Faculty Bibliography

In the second part of this JACC State-of-the-Art Review, an early and sustainable preventive care plan is described for cardiometabolic-based chronic disease. This plan can improve cardiometabolic health by targeting early mechanistic events to decrease the risk for certain cardiovascular diseases (e.g., coronary heart disease, heart failure, and atrial fibrillation). Included are various prevention modalities, intensive lifestyle interventions, pharmacotherapy and cardiovascular outcome trial evidence, and bariatric/metabolic procedures. A tactical approach of implementing published clinical practice guidelines/algorithms for early behavioral, adiposity, and dysglycemia targeting is emphasized, as well as relevant educational and research implications.

BACKGROUND:Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described. METHODS AND RESULTS/RESULTS:The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy. The primary aim of this analysis was to determine predictors of meeting trial goals for LDL-C (low-density lipoprotein cholesterol, goal <70 mg/dL) or systolic blood pressure (SBP, goal <140 mm Hg) at 1 year post-randomization. We included all randomized participants in the ISCHEMIA trial with baseline and 1-year LDL-C and SBP values by January 28, 2019. Among the 3984 ISCHEMIA participants (78% of 5179 randomized) with available data, 35% were at goal for LDL-C, and 65% were at goal for SBP at baseline. At 1 year, the percent at goal increased to 52% for LDL-C and 75% for SBP. Adjusted odds of 1-year LDL-C goal attainment were greater with older age (odds ratio [OR], 1.11 [95% CI, 1.03-1.20] per 10 years), lower baseline LDL-C (OR, 1.19 [95% CI, 1.17-1.22] per 10 mg/dL), high-intensity statin use (OR, 1.30 [95% CI, 1.12-1.51]), nonwhite race (OR, 1.32 [95% CI, 1.07-1.63]), and North American enrollment compared with other regions (OR, 1.32 [95% CI, 1.06-1.66]). Women were less likely than men to achieve 1-year LDL-C goal (OR, 0.68 [95% CI, 0.58-0.80]). Adjusted odds of 1-year SBP goal attainment were greater with lower baseline SBP (OR, 1.27 [95% CI, 1.22-1.33] per 10 mm Hg) and with North American enrollment (OR, 1.35 [95% CI, 1.04-1.76]). CONCLUSIONS:In ISCHEMIA, older age, male sex, high-intensity statin use, lower baseline LDL-C, and North American location predicted 1-year LDL-C goal attainment, whereas lower baseline SBP and North American location predicted 1-year SBP goal attainment. Future studies should examine the effects of sex disparities, international practice patterns, and provider behavior on risk factor control.

PURPOSE OF REVIEW/OBJECTIVE:In recent years, there have been several cardiovascular outcomes trials (CVOT) of two new classes of glucose-lowering medications: sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). It is important examine their potential for cardiovascular benefit and possible side effects among patients with type 2 diabetes (T2D) mellitus. RECENT FINDINGS/RESULTS:The current article reviews the findings of recent CVOT of SGLT2-i and GLP-1 RA, including their impact on cardiovascular events and relevant side effects. SUMMARY/CONCLUSIONS:For all T2D patients, with or without established cardiovascular disease, the SGLT2-i have demonstrated impressive reductions in hospitalization for heart failure and renoprotection. For T2D patients with established cardiovascular disease, SGLT2-i demonstrated an additional benefit of reduced major adverse cardiac events, on top of reductions in hospitalizations for heart failure, renoprotection, and in some instances, mortality. Similarly, all GLP-1 RA CVOTs demonstrated noninferiority compared with placebo for safety. In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.

