Background:Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives:The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods:A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results:VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions:VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Purpose of Review Tricuspid regurgitation is a commonly encountered valvular pathology in patients with trans-tricuspid pacing or implantable cardioverter-defibrillator leads. Transcatheter tricuspid valve interventions are increasingly performed in patients at high surgical risk. Implantation of these valves can lead to the “jailing” of a trans-tricuspid lead. This practice carries both short- and long-term risks of lead failure and subsequent infection without the ability to perform traditional transvenous lead extraction. Herein, this manuscript reviews available therapeutic options for lead management in patients undergoing transcatheter tricuspid valve interventions. Recent Findings The decision to jail a lead may be appropriate in certain high-risk cases, though extraction may be a better option in most cases given the variety of options for re-implant, including leadless pacemakers, valve-sparing systems, epicardial leads, leads placed directly through prosthetic valves, and the completely subcutaneous implantable-defibrillator. Summary A growing number of patients meet the requirement for CIED implantation in the United States. A significant proportion of these patients will have tricuspid valve dysfunction, either related to or independent of their transvenous lead. As with any percutaneous intervention that has shown efficacy, the role of TTVI is also likely to increase as this therapy advances beyond the investigational phase. As such, the role of the heart team in the management of these patients will be increasingly critical in the years to come, and in those patients that have pre-existing CIED leads, we advocate for the involvement of an electrophysiologist in the heart team.

High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.

Background: Low quantities of circulating progenitor cells (CPCs), specifically CD34+ populations, reflect impairment of intrinsic regenerative capacity. This study investigates the relationship between subsets of CPCs and adverse outcomes.Methods: 1366 individuals undergoing angiography for evaluation of coronary artery disease (CAD) were enrolled into the Emory Cardiovascular Biobank. Flow cytometry identified CPCs as CD45med blood mono-nuclear cells expressing the CD34 epitope, with further enumeration of hematopoietic CPCs as CD133+/CXCR4+ cells and endothelial CPCs as vascular endothelial growth factor receptor-2 (VEGFR2+) cells. Adjusted Cox or Fine and Gray's sub-distribution hazard regression models analyzed the relationship between CPCs and 1) all-cause death and 2) a composite of cardiovascular death and non-fatal myocardial infarction (MI).Results: Over a median 3.1-year follow-up period (IQR 1.3-4.9), there were 221 (16.6%) all-cause deaths and 172 (12.9%) cardiovascular deaths/MIs. Hematopoietic CPCs were highly correlated, and the CD34+/CXCR4+ subset was the best independent predictor. Lower counts (<= median) of CD34+/CXCR4+ and CD34+/VEGFR2+ cells independently predicted all-cause mortality (HR 1.46 [95% CI 1.06-2.01], p = 0.02 and 1.59 [95% CI 1.15-2.18], p = 0.004) and cardiovascular death/MI (HR 1.50 [95% CI 1.04-2.17], p = 0.03 and 1.47 [95% CI 1.01-2.03], p = 0.04). A combination of low CD34+/CXCR4+ and CD34+/VEGFR2+ CPCs predicted all-cause death (HR 2.1, 95% CI 1.4-3.0; p = 0.0002) and cardiovascular death/MI (HR 2.0, 95% CI 1.3-3.2; p = 0.002) compared to those with both lineages above the cut-offs. Conclusions: Lower levels of hematopoietic and endothelial CPCs indicate diminished endogenous regenerative capacity and independently correlate with greater mortality and cardiovascular risk in patients with CAD.

Despite guideline-based therapy, patients with coronary artery disease (CAD) are at widely variable risk for cardiovascular events. This variability demands a more individu- alized risk assessment. Herein, we evaluate the prognostic value of 6 biomarkers: high-sen- sitivity C-reactive protein, heat shock protein-70, fibrin degradation products, soluble urokinase plasminogen activator receptor, high-sensitivity troponin I, and B-type natri- uretic peptide. We then develop a multi-biomarker-based cardiovascular event prediction model for patients with stable CAD. In total, 3,115 subjects with stable CAD who under- went cardiac catheterization at Emory (mean age 62.8 years, 17% Black, 35% female, 57% obstructive CAD, 31% diabetes mellitus) were randomized into a training cohort to identify biomarker cutoff values and a validation cohort for prediction assessment. Main outcomes included (1) all-cause death and (2) a composite of cardiovascular death and nonfatal myocardial infarction (MI) within 5 years. Elevation of each biomarker level was associated with higher event rates in the training cohort. A biomarker risk score was cre- ated using optimal cutoffs, ranging from 0 to 6 for each biomarker exceeding its cutoff. In the validation cohort, each unit increase in the biomarker risk score was independently associated with all-cause death (hazard ratio 1.62, 95% confidence interval [CI] 1.45 to 1.80) and cardiovascular death/MI (hazard ratio 1.52, 95% CI 1.35 to 1.71). A biomarker risk prediction model for cardiovascular death/MI improved the c-statistic (& UDelta; 6.4%, 95% CI 3.9 to 8.8) and net reclassification index by 31.1% (95% CI 24 to 37), compared with clinical risk factors alone. Integrating multiple biomarkers with clinical variables refines cardiovascular risk assessment in patients with CAD.& COPY; 2023 The Authors. Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) (Am J Cardiol 2023;203:315-324)

