Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity
or surgery
, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be ...at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors
. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6C
monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6C
monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.
Introduction There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal ...chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD. Methods We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy (TACT) strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. Conclusions There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor.
There is concern that patients taking renin–angiotensin–aldosterone system inhibitors have an increased risk of Covid-19, because angiotensin-converting enzyme 2 is a receptor for the virus. This ...study showed no increase in likelihood of a positive Covid-19 test or severe Covid-19 in patients taking any of five common classes of antihypertensive drugs.
A new cardiometabolic-based chronic disease (CMBCD) model is presented that provides a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and ...mitigate the development and ravages of cardiovascular disease. In the first part of this JACC State-of-the-Art Review, a framework is presented for CMBCD, focusing on 3 primary drivers (genetics, environment, and behavior) and 2 metabolic drivers (adiposity and dysglycemia) with applications to 3 cardiovascular endpoints (coronary heart disease, heart failure, and atrial fibrillation). Specific mechanistic pathways are presented configuring early primary drivers with subsequent adiposity, insulin resistance, β-cell dysfunction, and metabolic syndrome, leading to cardiovascular disease. The context for building this CMBCD model is to expose actionable targets for prevention to achieve optimal cardiovascular outcomes. The tactical implementation of this CMBCD model is the subject of second part of this JACC State-of-the-Art Review.
Type 2 diabetes mellitus (T2D) is a major risk factor for cardiovascular disease (CVD), the most common cause of death in T2D. Yet, <50% of U.S. adults with T2D meet recommended guidelines for CVD ...prevention. The burden of T2D is increasing: by 2050, approximately 1 in 3 U.S. individuals may have T2D, and patients with T2D will comprise an increasingly large proportion of the CVD population. The authors believe it is imperative that we expand the use of therapies proven to reduce CVD risk in patients with T2D. The authors summarize evidence and guidelines for lifestyle (exercise, nutrition, and weight management) and CVD risk factor (blood pressure, cholesterol and blood lipids, glycemic control, and the use of aspirin) management for the prevention of CVD among patients with T2D. The authors believe appropriate lifestyle and CVD risk factor management has the potential to significantly reduce the burden of CVD among patients with T2D.
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The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or ...severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.
In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).
Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio HR, 0.89 95% CI, 0.61-1.30; severe ischemia HR, 0.83 95% CI, 0.57-1.21;
=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 95% CI, 0.86-1.69 versus mild/no ischemia; HR for severe ischemia, 1.37 95% CI, 0.98-1.91;
=0.04 for trend,
=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 95% CI, 1.06-6.98) and MI (HR, 3.78 95% CI, 1.63-8.78) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% 95% CI, 0.2%-12.4%), but 4-year all-cause mortality was similar.
Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.
Given the intersection between diabetes mellitus and cardiovascular disease (CVD), pharmacologic agents used to treat type 2 diabetes mellitus must show cardiovascular safety. Comorbid conditions, ...including heart failure and chronic kidney disease, are increasingly prevalent in patients with diabetes; therefore, they also play a large role in drug safety. Although biguanides, sulfonylurea, glitazones, and dipeptidyl peptidase 4 inhibitors have variable effects on cardiovascular events, sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have consistently shown safety and reduction in cardiovascular events in patients with established CVD. These medications are becoming essential tools for cardioprotection for patients with diabetes and CVD. They may also have roles in primary prevention and renal protection. This paper will review the cardiovascular impact, adverse effects, and possible mechanisms of action of pharmacologic agents used to treat patients with type 2 diabetes.
Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air ...pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary modification, omega-3 fatty acid supplementation, and indoor and in-vehicle air conditioning as viable strategies to minimize adverse health effects. There is currently insufficient data to recommend specific personal approaches to reduce the adverse cardiovascular effects of noise pollution. Public health advisories for periods of extreme heat or cold should be observed, with limited evidence supporting a warm ambient home temperature and physical activity as strategies to limit the cardiovascular harms of temperature extremes. Perfluoroalkyl and polyfluoroalkyl substance exposure can be reduced by avoiding contact with perfluoroalkyl and polyfluoroalkyl substance-containing materials; blood or plasma donation and cholestyramine may reduce total body stores of perfluoroalkyl and polyfluoroalkyl substances. However, the cardiovascular impact of these interventions has not been examined. Limited utilization of pesticides and safe handling during use should be encouraged. Finally, vasculotoxic metal exposure can be decreased by using portable air cleaners, home water filtration, and awareness of potential contaminants in ground spices. Chelation therapy reduces physiological stores of vasculotoxic metals and may be effective for the secondary prevention of cardiovascular disease.
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.
At a median of 2.2 years, patients with stable coronary artery disease and advanced kidney disease who were treated with an invasive strategy of coronary angiography with revascularization if ...indicated did not have a lower risk of death or MI than those who were treated with a conservative strategy of medical therapy alone.
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