Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

AIMS: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. METHODS AND RESULTS: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). CONCLUSION: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Higher levels of small dense particles of LDL cholesterol, better known as the 'bad cholesterol', are associated with a greater risk for the presence of coronary artery calcium, a strong marker for heart disease, even when accounting for estimated total (small dense + large body particles) LDL cholesterol.This risk is stronger in older individuals.Peak risk seems to occur between 49 and 71 mg/dL and does not increase further at higher levels.

2023 update: The importance of cardiorespiratory fitness in the United States.

The American Heart Association issued a Policy Statement in 2013 that characterized the importance of cardiorespiratory fitness (CRF) as an essential marker of health outcomes and specifically the need for increased assessment of CRF. This statement summarized the evidence demonstrating that CRF is "one of the most important correlates of overall health status and a potent predictor of an individual's future risk of cardiovascular disease." Subsequently, this Policy Statement led to the development of a National Registry for CRF (Fitness Registry and the Importance of Exercise: A National Data Base [FRIEND]) which established normative reference values for CRF for adults in the United States (US). This review provides an overview of the progress made in the past decade to further our understanding of the importance of CRF, specifically related to prevention and for clinical populations. Additionally, this review overviews the evolvement and additional uses of FRIEND and summarizes a hierarchy of assessment methods for CRF. In summary, continued efforts are needed to expand the representation of data from across the US, and to include data from pediatric populations, to further develop the CRF Reference Standards for the US as well as further develop Global CRF Reference Standards.

How to interpret a cardiorespiratory fitness assessment - Key measures that provide the best picture of health, disease status and prognosis.

Graded exercise testing is a widely accepted tool for revealing cardiac ischemia and/or arrhythmias in clinical settings. Cardiopulmonary exercise testing (CPET) measures expired gases during a graded exercise test making it a versatile tool that helps reveal underlying physiologic abnormalities that are in many cases only present with exertion. It also characterizes one's health status and clinical trajectory, informs the therapeutic plan, evaluates the efficacy of therapy, and provides submaximal and maximal information that can be used to tailor an exercise intervention. Practitioners can also modify the mode and protocol to allow individuals of all ages, fitness levels, and most disease states to perform a CPET. When used to its full potential, CPET can be a key tool used to optimize care in primary and secondary prevention settings.

Rest-Activity Rhythms Are Associated With Prevalent Cardiovascular Disease, Hypertension, Obesity, and Central Adiposity in a Nationally Representative Sample of US Adults.

BACKGROUND: Rest-activity rhythms (RARs), a measure of circadian rhythmicity in the free-living setting, are related to mortality risk, but evidence is limited on associations with cardiovascular disease (CVD) and its risk factors. METHODS AND RESULTS: Participants included 4521 adults from the 2013 to 2014 National Health and Nutrition Examination Survey physical activity monitoring examination. Wrist-worn ActiGraph GT3X+ data were used to estimate RARs. Multivariable logistic models evaluated associations of RARs with prevalent CVD, hypertension, obesity, and central adiposity. Participants (mean age, 49 years) in the highest versus lowest tertile of relative amplitude (greater circadian rhythmicity) had 39% to 62% lower odds of prevalent CVD, hypertension, obesity, and central adiposity. A more active wake period was associated with 19% to 72% lower CVD, hypertension, obesity, and central adiposity odds. Higher interdaily stability (regular sleep-wake and rest-activity patterns) was related to 52% and 23% lower CVD and obesity odds, respectively. In contrast, participants in the highest versus lowest tertile of intradaily variability (fragmented RAR and inefficient sleep) had >3-fold and 24% higher CVD and obesity odds, respectively. A later and less restful sleep period was associated with 36% to 2-fold higher CVD, hypertension, obesity, and central adiposity odds. A statistically significant linear trend was observed for all associations (P-trend<0.05). CONCLUSIONS: A robust, stable, and less fragmented RAR, an active wake period, and an earlier and more restful sleep period are associated with lower prevalent CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The magnitude, timing, and regularity of sleep-wake and rest-activity patterns may be important targets for reducing cardiovascular risk.

Clinicians' self-reported efficacy in cardiovascular prevention practice in the southeastern United States.

