Homozygosity for a premature stop codon (X) in the ACTN3 “sprinter” gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.

The Healthy People Initiative has served as the leading disease prevention and health promotion roadmap for the nation since its inception in 1979. Healthy People 2020 (HP2020), the initiative’s current iteration, sets a national prevention agenda with health goals and objectives by identifying nationwide health improvement priorities and providing measurable objectives and targets from 2010 to 2020. Central to the overall mission and vision of Healthy People is an emphasis on achieving health equity, eliminating health disparities, and improving health for all population groups. The Heart Disease and Stroke (HDS) Work Group of the HP2020 Initiative aims to leverage advances in biomedical science and prevention research to improve cardiovascular health across the nation. The initiative provides a platform to foster partnerships and empower professional societies and nongovernmental organizations, governments at the local, state, and national levels, and healthcare professionals to strengthen policies and improve practices related to cardiovascular health. Disparities in cardiovascular disease burden are well recognized across, for example, race/ethnicity, sex, age, and geographic region, and improvements in cardiovascular health for the entire population are only possible if such disparities are addressed through efforts that target individuals, communities, and clinical and public health systems. This article summarizes criteria for creating and tracking the 50 HDS HP2020 objectives in 3 areas (prevention, morbidity/mortality, and systems of care), reports on progress toward the 2020 targets for these objectives based on the most recent data available, and showcases examples of relevant programs led by participating agencies. Although most of the measurable objectives have reached the 2020 targets ahead of time (n=14) or are on track to meet the targets (n=7), others may not achieve the decade’s targets if the current trends continue, with 3 objectives moving away from the targets. This summary illustrates the utility of HP2020 in tracking measures of cardiovascular health that are of interest to federal agencies and policymakers, professional societies, and other nongovernmental organizations. With planning for Healthy People 2030 well underway, stakeholders such as healthcare professionals can embrace collaborative opportunities to leverage existing progress and emphasize areas for improvement to maximize the Healthy People initiative’s positive impact on population-level health.

Cardiovascular diseases remain the leading cause of mortality and a major contributor to preventable deaths worldwide. The dominant modifiable risk factors and the social and environmental determinants that increase cardiovascular risk are known, and collectively, are as important in racial and ethnic minority populations as they are in majority populations. Their prevention and treatment remain the foundation for cardiovascular health promotion and disease prevention. Genetic and epigenetic factors are increasingly recognized as important contributors to cardiovascular risk and provide an opportunity for advancing precision cardiovascular medicine. In this review, we explore emerging concepts at the interface of precision medicine and cardiovascular disease in racial and ethnic minority populations. Important among these are the lack of racial and ethnic diversity in genomics studies and biorepositories; the resulting misclassification of benign variants as pathogenic in minorities; and the importance of ensuring ancestry-matched controls in variant interpretation. We address the relevance of epigenetics, pharmacogenomics, genetic testing and counseling, and their social and cultural implications. We also examine the potential impact of precision medicine on racial and ethnic disparities. The National Institutes of Health’s All of Us Research Program and the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine Initiative are presented as examples of research programs at the forefront of precision medicine and diversity to explore research implications in minorities. We conclude with an overview of implementation research challenges in precision medicine and the ethical implications in minority populations. Successful implementation of precision medicine in cardiovascular disease in minority populations will benefit from strategies that directly address diversity and inclusion in genomics research and go beyond race and ethnicity to explore ancestry-matched controls, as well as geographic, cultural, social, and environmental determinants of health.