BACKGROUND:The impact of thrombocytopenia on revascularization and outcomes in patients presenting with acute myocardial infarction remains poorly understood. We sought to evaluate associations between thrombocytopenia, in-hospital management, bleeding, and cardiovascular outcomes in patients hospitalized for acute myocardial infarction in the United States. METHODS:Patients hospitalized from 2004 to 2014 with a primary diagnosis of acute myocardial infarction were identified from the National Inpatient Sample. Management of acute myocardial infarction was compared between patients with and without thrombocytopenia. Multivariable logistic regression models were used to estimate odds of in-hospital adverse events stratified by thrombocytopenia and adjusted for demographics, cardiovascular risk factors, comorbidities, and treatment. RESULTS:A total of 6,717,769 patients were hospitalized with a primary diagnosis of acute myocardial infarction and thrombocytopenia was reported in 219,351 (3.3%). Patients with thrombocytopenia were older, more likely to have other medical comorbidities, were more likely to undergo coronary artery bypass grafting (28.8% vs. 8.2%, p<0.001), and were less likely to receive a drug eluting stent (15.5% vs. 29.5%, p<0.001). After multivariable adjustment, thrombocytopenia was independently associated with nearly two-fold increased odds of in-hospital mortality (aOR 1.91, 95% CI 1.86-1.97). Thrombocytopenia was also independently associated with ischemic stroke, cardiogenic shock, cardiac arrest and bleeding complications. CONCLUSIONS:Patients with thrombocytopenia in the setting of acute myocardial infarction had increased odds of bleeding, cardiovascular outcomes, and mortality compared with patients without thrombocytopenia. Future investigations to mitigate the poor prognosis of patients with acute myocardial infarction and thrombocytopenia are warranted.

CONTEXT/BACKGROUND:For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the pre-specified subgroup of diabetic patients. EVIDENCE ACQUISITION/METHODS:We review the published literature focusing on the atherogenic nature of diabetes, and available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in diabetic patients. EVIDENCE SYNTHESIS/RESULTS:The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in diabetic patients. CONCLUSIONS:The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

BACKGROUND:While progress in the prevention of cardiovascular disease (CVD) has been noted over the past several decades, there are still those who develop CVD earlier in life than others. OBJECTIVE:We investigated traditional and lifestyle CVD risk factors in young to middle-aged patients compared to older ones with obstructive coronary artery disease (CAD). METHODS:A retrospective analysis of patients with a new diagnosis of obstructive CAD undergoing coronary intervention was performed. Young to middle-aged patients were defined as those in the youngest quartile (n = 281, mean age 50 ± 6 years, 81% male) compared to the other three older quartiles combined (n = 799, mean age 69 ± 7.5 years, 71% male). Obstructive CAD was determined by angiography. RESULTS:Young to middle-aged patients compared to older ones were more likely to be male (p < 0.01), smokers (21 vs. 9%, p < 0.001), and have a higher body mass index (31 ± 6 vs. 29 ± 6 kg/m2, p < 0.001). Younger patients were less likely to eat fruits, vegetables, and fish and had fewer controlled CVD risk factors (2.7 ± 1.2 vs. 3.0 ± 1.0, p < 0.001). Compared to older patients, higher levels of psychological stress (aOR 1.6, 95% CI 1.1-2.4), financial stress (aOR 1.8, 95% CI 1.3-2.5), and low functional capacity (aOR 3.3, 95% CI 2.4-4.5) were noted in the young to middle-aged population as well. CONCLUSION/CONCLUSIONS:Lifestyle in addition to traditional CVD risk factors should be taken into account when evaluating risk for development of CVD in a younger population.

BACKGROUND:Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. METHODS:A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. RESULTS:Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. CONCLUSIONS:Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Background: Women with early-stage breast cancer are at excess risk of cardiovascular disease (CVD) due to deleterious therapy-induced direct as well as indirect perturbations across the entire cardiovascular system. CVD events such as acute myocardial infarction (AMI) induce a systemic (host) inflammatory response that accelerates underlying atherosclerotic disease. Whether an AMIinduced systemic response affects cancer progression is not known.
Method(s): In a prospective case cohort study, we evaluated the relationship between a new onset, post-diagnosis CVD event (e.g., AMI, stroke, heart failure) and recurrence in 3802 patients with early-stage breast cancer. To assess causality, we tested the effects of surgically-induced AMI on breast cancer progression and metastasis in mouse models of breast cancer.
Result(s): A new onset CVD event was associated with increased risk of recurrence compared to patients not experiencing an event (HR: 1.69; 95% confidence interval, 1.15 to 2.50). In preclinical models, surgically-induced AMI significantly accelerated tumor growth compared to sham surgery controls (p<0.001), as well as metastatic burden (p<0.05). Tumors of AMI mice had an altered tumor microenvironment and tumor immune cell landscape, driven by the increased availability, recruitment, intratumoral accumulation and immunosuppressive phenotype of CD11b⁺ Ly6C^high myeloid cells.
Conclusion(s): A CVD event accelerates breast cancer progression in humans and mice. These data provide new mechanistic insight into cross-disease communication as a mediator of breast cancer pathogenesis