Coronary Artery Calcium Dispersion and Cause-Specific Mortality.

Coronary artery calcium (CAC) measures subclinical atherosclerosis and improves risk stratification. CAC characteristics-including vessel(s) involved, number of vessels, volume, and density-have been shown to differentially impact risk. We assessed how dispersion-either the number of calcified vessels or CAC phenotype (diffuse, normal, and concentrated)-impacted cause-specific mortality. The CAC Consortium is a retrospective cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC scoring. This study included patients with CAC >0 (n = 28,147). CAC area, CAC density, and CAC phenotypes (derived from the index of diffusion = 1 - [CAC in most concentrated vessel/total Agatston score]) were calculated. The associations between CAC characteristics and cause-specific mortality were assessed. The participant details included (n = 28,147): mean age 58.3 years, 25% female, 89.6% White, and 66% had 2+ calcified vessels. Diabetes, hypertension, and hyperlipidemia were predictors of multivessel involvement (p <0.001). After controlling for the overall CAC score, those with 4-vessel CAC involvement had more CAC area and less dense calcifications than those with 1-vessel. There was a graded increase in all-cause and cardiovascular disease (CVD)- and CHD-specific mortality as the number of calcified vessels increased. Among those with ≥2 vessels involved (n = 18,516), a diffuse phenotype was associated with a higher CVD-specific mortality and had a trend toward higher all-cause and CHD-specific mortality than a concentrated CAC phenotype. Diffuse CAC involvement was characterized by less dense calcification, more CAC area, multiple coronary vessel involvement, and presence of certain traditional risk factors. There is a graded increase in all-cause and CVD- and CHD-specific mortality with increasing CAC dispersion.

Coronary computed tomography angiography in patients with stable coronary artery disease.

The treatment of coronary artery disease (CAD), which is defined by stable anatomical atherosclerotic and functional alterations of epicardial vessels or microcirculation, focuses on managing intermittent angina symptoms and preventing major adverse cardiovascular events with optimal medical therapy. When patients with known CAD present with angina and no acute coronary syndrome, they have historically been evaluated with a variety of noninvasive stress tests that utilize electrocardiography, radionuclide scintigraphy, echocardiography, or magnetic resonance imaging for determining the presence and extent of inducible myocardial ischemia. Patient event-free survival, however, is largely driven by the coronary atherosclerotic disease burden, which is not directly assessed by functional testing. Direct evaluation of coronary atherosclerotic disease by coronary computed tomography angiography (coronary CTA) has emerged as the first line noninvasive imaging modality as it improves diagnostic accuracy and positively influences clinical management. Compared to functional assessment of CAD, coronary CTA-guided management results in improved patient outcomes by facilitating prevention of myocardial infarction. Other strengths of coronary CTA include detailed atherosclerotic plaque characterization and the ability to assess functional significance of specific lesions, which may further improve risk assessment and prognosis and lead to more appropriate referrals for additional testing, such as invasive coronary angiography.

The Miami Heart Study (MiHeart) at Baptist Health South Florida, A prospective study of subclinical cardiovascular disease and emerging cardiovascular risk factors in asymptomatic young and middle-aged adults: The Miami Heart Study: Rationale and Design.

OBJECTIVE: The Miami Heart Study (MiHeart) at Baptist Health South Florida is an ongoing, community-based, prospective cohort study aimed at characterizing the prevalence, characteristics, and prognostic value of diverse markers of early subclinical coronary atherosclerosis and of various potential demographic, psychosocial, and metabolic risk factors. We present the study objectives, detailed research methods, and preliminary baseline results of MiHeart. METHODS: MiHeart enrolled 2,459 middle-aged male and female participants from the general population of the Greater Miami Area. Enrollment occurred between May 2015 and September 2018 and was restricted to participants aged 40-65 years free of clinical cardiovascular disease (CVD). The baseline examination included assessment of demographics, lifestyles, medical history, and a detailed evaluation of psychosocial characteristics; a comprehensive physical exam; measurement of multiple blood biomarkers including measures of inflammation, advanced lipid testing, and genomics; assessment of subclinical coronary atherosclerotic plaque and vascular function using coronary computed tomography angiography, the coronary artery calcium score, carotid intima-media thickness, pulse wave velocity, and peripheral arterial tonometry; and other tests including 12-lead electrocardiography and assessment of pulmonary function. Blood samples were biobanked to facilitate future ancillary research. RESULTS: MiHeart enrolled 1,261 men (51.3%) and 1,198 women (48.7%). Mean age was 53 years, 85.6% participants were White and 47.4% were of Hispanic/Latino ethnicity. The study included 7% individuals with diabetes, 33% with hypertension, and 15% used statin therapy at baseline. Overweight or obese participants comprised 72% of the population and 3% were smokers. Median 10-year estimated atherosclerotic CVD risk using the Pooled Cohort Equations was 4%. CONCLUSION: MiHeart will provide important, novel insights into the pathophysiology of early subclinical atherosclerosis and further our understanding of its role in the genesis of clinical CVD. The study findings will have important implications, further refining current cardiovascular prevention paradigms and risk assessment and management approaches moving forward.