Aim: We assessed self-reported efficacy in cardiovascular prevention practice among internal medicine, family medicine, endocrinology and cardiology clinicians. Patients & methods: We emailed a 21-item questionnaire to 956 physicians, nurse practitioners, physician assistants and pharmacists. Results: 264 clinicians responded (median age: 39 years, 55% women, 47.9% specialists). Most expressed high self-efficacy in lifestyle counselling, prescribing statins, metformin, and aspirin in primary prevention, but low self-efficacy in managing specialized conditions like elevated lipoprotein(a). Compared with specialists, PCPs expressed lower self-efficacy in managing advanced lipid disorders and higher self-efficacy in prescribing sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Conclusion: Self-efficacy in cardiovascular prevention varied across specialties. Future research should explore relevant provider, clinic and system level factors to optimize cardiovascular prevention.

Obesity management for cardiovascular disease prevention.

Background: Obesity is a complex disease that leads to higher morbidity and mortality and its rate in the United States is rapidly rising. Targeting obesity management is one of the cornerstones of preventive medicine. Early intervention can significantly reduce the risk of developing cardiovascular disease. While it is well known that lifestyle interventions such as healthful nutrition and routine physical activity are the first and most important step in management, some do not achieve the desired results and require further therapies. Methods: A literature review was conducted, that included clinical documents, public scientific citations and peer review articles to evaluate anti-obesity medications, endoscopic procedures and bariatric surgeries in the management of obesity. We also included effects of these interventions on weight loss, cardiovascular disease risk reduction and side effects. Results: This clinical review summarizes recent evidence for the different approaches in obesity management including medications, common endoscopic procedures and bariatric surgeries. For more detailed review on the different management options discussed, we recommend reviewing Obesity Medicine Association Clinical Practice Statement [1]. Conclusion: Management of obesity reduces cardiovascular risk, improves metabolic parameters and other important health outcomes. Different management approaches are available, hence, a high level of awareness of the growing epidemic of obesity is needed to ensure timely referrals to obesity medicine specialists.

Specialty preference for cardiovascular prevention practice in the Southeast US and role of a preventive cardiologist.

INTRODUCTION: Cardiovascular disease (CVD) prevention is practiced concurrently by providers from several specialties. Our goal was to understand providers' preference of specialties in CVD prevention practice and the role of preventive cardiologists. MATERIALS AND METHODS: Between 11 October 2021 and 1 March 2022, we surveyed providers from internal medicine, family medicine, endocrinology, and cardiology specialties to examine their preference of specialties in managing various domains of CVD prevention. We examined categorical variables using Chi square test and continuous variables using t or analysis of variance test. RESULTS: Of 956 invitees, 263 from 21 health systems and 9 states responded. Majority of respondents were women (54.5%), practicing physicians (72.5%), specializing in cardiology (43.6%), and working at academic centers (51.3%). Respondents favored all specialties to prescribe statins (43.2%), ezetimibe (37.8%), sodium-glucose cotransporter-2 (SGLT2) inhibitors (30.5%), and aspirin in primary prevention (36.3%). Only 7.9% and 9.5% selected cardiologists and preventive cardiologists, respectively, to prescribe SGLT2 inhibitors. Most preferred specialists (i.e. cardiology and endocrinology) to manage advanced lipid disorders, refractory hypertension, and premature coronary heart disease. The most common conditions selected for preventive cardiologists to manage were genetic lipid disorders (17%), cardiovascular risk assessment (15%), dyslipidemia (13%), and refractory/resistant hypertension (12%). CONCLUSIONS: For CVD prevention practice, providers favored all specialties to manage common conditions, specialists to manage complex conditions, and preventive cardiologists to manage advanced lipid disorders. Cardiologists were least preferred to prescribe SGLT2 inhibitor. Future research should explore reasons for selected CVD prevention practice preferences to optimize care coordination and for effective use of limited expertise.

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. OBJECTIVE: Characterize the relationship between SMI on ECG and CAC. METHODS: Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. RESULTS: Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). CONCLUSION: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

High density lipoprotein: When to rethink too much of a good thing.

High density lipoprotein cholesterol (HDL-C) is a known contributor to atherosclerotic cardiovascular disease (ASCVD) risk when HDL-C <40 mg/dL in men and <50 mg/dL in women. There has been much interest in the potential cardioprotective properties of HDL-C, as it removes cholesterol from the periphery to the liver for exertion and holds inherent anti-thrombotic and anti-inflammatory properties. However, clinical trials raising HDL-C pharmacologically have not shown to improve cardiovascular outcomes. In fact, observational studies have demonstrated an increased risk of non-cardiovascular mortality and infection when HDL-C >90 mg/dL and >70 mg/dL in women and men, respectively. The ability for the HDL particle to effectively transport cholesterol from the periphery for excretion in bile is more complex than illustrated on a standard cholesterol panel. There is variability in its function, size, density, subclass, reverse cholesterol transport, and cholesterol efflux capacity, which impact the particles ability to effectively reduce cardiovascular disease (CVD) risk. Research has shown that HDL particles are prone to have a reduction in its efficacy in response to infection, auto-immune disease, menopause and cardiometabolic conditions during pregnancy. Additionally, recent studies have shown that low HDL-C may not adequately influence ASCVD risk in Black adults. The purpose of this contemporary review is to highlight the utility of using HDL-C in assessing CVD risk.