Background: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. Methods: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45 med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). Results: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors ( p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions ( p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts ( p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. Conclusion: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.

Previous studies have shown reduced cardiovascular risk with increasing high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high concentrations of HDL-C. Thus, we aimed to study the gender-specific relation between very high HDL-C levels (>80, >100 mg/100 ml) and adverse cardiovascular outcomes and the genetic basis in the general population enrolled in the United Kingdom Biobank. A total of 415,416 participants enrolled in the United Kingdom Biobank without coronary artery disease were included in this prospective cohort study, with a median follow-up of 9 years. A high HDL-C level >80 mg/100 ml was associated with increased risk of all-cause death (Hazard ratio [HR] 1.11, confidence interval [CI] 1.03 to 1.20, p = 0.005) and cardiovascular death (HR 1.24, CI 1.05 to 1.46, p = 0.01) after adjustment for age, gender, race, body mass index, hypertension, smoking, triglycerides, LDL-C, stroke history, heart attack history, diabetes, eGFR, and frequent alcohol use (defined as ≥3 times/week) using Cox proportional hazard and Fine and Gray's subdistribution hazard models, respectively. In gender-stratified analyses, such associations were only observed in men (all-cause death HR 1.79, CI 1.59 to 2.02, p <0.0001; cardiovascular death HR 1.92, CI 1.52 to 2.42, p <0.0001), but not in women (all-cause death HR 0.97, CI 0.88 to 1.06, p = 0.50; cardiovascular death HR 1.04, CI 0.83 to 1.31, p = 0.70). The findings persisted after adjusting for the genetic risk score comprised of known HDL-C-associated single nucleotide polymorphisms. Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease.

Importance:Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations. Objective:To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes. Design, Setting, and Participants:This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021. Exposure:High HDL-C levels (>80 mg/dL). Main Outcomes and Measures:The primary outcome was all-cause death. The secondary outcome was cardiovascular death. Results:A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23). Conclusions and Relevance:Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.

The relationship between restless legs syndrome (RLS) and cardiovascular disease remains enigmatic in the general population, and its prognostic value in patients with coronary artery disease (CAD) is unknown. In this study, the frequency of RLS-like symptoms was assessed using a validated instrument in 3,266 patients undergoing cardiac catheterization (mean age 64 years, 62% male, 23% Black, and 74% with obstructive CAD). Patients were followed for primary end points of cardiovascular death or incident myocardial infarction. Fine and Gray hazard models explored the association between RLS and incident events after adjustment for demographic and clinical risk factors. In the total cohort, 29% of patients reported mild (rare or sometimes) symptoms, and 15% of patients had moderate/severe (often to almost always) symptoms of RLS. Female sex (odds ratio [OR] 2.11, 95% confidence interval (CI), 1.68 to 2.57), body mass index (OR 1.12 per 5 kg/m(2) , 95% CI, 1.04 to 1.22), diabetes (OR 1.43, 95%,1.15 to 1.79), and beta-blocker use (OR 1.35, 95% CI, 1.07 to 1.72) were independently associated with moderate/severe symptoms of RLS compared with no symptoms. Over a 5-year followup period, 991 patients suffered an adverse event. Compared with those with no symptoms, patients with moderate/severe RLS had significantly higher risk of the primary end point (hazard ratio [HR] = 1.33, 95%),CI 1.01 to 1.76) after adjustment for demographic and clinical risk factors. The association was more significant in men than women, HR 1.98, 95% CI, 1.41 to 2.78 versus HR 0.99 (,95% CI, 0.64 to 1.52, p interaction= 0.013. In conclusion, among men with CAD, moderate-to-severe symptoms of RLS are associated with significantly higher risk of adverse cardiovascular outcomes, independent of traditional risk factors. (C) 2021 Elsevier Inc. All rights reserved.