Inflammation, atrial fibrillation, and the potential role for colchicine therapy.

Increasing evidence suggests that the "NACHT-LRR and PYD domain-containing protein 3" (NLRP3) inflammasome plays an important role in atherosclerotic cardiovascular disease (ASCVD). Recent preclinical evidence has suggested that the NLRP3 inflammasome may play a prominent role in the pathogenesis of atrial fibrillation (AF). As such, the therapies that have shown efficacy in reducing ASCVD events may also prove beneficial in AF. In this article, we review the findings that implicate the NLRP3 inflammasome in the pathogenesis of AF, discuss existing evidence behind the use of anti-inflammatory agents for AF, and discuss the future role that colchicine and other anti-inflammatory agents may play in the prevention and treatment of AF.

The Johns Hopkins Ciccarone Center's expanded 'ABC's approach to highlight 2020 updates in cardiovascular disease prevention.

In recent years, improvement in outcomes related to cardiovascular disease is in part due to the prioritization and progress of primary and secondary prevention efforts. The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease expanded 'ABC's approach is used to highlight key findings in Preventive Cardiology from 2020 and further emphasize the importance of cardiovascular prevention. This simplified approach helps clinicians focus on the most relevant and up to date recommendations for optimizing cardiovascular disease risk through accurate risk assessment and appropriate implementation of lifestyle, behavioral and pharmacologic interventions. While 2020 not only provided practice changing updates by way of clinical guidelines and randomized controlled trials on topics related to antithrombotic and lipid lowering therapy, diabetes management and risk assessment, it also provided promising data on how to improve dietary and exercise adherence and manage genetic risk. By providing clinicians with a systematic approach to cardiovascular prevention and key highlights from the prior year, the goal of significantly reducing the burden of cardiovascular disease worldwide can be achieved.

2019 clinical trials in lipid lowering.

PURPOSE OF REVIEW: Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy trials, many of which provide a unique opportunity to further reduce low-density lipoprotein cholesterol (LDL-C) levels and ASCVD risk on top of statin therapy, and in doing so further decrease the number of future major adverse cardiovascular events. RECENT FINDINGS: Although statin therapy has been the mainstay of treatment for lowering LDL-C levels for many years, many individuals require additional or alternative options for further reducing their risk. Trials on previously studied therapies, such as PCSK9 inhibitors, and new therapies, including inclisiran, bempedoic acid and icosapent ethyl demonstrate significant potential for further lowering of LDL-C levels and risk for events on top of maximally tolerated statin therapy with favourable side effect profiles. SUMMARY: As therapies for ASCVD prevention continue to emerge, clinicians will need to identify the appropriate treatment for individuals based on their estimated risk and risk-enhancing factors. When statin therapy is either not sufficient or patients do not tolerate adequate statin therapy, relying on newer therapies, such as PCSK9-inhibitors, inclisiran, bempedoic acid and icosapent ethyl, will be critical to maximize risk factor profiles to reduce adverse outcomes.

Same evidence, varying viewpoints: Three questions illustrating important differences between United States and European cholesterol guideline recommendations.