Blood Pressure and Cardiovascular Disease Mortality Among US Adults: A Sex-Stratified Analysis, 1999-2019.

BACKGROUND: Most research examining the association between blood pressure (BP) and cardiovascular disease (CVD) is sex-agnostic. Our goal was to assess sex-specific associations between BP and CVD mortality. METHODS: We combined ten cycles of the National Health and Nutrition Examination Survey (1999-2018), N=53 289. Blood pressure was measured 3× and averaged. Data were linked to National Death Index data, and CVD mortality through December 31, 2019, was defined from International Classification of Diseases, Tenth Revision codes. We estimated sex-stratified, multivariable-adjusted incidence rate ratios (IRRs) for CVD mortality. RESULTS: Over a median follow-up of 9.5 years, there were 2405 CVD deaths. Associations between categories of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with CVD mortality differed by sex (P<0.01). Among men, compared with SBP of 100 to <110 mm Hg, CVD mortality was 76% higher with SBP ≥160 mm Hg (IRR, 1.76 [95% CI, 1.27-2.44]). Among women, compared with SBP 100 to < 110 mm Hg, CVD mortality was 61% higher with SBP 130 to 139 mm Hg (IRR, 1.61 [95% CI, 1.02-2.55]), 75% higher with SBP 140 to 159 mm Hg (IRR, 1.75 [95% CI, 1.09-2.80]), and 113% higher with SBP≥160 mm Hg (IRR, 2.13 [95% CI, 1.35-3.36]). Compared with DBP 70 to <80 mm Hg, CVD mortality was higher with DBP <70 mm Hg and DBP≥80 mm Hg among men, and higher with DBP <50 mm Hg and DBP≥80 mm Hg among women. CONCLUSIONS: The association between BP and CVD mortality differed by sex, with increased CVD mortality risk present at lower levels of systolic blood pressure among women compared with men.

Understanding the molecular mechanisms of statin pleiotropic effects.

Statins represent the cornerstone of pharmacotherapy for the prevention of atherosclerotic cardiovascular disease. These medications not only reduce low-density lipoprotein cholesterol (LDL-C) via inhibition of 3-hydroxy-3-methylglutarate attached to CoA reductase, the key rate-limiting step in the cholesterol biosynthetic pathway, but also upregulate expression of the low-density lipoprotein receptor, improving serum clearance. Given LDL-C is a causal risk factor for the development of atherosclerosis, these complementary mechanisms largely explain why statin therapy leads to reductions in major adverse cardiovascular events. However, decades of basic and clinical research have suggested that statins may exert other effects independent of LDL-C lowering, termed pleiotropic effects, which have become a topic of debate among the scientific community. While some literature suggests statins may improve plaque stability, reduce inflammation and thrombosis, decrease oxidative stress, and improve endothelial function and vascular tone, other studies have suggested potential harmful pleiotropic effects related to increased risk of muscle-related side effects, diabetes, hemorrhagic stroke, and cognitive decline. Furthermore, the introduction of newer, non-statin LDL-C lowering therapies, including ezetimibe, proprotein convertase subtilisin/Kexin Type 9, and bempedoic acid, have challenged the statin pleiotropy theory. This review aims to provide a historical background on the development of statins, explore the mechanistic underpinnings of statin pleiotropy, review the available literature, and provide up to date examples that suggest statins may exert effects outside of LDL-C lowering and the cardiovascular system.

Circulating ketone bodies and cardiovascular outcomes: the MESA study.

