved by combining simple tests, which collectively provide additional information compared with ECG alone. Further studies are needed to evaluate the impact and cost-effectiveness of a multimarker screening strategy.

BackgroundObesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear.ObjectivesThis study sought to determine the relationship between adipose tissue distribution and incident hypertension.MethodsNormotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI).ResultsAmong 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m2), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase).ConclusionsIncreased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association.

ObjectivesThe purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).BackgroundHigher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.MethodsWe followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.ResultsDifferences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.ConclusionsA single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors.

Low high density lipoprotein cholesterol (HDL-C) characterizes an atherogenic dyslipidemia that reflects adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Low HDL-C is also associated with increased risk of inflammatory disorders, malignancy, diabetes, and other diseases. This epidemiologic evidence has not translated to raising HDL-C as a viable therapeutic target, partly because HDL-C does not reflect HDL function. Mendelian randomization analyses that have found no evidence of a causal relationship between HDL-C levels and cardiovascular risk have decreased interest in increasing HDL-C levels as a therapeutic target even further. HDLs comprise distinct subpopulations of particles of varying size, charge and composition that have several dynamic and context-dependent functions, especially with respect to acute and chronic inflammatory states. These functions include reverse cholesterol transport, inhibition of inflammation and oxidation, and anti-diabetic properties. HDLs can be anti-inflammatory, which may protect against atherosclerosis and diabetes, as well as pro-inflammatory, which may help clear pathogens in sepsis. In addition, the molecular regulation of HDLs is complex, as evidenced by their association with multiple proteins, as well as bioactive lipids and non-coding RNAs. Clinical investigations of HDL biomarkers (HDL-C, HDL particle number, and apolipoprotein A-I) have revealed non-linear relationships with cardiovascular outcomes, differential relationships by sex and ethnicity, and differential patterns with coronary versus non-coronary events. Novel HDL markers may also have relevance for heart failure, cancer, and diabetes. HDL function markers, namely cholesterol efflux capacity, are associated with coronary disease, but remain research tools thus far. Ultimately, therapeutics that manipulate aspects of HDL metabolism remain the holy grail. None thus far have proven to be successful, but most have targeted HDL-C, not metrics of HDL function. Future therapeutic strategies should focus on optimizing HDL function in the right patients at the optimal time in their disease course. We provide here a framework to help the research and clinical communities, as well as funding agencies and stakeholders, obtain insights into current thinking on these topics, and what we predict will be an exciting future for research and development on HDLs.