The metabolic syndrome (MetS) is a constellation of comorbid derangements that increase the risk for both type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Diabetes may be preventable in many individuals with the MetS through the implementation of lifestyle and behavioral preventive strategies including dietary approaches. Several dietary patterns demonstrate efficacy in those living with the MetS to prevent progression to diabetes and reduce the risk of CVD. In this chapter, we review the Mediterranean dietary approach, plant-based diet, dietary approaches to stop hypertension (DASH), and intermittent fasting (IF) focusing on their impact on the MetS and the prevention of DM.

Before the coronavirus disease 2019 (COVID-19) pandemic, use of telehealth services had been limited in cardiovascular care. Potential benefits of telehealth include improved access to care, more efficient care management, reduced costs, the ability to assess patients within their homes while involving key caretakers in medical decisions, maintaining social distance, and increased patient satisfaction. Challenges include changes in payment models, issues with data security and privacy, potential depersonalization of the patient-clinician relationship, limitations in the use of digital health technologies, and the potential impact on disparities, including socioeconomic, gender, and age-related issues and access to technology and broadband. Implementation and expansion of telehealth from a policy and reimbursement practice standpoint are filled with difficult decisions, yet addressing these are critical to the future of health care.

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (<30 mg/dL) LDL-C. Cardiovascular event reduction increases log linearly in association with lowering LDL-C, without reaching any clear plateau even when very low LDL-C levels are achieved. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly haemorrhagic stroke) and long-term data are needed to address safety concerns. This review presents the familial conditions characterized by very low LDL-C, analyses trials with lipid-lowering agents where patients attained very low LDL-C, and summarizes the benefits and potential adverse effects associated with achieving very low LDL-C. Given the potential for cardiovascular benefit and short-term safe profile of very low LDL-C, it may be advantageous to attain such low levels in specific high-risk populations. Further studies are needed to compare the net clinical benefit of non-LDL-C-lowering interventions with very low LDL-C approaches, in addition to comparing the efficacy and safety of very low LDL-C levels vs. current recommended targets.

Objective: The underlying pathobiology of the paradoxical relationship between obesity and adverse outcomes in coronary artery disease (CAD) is unclear. Our objective was to determine the association between obesity and circulating progenitor cell (CPC) counts-a measure of intrinsic regenerative capacity-in asymptomatic individuals and patients with CAD and its impact on the obesity paradox. Approach and Results: CPCs were enumerated by flow cytometry as CD45(med+) cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 years of age; 28% obese) and 1277 patients with CAD (66 years of age; 39% obese). The association between obesity and CPCs was analyzed using linear regression models. The association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-year follow-up in patients with CAD was studied using Cox models. Obesity was independently associated with 16% to 34% higher CPC counts (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated by systemic inflammation, insulin resistance, or secretion but partly attenuated by cardiorespiratory fitness and body composition. In patients with CAD, obesity was associated with 8% to 12% higher CPC counts and 30% lower risk of adverse outcomes. Compared with nonobese patients, only obese patients with high CPC counts (CD34+ cells >= median, 1806 cells/mL) were at a lower risk (hazard ratio, 0.52 [95% CI, 0.31-0.88]), whereas those with low counts (<median) were at a similar risk (hazard ratio, 0.75 [95% CI, 0.48-1.15]). Conclusions: Obesity is associated with higher CPC counts. The obesity paradox of improved outcomes with obesity in CAD is limited to patients with intact regenerative capacity who have high CPC counts.

The national burden of cardiovascular disease (CVD) continues to impose significant risk of morbidity, mortality and increased costs. While traditional risk factors have been well-established, the evolving role of non-traditional risk factors, including socioeconomic and psychosocial factors, is increasingly being recognized. Several studies have acknowledged an association between marital status and the presence of CVD and its associated adverse outcomes. Across multiple U.S. and international cohorts, patients who are unmarried, including those who are divorced, separated, widowed, or never married, have an increased rate of adverse cardiovascular events when compared to their married counterparts. Some studies suggest that marriage may have a more protective role for men compared to women. Furthermore, dissatisfaction in a marriage and marriage quality have significant impact on cardiovascular risk. Psychosocial and socioeconomic factors, as well as other acute stressors, may contribute to the association between marital status and CVD outcomes, but the underlying mechanisms are not completely clear. Further investigation is required to identify potential targets for intervention and to determine whether more aggressive targeting of standard anti-atherosclerotic therapies can favorably impact CVD risk in unmarried patients. (c) 2019TheAuthors. PublishedbyElsevierInc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Despite unprecedented advances in treatment of atherosclerotic cardiovascular disease, it remains the leading cause of death and disability worldwide. Treatment of major traditional risk factors, including low-density lipoprotein-cholesterol, serves as the foundation of atherosclerotic risk reduction. However, there remains a significant residual risk of cardiovascular events despite optimal risk factor management. Beyond traditional risk factors, other drivers of residual risk have come to the forefront, including inflammatory, pro-thrombotic, and metabolic pathways that contribute to recurrent events and are often unrecognized and not addressed in clinical practice. This review will explore the evidence linking these pathways to atherosclerotic cardiovascular disease and potential future therapeutic options to attenuate residual cardiovascular risk conferred by these pathways.