In 2018, the AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol was released. Less than one year later, the 2019 ESC/EAS Dyslipidemia Guideline was published. While both provide important recommendations for managing atherosclerotic cardiovascular disease (ASCVD) risk through lipid management, differences exist. Prior to the publication of both guidelines, important randomized clinical trial data emerged on non-statin lipid lowering therapy and ASCVD risk reduction. To illustrate important differences in guideline recommendations, we use this data to help answer three key questions: 1) Are ASCVD event rates similar in high-risk primary and stable secondary prevention? 2) Does imaging evidence of subclinical atherosclerosis justify aggressive use of statin and non-statin therapy (if needed) to reduce LDL-C levels below 55 â€‹mg/dL as recommended in the European Guideline? 3) Do LDL-C levels below 70 â€‹mg/dL achieve a large absolute risk reduction in secondary ASCVD prevention? The US guideline prioritizes both the added efficacy and cost implications of non-statin therapy, which limits intensive therapy to individuals with the highest risk of ASCVD. The European approach broadens the eligibility criteria by incorporating goals of therapy in both primary and secondary prevention. The current cost and access constraints of healthcare worldwide, especially amidst a COVID-19 pandemic, makes the European recommendations more challenging to implement. By restricting non-statin therapy to a subgroup of high- and, in particular, very high-risk individuals, the US guideline provides primary and secondary ASCVD prevention recommendations that are more affordable and attainable. Ultimately, finding a common ground for both guidelines rests on our ability to design trials that assess cost-effectiveness in addition to efficacy and safety.

Summarizing 2019 in Cardiovascular Prevention Using the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease's 'ABC's Approach.

In 2019, Preventive Cardiology welcomed many exciting discoveries that improve our ability to reduce the burden of cardiovascular disease (CVD) nationwide. Not only did 2019 further clarify how various environmental exposures and innate and acquired risk factors contribute to the development of CVD, but it also provided new guidelines and therapeutics to more effectively manage existing CVD. Cardiovascular disease prevention requires the prioritization of early and effective detection of CVD in order to implement aggressive lifestyle and pharmacologic therapies, which can slow, halt, or even reverse the progression of the disease. To help streamline and simplify the process of CVD prevention, The Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease has historically adopted an 'ABC' approach, which focuses on optimizing individual CVD risk through lifestyle, behavioral, and pharmacologic interventions. Given the practice changing research and innovation from the past year, this article intends to summarize the Ciccarone Center's key takeaways from CVD prevention in 2019 utilizing our expanded 'ABC' approach.

Association of Erectile Dysfunction with Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE: Erectile dysfunction has been associated with atrial fibrillation in cross-sectional studies, but the association of erectile dysfunction with incident atrial fibrillation is less well established. This study aimed to determine whether erectile dysfunction is independently associated with incident atrial fibrillation after adjusting for conventional risk factors. METHODS: We studied 1760 male participants (mean age 68 ± 9 years) from the Multi-Ethnic Study of Atherosclerosis (MESA), who completed self-reported erectile dysfunction assessment at MESA exam 5 (2010-2012). Cumulative incidence of atrial fibrillation was estimated by Kaplan-Meier analysis. Cox proportional hazards regression was used to calculate the unadjusted and adjusted hazard ratios (HR) using 3 models in which variables were added in a stepwise manner. In model 3, HR was adjusted for age, race and ethnicity, education, smoking status, alcohol use, systolic blood pressure, body mass index, diabetes, anti-hypertensive medication use, lipid-lowering medication use, total cholesterol, and estimated glomerular filtration rate. RESULTS: During the median follow-up of 3.8 (interquartile range, 3.5-4.2) years, 94 cases of incident atrial fibrillation were observed. There was a significant difference between males with and without erectile dysfunction for cumulative incident atrial fibrillation rates at 4 years (9.6 vs 2.9%, P < .01). In the fully adjusted model, erectile dysfunction remained associated with incident atrial fibrillation (model 3; HR, 1.66; 95% confidence interval 1.01-2.72, P = .044). CONCLUSIONS: Among older male participants in this prospective study, we found that self-reported erectile dysfunction was associated with incident atrial fibrillation.

The association between left main coronary artery calcium and cardiovascular-specific and total mortality: The Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: Left main (LM) coronary artery disease is associated with greater myocardial infarction-related mortality, however, coronary artery calcium (CAC) scoring does not account for disease location. We explored whether LM CAC predicts excess mortality in asymptomatic adults. METHODS: Cause-specific cardiovascular and all-cause mortality was studied in 28,147 asymptomatic patients with non-zero CAC scores in the CAC Consortium. Multivariate regression was performed to evaluate if the presence and burden of LM CAC predict mortality after adjustment for clinical risk factors and the Agatston CAC score. We further analyzed the per-unit hazard associated with LM CAC in comparison to CAC in other arteries. RESULTS: The study population had mean age of 58.3 ±â€¯10 years and CAC score of 301 ±â€¯631. LM CAC was present in 21.7% of the cases. During 312,398 patient-years of follow-up, 1,907 deaths were observed. LM CAC was associated with an increased burden of clinical risk factors and total CAC, and was independently predictive of increased hazard for all-cause (HR 1.2 [1.1, 1.3]) and cardiovascular disease death (HR 1.3 [1.1, 1.5]). The hazard for death increased proportionate to the percentage of CAC localized to the LM. On a per-100 Agatston unit basis, LM CAC was associated with a 6-9% incremental hazard for death beyond knowledge of CAC in other arteries. CONCLUSIONS: The presence and high burden of left main CAC are independently associated with a 20-30% greater hazard for cardiovascular and total mortality in asymptomatic adults, arguing that LM CAC should be routinely noted in CAC score reports when present.

