Introduction to the Compendium on Early Cardiovascular Disease.

Abstract

HomeCirculation ResearchVol. 132, No. 12Introduction to the Compendium on Early Cardiovascular Disease Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBIntroduction to the Compendium on Early Cardiovascular Disease Matthew Nayor, Donald M. Lloyd-Jones and Ravi V. Shah Matthew NayorMatthew Nayor https://orcid.org/0000-0002-6993-9396 Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, MA. Department of Preventive Medicine, Division of Cardiology, Department of Medicine, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL. Vanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author , Donald M. Lloyd-JonesDonald M. Lloyd-Jones Correspondence to: Donald Lloyd-Jones, MD, Department of Preventive Medicine Northwestern Feinberg School of Medicine 680 N Lake Shore Dr., Suite 1400 Chicago, IL 60611. Email: E-mail Address: [email protected] https://orcid.org/0000-0003-0847-6110 Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, MA. Department of Preventive Medicine, Division of Cardiology, Department of Medicine, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL. Vanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author and Ravi V. ShahRavi V. Shah https://orcid.org/0000-0002-4471-7156 Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, MA. Department of Preventive Medicine, Division of Cardiology, Department of Medicine, and Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL. Vanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author Originally published8 Jun 2023https://doi.org/10.1161/CIRCRESAHA.123.323095Circulation Research. 2023;132:1567–1569Since initial findings from the Framingham Heart Study were published in the early 1960s, the field of cardiovascular prevention has been captivated by the search for causal risk factors responsible for cardiovascular disease (CVD). Seminal work by Dawber, Kannel, and colleagues to define the canonical CVD risk factors of hypertension, smoking, and dyslipidemia in Framingham, Massachusetts, are now foundational for cardiovascular prevention efforts worldwide.1 These observations, and many others along the way, have led to the development of tools for CVD risk assessment, informed lifestyle and behavioral approaches to reduce risk factor burden, and driven drug discovery, culminating in tremendous advancements in CVD prevention and treatment. However, in the United States, the progress in reducing CVD mortality enjoyed over the previous half century has stagnated in recent years,2 and we will be unable to curtail the epidemic of CVD, much less conquer it, solely through available means on tertiary, secondary, and primary prevention. Persistent disparities in detection, surveillance, and therapy across geographic, socioeconomic, and racial-ethnic groups also contribute to disparities in CVD prevention and treatment, likely contributing to the observed plateau in CVD mortality. Compounding these social-environmental features is a shift in cardiometabolic risk profiles accompanied by a dramatic rise in obesity and diabetes, with >70% of US adults currently characterized as overweight or obese.2 Data from national surveys and cohort studies have documented an alarming rise in obesity in adolescence and early adulthood, which has profound long-term consequences for CVD risk over the life course.2,3 These observations have motivated attempts to address risk factors earlier in their development by key patient advocates and funders, with the American Heart Association4 and National Heart, Lung, and Blood Institutes5 investing in efforts to study methods for preventing CVD earlier in its course to bend the curve of CVD mortality.Several lines of evidence support the importance of earlier application of preventive measures to reduce individual and population CVD burden and reduce disparity. One strategy, endorsed by the American Heart Association, is a reorientation of CVD prevention around a more positive cardiovascular health (CVH) promotion construct. Current evidence suggests that favorable levels of CVH diminish steadily across early to mid-life, with a prevalence of ≈50% with high CVH at 10 years old that falls to ≈10% by age 50.6 The long-term favorable implications of high early and mid-life CVH on long-term CVD events, overall longevity, healthy longevity, and compression of morbidity, have been well documented,7,8 Indeed, individuals who reach mid-life with optimal risk factor levels experience very low lifetime risks for major CVD events (≈5%–8%) relative to 70% for individuals with greater than 2 risk factors.9 In other words, in the absence of the traditional risk factors, CVD becomes an uncommon disease, and there are beneficial effects on many other chronic diseases of aging as well.8 Furthermore, treatment to achieve optimal risk levels (primary prevention) is different from, and less effective than, prevention of risk factor development in the first place (primordial prevention).10,11 There is a price to be paid for spending time with elevated lipid, blood pressure, and blood glucose levels, even within levels thought to be clinically normal; cumulative exposure to these risk factors across early life drive early and later life events because of the lifelong time course of CVD development.12Disparities in CVD outcomes have their roots in earlier exposure to