The coronavirus disease 2019 (COVID-19) pandemic has upended global economies and brought about unprecedented challenges to healthcare systems. As of 5 May 2020, there have been over 3.5 million individuals globally with confirmed infection, including nearly 1.2 million confirmed in the USA and over 240 000 deaths globally including over 60 000 deaths in the USA [1]. Many of these fatalities have been in individuals with serious underlying medical conditions, namely diabetes, obesity, and cardiovascular disease. Those at higher risk for cardiovascular disease due to an ongoing independent global epidemic of obesity and diabetes likewise are those most vulnerable to increased morbidity and mortality from COVID-19. The observed case fatality rate in those with underlying cardiac conditions has been reported at 10%, nearly five-fold higher than observed rates in the general population [2]. Currently, the world population is in the midst of the worst of the COVID-19 pandemic, where life-saving measures including sheltering-in-place and social distancing are required to avoid overwhelming healthcare services needed for those experiencing the most serious manifestations of the illness. If these interventions are employed appropriately, many cities in the USA will eventually be past their peak incidence of disease. Yet, what will remain is a country with 30 million citizens living with diabetes, 84 million with pre-diabetes, at least 75 million with hypertension, and a prevalence of obesity of nearly 40% [3,4]. These individuals are at high risk for not only cardiovascular events, but as we have learned, also for adverse consequences related to potential future infectious diseases that may threaten the population. The lessons learned during the recovery will be critical to ensure the health of the population going forward. Early reports from China have been fundamental to detail the prevalence of cardiovascular and cardiometabolic risk factors among infected individuals and instrumental in shaping our understanding of the spectrum of risk related to COVID-19. In a cohort of 1099 patients from mainland China, the overall prevalence of diabetes was 7%, though the prevalence in those with severe illness increased to 16%, and further increased to 27% for those who met the composite endpoint of mechanical ventilation or death [5]. The overall prevalence of hypertension was 15%. In those with severe illness, the prevalence increased to 24%, and in those who reached the composite endpoint of death or mechanical ventilation, the prevalence was 35%. Coronary heart disease was seen in 2.5, 6, and 9% in the overall cohort, those with severe illness, and those who reached the composite endpoint, respectively. From this, an understanding has developed that the age of individuals, in addition to those living with underlying chronic health conditions are most likely to suffer worse outcomes from this acute infectious illness. In the USA, similar trends have been observed. In 7162 patients for whom data were available, the Centers for Disease Control and Prevention reported the percentage of patients with COVID-19 with at least one underlying health condition or risk factor was higher among those requiring ICU admission (78%) and those requiring hospitalization without ICU admission (71%) than among those who were not hospitalized (27%) [6]. Diabetes was present in 6% of those not requiring hospitalization, as compared to 24% who were hospitalized and 32% of those requiring ICU admission. Similarly, cardiovascular disease was noted in 5% of those not requiring hospitalization, 23% of those requiring hospital admission, and 29% of those requiring ICU admission. Hypertension and obesity were the most common underlying comorbidities in patients requiring hospitalization at 50 and 48%, respectively. In 5700 inpatients from the New York City area, the current epicenter of the pandemic, the prevalence of hypertension, diabetes, obesity, and coronary artery disease was notably higher than reported in Chinese cohorts, with prevalence of 56, 34, 42, and 11% in those patients requiring hospitalization [7]. Again, those with a higher burden of risk factors fared poorly. Among COVID-19 positive inpatients in New York City, obese individuals under 60 years of age were twice as likely to require admission to the hospital as their nonobese counterparts [8]. This finding has been replicated in the UK, where an apparent dose-response association with increasing adiposity and poor glycemic control has been observed [9]. There are a number of potential explanations for these observations, including advanced age in those with more comorbidities, impaired immunity due to diabetes and obesity, higher ACE2 expression in hypertensive individuals, increased inflammation and vascular endothelial dysfunction, though exact mechanisms for adverse outcomes in these groups are still incompletely understood and likely multifactorial. What is strikingly consistent is that across populations, the presence of risk factors for cardiovascular disease portend a worse prognosis in those infected with COVID-19. People with obesity often have