Erectile dysfunction links to cardiovascular disease-defining the clinical value.

Despite many advances over the last few decades, cardiovascular disease (CVD) remains the leading cause of death globally, with men afflicted at an earlier age than women. In a bid to reduce the global burden of morbidity and mortality due to CVD, emphasis has been placed on prevention, particularly on widespread promotion of ideal cardiovascular health behaviors and advancing strategies to identify and treat high-risk individuals who may benefit from aggressive preventive therapy. Erectile dysfunction is a highly prevalent condition that has been demonstrated to share the same risk factors as clinical CVD, and to have independent predictive value for future CVD events. Importantly, subclinical atherosclerosis appears to precede vascular ED by a decade or longer, with ED preceding clinical CVD such as myocardial infarction and stroke in temporal sequence by about 2-5 years. Crucially, since ED may represent the first presentation of otherwise "healthy" men to care providers, a clinical diagnosis of vascular ED may represent a unique opportunity to identify high risk individuals, intervene, and thus prevent progression to clinical CVD. This review summarizes up-to-date evidence of the relationship between ED and subclinical and clinical CVD, and details the position of current guidelines and clinical recommendations on the role of ED assessment in CVD prevention. Finally, this review proposes a clinical framework for the incorporation of ED into standard CVD risk assessment in middle-age men.

Harnessing mHealth technologies to increase physical activity and prevent cardiovascular disease.

Research into prevention of cardiovascular disease has increasingly focused on mobile health (mHealth) technologies and their efficacy in helping individuals adhere to heart-healthy recommendations, including daily physical activity levels. By including the use of mHealth technologies in the discussion of physical activity recommendations, clinicians empower patients to play an active daily role in modifying their cardiovascular risk-factor profile. In this review, we critically evaluate the mHealth and physical activity literature to determine how these tools may lower cardiovascular risk while providing real-time tracking, feedback, and motivation on physical activity levels. We analyze the various domains-including user knowledge, social support, behavioral change theory, and self-motivation-that potentially influence the effectiveness of smartphone applications to impact individual physical activity levels. In doing so, we hope to provide a thorough overview of the mHealth landscape, in addition to highlighting many of the administrative, reimbursement, and patient-privacy challenges of using these technologies in patient care. Finally, we propose a behavioral change model and checklist for clinicians to assist patients in utilizing mHealth technology to best achieve meaningful changes in daily physical activity levels.

Is diabetes mellitus equivalent to atherosclerotic cardiovascular disease from a healthcare cost perspective? Insights from the Medical Expenditure Panel Survey: 2010-2013.

Diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) both increase the risk for a major adverse cardiac event, and are therefore considered priority conditions clinically. Although guidelines encourage clinicians to treat them similarly, many researchers do not consider DM an ASCVD risk-equivalent. However, from a healthcare system standpoint it is more important to determine whether DM is an economic burden equivalent to ASCVD. Using data from the Household Component of the 2010-2013 Medical Expenditure Panel Survey, we determined that the diagnosis of DM yields significantly lower healthcare expenditures and resource utilization when compared with ASCVD. In fact, the healthcare cost associated with DM alone is almost $1000 less than ASCVD. That being said, the cost and resource utilization was highest among those individuals diagnosed with ASCVD+DM, underscoring the importance of primary and secondary prevention to help detect individuals early and initiate proper lifestyle and aggressive therapeutic managements.

Prognostic value of exercise capacity among men undergoing pharmacologic treatment for erectile dysfunction: The FIT Project.