AIMS: Ketone bodies (KB) are an important alternative metabolic fuel source for the myocardium. Experimental and human investigations suggest that KB may have protective effects in patients with heart failure. This study aimed to examine the association between KB and cardiovascular outcomes and mortality in an ethnically diverse population free from cardiovascular disease (CVD). METHODS AND RESULTS: This analysis included 6796 participants (mean age 62 ± 10 years, 53% women) from the Multi-Ethnic Study of Atherosclerosis. Total KB was measured by nuclear magnetic resonance spectroscopy. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with cardiovascular outcomes. At a mean follow-up of 13.6 years, after adjusting for traditional CVD risk factors, increasing total KB was associated with a higher rate of hard CVD, defined as a composite of myocardial infarction, resuscitated cardiac arrest, stroke, and cardiovascular death, and all CVD (additionally included adjudicated angina) [hazard ratio, HR (95% confidence interval, CI): 1.54 (1.12-2.12) and 1.37 (1.04-1.80) per 10-fold increase in total KB, respectively]. Participants also experienced an 87% (95% CI: 1.17-2.97) increased rate of CVD mortality and an 81% (1.45-2.23) increased rate of all-cause mortality per 10-fold increase in total KB. Moreover, a higher rate of incident heart failure was observed with increasing total KB [1.68 (1.07-2.65), per 10-fold increase in total KB]. CONCLUSION: The study found that elevated endogenous KB in a healthy community-based population is associated with a higher rate of CVD and mortality. Ketone bodies could serve as a potential biomarker for cardiovascular risk assessment.

What has cardiac rehabilitation looked like in the COVID-19 pandemic: Lessons learned for the future.

The global coronavirus disease 2019 (COVID-19) pandemic prompted widespread national shutdown, halting or dramatically reducing the delivery of non-essential outpatient services including cardiac rehabilitation (CR). Center-based CR services were closed for as few as two weeks to greater than one year and the uncertainty surrounding the duration of the lockdown phase prompted programs to consider programmatic adaptations that would allow for the safe and effective delivery of CR services. Among the actions taken to accommodate in person CR sessions included increasing the distance between exercise equipment and/or limiting the number of patients per session. Legislative approval of reimbursing telehealth or virtual services presented an opportunity to reach patients that may otherwise have not considered attending CR during or even before the pandemic. Additionally, the considerable range of symptoms and infection severity as well as the risk of developing long lasting, debilitating symptoms has complicated exercise recommendations. Important lessons from publications reporting findings from clinical settings have helped shape the way in which exercise is applied, with much more left to discover. The overarching aim of this paper is to review how programs adapted to the COVID-19 pandemic and identify lessons learned that have positively influenced the future of CR delivery.

Defining preventive cardiology: A clinical practice statement from the American Society for Preventive Cardiology.

Remarkable transformations in science and healthcare have resulted in declines in mortality from cardiovascular disease over the past several decades, largely driven by progress in prevention and treatment of persons at risk. However, these trends are now beginning to stall, as our county faces increases in cardiovascular risk factors including overweight and obesity, type 2 diabetes mellitus, and metabolic syndrome. Furthermore, poor long-term adherence to a healthy lifestyle and lifesaving pharmacotherapy have exacerbated these trends, with recent data suggesting unprecedented increases in cardiovascular morbidity and mortality. A paradigm shift is needed to improve the cardiovascular health of our nation. Preventive cardiology, a growing subspecialty of cardiovascular medicine, is the practice of primordial, primary, and secondary prevention of all cardiovascular diseases. Preventive cardiologists and preventive cardiology specialists are well equipped with the knowledge and skill-set necessary to reduce deaths related to the growing burden of heart disease and its risk factors. Despite dedicated efforts, cardiovascular disease remains the leading killer of men and women in the United States. Although there is little debate regarding the importance of prevention, many healthcare professionals question the need for preventive cardiology as a distinct subspecialty. Additionally, the field's growth has been hampered by a lack of organization and standardization, and variability of training within programs across the country. The purpose of this document is to delineate the key attributes that define the field of preventive cardiology according to the American Society for Preventive Cardiology.

Ten things to know about ten cardiovascular disease risk factors - 2022.

The American Society for Preventive Cardiology (ASPC) "Ten things to know about ten cardiovascular disease risk factors - 2022" is a summary document regarding cardiovascular disease (CVD) risk factors. This 2022 update provides summary tables of ten things to know about 10 CVD risk factors and builds upon the foundation of prior annual versions of "Ten things to know about ten cardiovascular disease risk factors" published since 2020. This 2022 version provides the perspective of ASPC members and includes updated sentinel references (i.e., applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful dietary intake, physical inactivity, dyslipidemia, pre-diabetes/diabetes, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis (with smoking as a potential contributor to thrombosis), kidney dysfunction and genetics/familial hypercholesterolemia. Other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the ASPC "Ten things to know about ten cardiovascular disease risk factors - 2022" to provide a tabular overview of things to know about ten of the most common CVD risk factors applicable to preventive cardiology and provide ready access to applicable guidelines and sentinel reviews.