higher levels of adipokine-related inflammation predisposing their immune systems to overreact to coronavirus infection. In addition, more abundant central adiposity creates restrictive pulmonary physiology adding to respiratory compromise in such patients [10]. There is a great need to understand the potential impact that the management of cardiovascular risk factors may have on outcomes in patients with COVID-19. While there was initial concern whether treatment of hypertension with angiotensin converting enzyme (ACE)-inhibitors or angiotensin receptor blockers might increase susceptibility to infection with COVID-19 due to their effects on increasing ACE2 expression, leading to calls by some to withdraw patients from such therapies, a recent investigation [11] of nearly 9000 patients across 169 hospitals across Asia, Europe, and North America showed no increase in the risk of in-hospital death from the use of angiotensin II receptor blockers and a possible reduced risk of death from use of ACE-inhibitors (odds ratio 0.33; 95% confidence interval, 0.20–0.54). Importantly, this study was notable for significantly increased odds of death in those with pre-existing coronary artery disease, heart failure, arrhythmias, in addition to chronic obstructive pulmonary disease, emphasizing the potential importance of both the prevention and management of these conditions in the COVID-19 era. While no benefit was found from either antiplatelet or statin use, clinical trials are needed to further evaluate the impact cardioprotective therapies have on outcomes in patients with COVID-19. The possible role statins may have in such infections has been raised, due to prior evidence, they may improve outcomes in persons with influenza, including those on ventilators from pneumonia [12]. As the virus has spread throughout the USA, the disturbing and familiar association of racial and socioeconomic disparities that have been observed in poorer outcomes related to cardiovascular disease also appears to be true in COVID-19. Among states that have released data regarding race, African-Americans have accounted for 34% of total COVID-19 deaths, despite making up only 13% of the population in those states [13]. In New York City, African-Americans made up 28% of the fatalities, despite being 22% of the population, and Hispanics made up 34% of fatalities, despite being 29% of the population [14]. By comparison, whites (32% of the city’s population) make up 27% of the fatalities, and Asians (14% of the population) represent 7% of the fatalities. This trend is occurring throughout the USA. The reasons for this are numerous and embedded in widening gaps in health among disadvantaged populations resulting in a higher burden of risk factors, particularly diabetes, obesity, and hypertension, as well as poorer access to care. Addressing social determinants of health as well as improving the management of these and other cardiovascular risk factors in these priority populations will hopefully have a beneficial impact in the event of future waves of COVID-19 or other such pandemics. The impact of this invisible pathogen highlights the importance of social determinants of health that we know place minorities and the poor at a significant disadvantage when it comes to health and lifespan. The question of accepting these deeply entrenched disparities as an inevitability or as ethically unacceptable is one of the most pressing questions to be answered in the post-COVID-19 USA. Cardiovascular and cardiometabolic prevention must be a high-level priority in the post-pandemic recovery phase and the era of COVID-19. The need for significant investment by governmental and healthcare sectors in programs designed to address health promotion and chronic disease prevention is essential. Critical now in the active stage of the pandemic is active intervention including testing, along with active protection of vulnerable groups. The most effective approach to achieving this is likely to involve a mix of targeted testing, earlier case detection, isolation, and segregation within the care environment. These factors are what seem to separate effective pandemic management from less effective management. Going forward, improved prevention and management of cardiovascular disease and cardiometabolic comorbidities will hopefully lead to better outcomes in the recovery phase of the current pandemic and future such confrontations. Eventually, COVID-19-related cases and fatalities will diminish, governments will determine societies are ready to reopen to minimize damage to world economies while balancing the containment of the current pandemic and minimizing future infection waves, and everyday life will begin to be more recognizable. Vaccine trials are underway which will hopefully lead to immunity from this virus in the coming years. However, one of the many lessons to be learned from this global pandemic is that a chronically unhealthy population will be ill-equipped to handle the next such challenge. Acknowledgements D.S.D. is supported by the Abraham J. & Phyllis Katz Foundation. Conflicts of interest There are no conflicts of interest.