BACKGROUND: Vascular erectile dysfunction (ED) has been identified as a potentially useful risk factor for predicting future cardiovascular events, particularly in younger men. Because these men typically score more favorably on traditional cardiovascular disease risk assessment tools, there exists a gap in knowledge for how to most appropriately identify those men who would benefit from more aggressive treatments. To date, no studies have examined the impact of fitness on cardiovascular outcomes in men with ED. This study sought to examine the prognostic impact of maximal exercise capacity on cardiovascular-related outcomes in men ages 40 to 60 years being treated for ED. HYPOTHESIS: We hypothesized that there would be an independent association between higher baseline fitness level and lower cardiovascular events. METHODS: We analyzed 1152 men with pharmacy claims file-confirmed active pharmacologic treatment for ED from the Henry Ford Exercise Testing (FIT) Project (1991-2009). All patients were free of coronary heart disease and heart failure, and underwent clinician-referred exercise stress testing, with fitness measured in metabolic equivalents of task (METs). Multivariable Cox proportional hazard models adjusted for traditional cardiovascular risk factors were used to study the association between fitness and all-cause mortality, major adverse cardiovascular events (MACE) (defined as myocardial infarction or revascularization), and incident type 2 diabetes mellitus. RESULTS: The mean age of the population was 53 years, with 39% African Americans. In multivariable analysis, each 1 MET of fitness was associated with a 16% lower risk of death (hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76-0.94, P = 0.002), and a nonsignificant reduction in MACE (HR: 0.89, 95% CI: 0.79-1.003, P = 0.048), and incident diabetes (HR: 0.92, 95% CI: 0.85-1.01, P = 0.129). CONCLUSIONS: Higher baseline fitness is associated with improved cardiovascular prognosis in a population of middle-aged men treated for ED.

Relation of Exercise Capacity to Risk of Development of Diabetes in Patients on Statin Therapy (the Henry Ford Exercise Testing Project).

High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p <0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p <0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use.

Favorable cardiovascular risk factor profile is associated with lower healthcare expenditure and resource utilization among adults with diabetes mellitus free of established cardiovascular disease: 2012 Medical Expenditure Panel Survey (MEPS).

BACKGROUND AND AIMS: Given the prevalence and economic burden of diabetes mellitus (DM), we studied the impact of a favorable cardiovascular risk factor (CRF) profile on healthcare expenditures and resource utilization among individuals without cardiovascular disease (CVD), by DM status. METHODS: 25,317 participants were categorized into 3 mutually-exclusive strata: "Poor", "Average" and "Optimal" CRF profiles (≥4, 2-3, 0-1 CRF, respectively). Two-part econometric models were utilized to study cost data. RESULTS: Mean age was 45 (48% male), with 54% having optimal, 39% average, and 7% poor CRF profiles. Individuals with DM were more likely to have poor CRF profile vs. those without DM (OR 7.7, 95% CI 6.4, 9.2). Individuals with DM/poor CRF profile had a mean annual expenditure of $9,006, compared to $6,461 among those with DM/optimal CRF profile (p < 0.001). CONCLUSIONS: A favorable CRF profile is associated with significantly lower healthcare expenditures and utilization in CVD-free individuals across DM status, suggesting that these individuals require aggressive individualized prescriptions targeting lifestyle modifications and therapeutic treatments.

Vascular Erectile Dysfunction and Subclinical Cardiovascular Disease.

PURPOSE OF REVIEW: We review the recent literature on the hypothesized temporal relationship between subclinical cardiovascular disease (CVD), vascular erectile dysfunction (ED), and clinical CVD. In addition, we combine emerging research with expert consensus guidelines such as The Princeton Consensus III to provide a preventive cardiologist's perspective toward an ideal approach to evaluating and managing CVD and ED risk in patients. RECENT FINDINGS: Development of ED was found to occur during the progression from subclinical CVD to clinical CVD. A strong association was observed between subclinical CVD as assessed by coronary artery calcium (CAC) and carotid plaque and subsequent ED, providing evidence for the role of subclinical CVD in predicting ED. ED is also identified as a substantial independent risk factor for overt clinical CVD, and ED symptoms may precede CVD symptoms by 2-3 years. SUMMARY: Given the body of evidence on the relationship between subclinical CVD, ED, and clinical CVD we recommend that all men with vascular ED should undergo cardiovascular risk assessment. We further recommend using CAC scores for advanced risk assessment in patients at low-intermediate to intermediate risk (5-20% CVD risk), with risk driving subsequent lifestyle and pharmacologic treatment decisions.