CVD risk factors and Black individuals have the lowest CVH scores across different racial-ethnic groups in the United States.13 Thankfully, loss of ideal CVH by mid-life is not predetermined: young adults with a healthy lifestyle have a 60% probability of maintaining optimal CVH later in life, compared with 2% for individuals with low CVH in early life.14 In addition, serial counseling on CVD risk in the first and second decade of life results in higher CVH scores in late adolescence.15How then can we reconcile these current trends in CVH and CVD mortality with recent scientific progress in assessing, targeting, and modulating CVD risk early in its pathogenesis?This Compendium issue of Circulation Research aims to begin to address this question by focusing on rapidly evolving areas in early CVD prevention and health promotion, with an eye toward state-of-the-art methods to characterize and influence CVD risk. The first set of contributions focus on phenotyping the early CVD state. Pedamallu et al16 set the stage by discussing evidence of CVH trajectories from early life, which track into mid-life, highlighting opportunities to promote CVH in children and young adults. These approaches are complemented by Khan et al,17 who introduce the concept of pregnancy as a lens into future CVH, issuing a clarion call for a more proactive approach to assessing, monitoring, and modifying CVH throughout pregnancy to affect long-term CVD risk. CVH during the prepregnancy period in young adulthood and gestational CVH also seem to have important implications for pregnancy outcomes, offspring health and intergenerational transmission of CVH and CVD risk. Varadarajan et al’s18 comments on imaging and subclinical CVD—a major area of modern cardiovascular epidemiology targeting early structural-functional phenotypes that presage clinical CVD—remind us of the opportunity for detecting individuals on the fast track for subclinical, and thus clinical, CVD development.The second segment of the Compendium illustrates the importance of molecular genetics and omic technologies to elucidate risk. The contributions of Li et al19 and Ordovas and Baccarelli20 provide a state-of-the-art perspective on how genomic and epigenetic information—potentially useful before clinical risk factors are manifest—might be leveraged to inform approaches for CVD prevention throughout the life course, with a specific focus on early life. Tahir and Gerszten21 next summarize how high-throughput molecular assays capable of quantifying thousands of circulating molecules—part of the omic revolution in modern molecular science—have been successfully used to focus phenotyping and detection of early CVD risk (precision medicine). Gabriel and Ferguson22 finally illustrate the role of metagenomics in cardiometabolic health throughout life, providing a vision of how these data can be used to tailor intervention to reduce cardiometabolic risk in younger individuals.Even if we identify risk with increasing precision, questions remain regarding how to intervene to promote CVH, advance CVD prevention, and reduce the burden of CVD risk. The third segment of the Compendium features 4 articles aimed at modifiable behaviors and risk factors integral to promoting CVH. Brandt et al23 review the relationship of diet with CVH and discuss recent evidence regarding optimal dietary patterns for CVH. The authors importantly touch on the relevance of both food and nutritional insecurity in contributing to cardiometabolic disease and poor CVH, especially in younger individuals. Along similar lines, Zhang et al24 review data around the emerging concept of the exposome—an all-encompassing collection of internal and external features (eg, air pollution, built environment) that are thought to influence CVD—culminating in illustrations of how developing this information may led to multi-level interventions to promote healthier communities. Finally, Perry et al25 close out the Compendium with a focus on the role of physical activity in CVH throughout the life course, beginning with promoting healthy behaviors in childhood. The opportunities available for lifelong CVH promotion and CVD prevention in each of these areas, as well as those throughout the compendium, of course are driven by upstream factors including the critically important array of social determinants of health. The reviews in this Compendium series characterize and contextualize contemporary approaches to assess, measure, and intervene on CVH and CVD risk early in life. A common thread across these contributions is the importance of bringing inquiry into the interventional space, addressing how we can best translate investments in cardiovascular prevention science to individuals at highest risk during a vulnerable period early in life. We envision the Compendium as a starting point for these conversations to stimulate reflection and creativity around these critical problems, ultimately shifting the paradigm of prevention away from short-term risk to long-term CVH promotion in line with the vision of an endgame to CVD.26Article InformatonDisclosures None.FootnotesFor Disclosures, see page 1568.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: Donald Lloyd-Jones, MD, Department of Preventive Medicine Northwestern Feinberg School of Medicine 680 N Lake Shore Dr., Suite 1400 Chicago, IL 60611. Email: [email protected]edu