Jay Khambhati

Comprehensive primary prevention of cardiovascular disease in women

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in women. Historically, medical research has focused on male patients, and subsequently, there has been decreased awareness of the burden of ASCVD in females until recent years. The biological differences between sexes and differences in societal expectations defined by gender roles contribute to gender differences in ASCVD risk factors. With these differing risk profiles, risk assessment, risk stratification, and primary preventive measures of ASCVD are different in women and men. In this review article, clinicians will understand the risk factors unique to women, such as preeclampsia, gestational diabetes, and those that disproportionately affect them such as autoimmune disorders. With these conditions in mind, the approach to ASCVD risk assessment and stratification in women will be discussed. Furthermore, the literature behind the effects of primary preventive measures in women, including lifestyle modifications, aspirin, statins, and anticoagulation, will be reviewed. The aim of this review article was to ultimately improve ASCVD primary prevention by reducing gender disparities through education of physicians.

Biomarkers to Predict Cardiovascular Death

This article reviews biomarkers that have been shown to identify subjects at increased risk for cardiovascular death within the general population, in those with established coronary artery disease, and in those with heart failure. Use of biomarkers for risk stratification for sudden cardiac death continues to evolve. It seems that a multimarker strategy for risk stratification using simple measures of circulating proteins and usual clinical risk factors, particularly in patients with known coronary artery disease, can be used to identify patients at near-term risk of death. Whether similar strategies in the general population will prove to be cost-effective needs to be investigated.

Angina and Ischemia in Women with No Obstructive Coronary Artery Disease

Ischemic heart disease (IHD) continues to be a major health threat to women worldwide. Sex-specific differences in IHD presentation, pathophysiology, treatment, and outcomes have increasingly been identified. While IHD care has focused around detection and treatment of obstructive coronary artery disease (CAD), it is clear that symptomatic patients with evidence of ischemia do not always have obstructive CAD. This problem appears to disproportionately impact women; compared to men, women who present with acute coronary syndrome/unstable angina as well as stable angina are more likely to have non-obstructive CAD on coronary angiography, and yet have a high IHD morbidity and mortality. Data indicates that coronary microvascular dysfunction (CMD), due to endothelial and non-endothelial dependent mechanisms, may be an explanation in at least half of these symptomatic women who have evidence of myocardial ischemia. CMD is associated with adverse cardiovascular outcomes, including myocardial infarction, stroke, and heart failure. This chapter focuses on CMD diagnosis and treatment (pharmacological and non-pharmacological approaches) in women with no obstructive CAD.

The art of cardiovascular risk assessment

Cardiovascular disease (CVD) remains the leading cause of death in the United States. Healthcare expenditures have been principally allocated toward treatment of CVD at the end of the health/disease continuum, rather than toward health promotion and disease prevention. A focused effort on both primordial and primary prevention can promote cardiovascular health and reduce the burden of CVD. Risk‐factor assessment for predicting atherosclerotic CVD events serves as the foundation of preventive cardiology and has been driven by population‐based scoring algorithms based on traditional risk factors. Incorporating individual nontraditional risk factors, biomarkers, and selective use of noninvasive measures may help identify more at‐risk patients as well as truly low‐risk individuals, allowing for better targeting of treatment intensity. Using a combination of validated population‐based atherosclerotic CVD risk‐assessment tools, nontraditional risk factors, social health determinants, and novel markers of atherosclerotic disease, we should be able to improve our ability to assess CVD risk. Through scientific evidence, clinical judgment, and discussion between the patient and clinician, we can implement an effective evidence‐based strategy to assess and reduce CVD risk.

Immunotherapy for the prevention of atherosclerotic cardiovascular disease: Promise and possibilities

Cardiovascular disease remains the leading cause of death worldwide with coronary atherosclerotic heart disease being the largest contributor. The mechanisms behind the presence and progression of atherosclerosis remain an area of intense scientific focus. Immune dysregulation and inflammation are key contributors to the development of an atherosclerotic plaque and its progression to acute coronary syndromes. Increased circulating levels of biomarkers of systemic inflammation including hsCRP are correlated with a higher cardiovascular risk. Targeting specific inflammatory pathways implicated in atherosclerotic plaque formation is an exciting area of ongoing research. Target specific therapies directed at pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and CCL2 have demonstrated slowing in the progression of atherosclerosis in animal models and improved cardiovascular outcomes in human subjects. Most notably, treatment with the monoclonal antibody canakinumab, which directly targets and neutralizes IL-1β, was recently shown to be associated with reduced risk of adverse cardiovascular events compared to placebo in a randomized, placebo-controlled trial. Several other therapies including colchicine, methotrexate and leukotriene inhibitors demonstrate the potential for lowering cardiovascular risk through immunomodulation, though further studies are needed. Understanding the role of inflammation in atherosclerosis and the development of targeted immunotherapies continues to be an evolving area of research that is rapidly becoming clinically relevant for the 21st century cardiac patient.

Comparison of the Association between High-Sensitivity Troponin I and Adverse Cardiovascular Outcomes in Patients with Versus Without Chronic Kidney Disease

It is unknown whether the association of high-sensitivity troponin I (hs-TnI) with adverse cardiovascular outcomes varies by the presence of chronic kidney disease (CKD). We examined the association of hs-TnI with adverse cardiovascular outcomes in those with and without CKD in 4,107 (mean age, 64 years; 63% men; 20% black) patients from the Emory Cardiovascular Biobank who underwent coronary angiography. CKD (n = 1,073) was defined as estimated glomerular filtration rate <60 ml/min/1.73 m2 or urine albumin/creatinine ratio >30 mg/g at baseline. Cox regression was used to compute hazard ratios (HR) for the association between hs-TnI levels (per doubling of hs-TnI: log2[hs-TnI] + 1) and death, cardiovascular death, and major adverse cardiac events (MACE), separately. Hs-TnI was a stronger predictor of death (CKD: HR 1.23, 95% confidence interval [CI] 1.15 to 1.31; no CKD: HR 1.11, 95% CI 1.05 to 1.17, p-interaction = 0.023), cardiovascular death (CKD: HR 1.24, 95% CI 1.14 to 1.34; no CKD: HR 1.15, 95% CI 1.07 to 1.22, p-interaction = 0.12), and MACE (CKD: HR 1.18, 95% CI 1.11 to 1.25; no CKD: HR 1.11, 95% CI 1.06 to 1.16, p-interaction = 0.095) in CKD compared with non-CKD. The association between hs-TnI and death in patients with CKD was stronger for patients without obstructive coronary artery disease (no obstructive coronary artery disease: HR 1.60, 95% CI 1.27 to 2.01; obstructive coronary artery disease: HR 1.19, 95% CI 1.11 to 1.27, p-interaction = 0.041). In conclusion, hs-TnI is a stronger predictor of adverse cardiovascular events in patients who have CKD than those without, even in the absence of obstructive coronary artery disease. Hs-TnI may identify CKD patients who are high risk for adverse cardiovascular outcomes in whom aggressive risk factor modification strategies are warranted.

CENTRAL OBESITY PREDICTS CIRCULATING PROGENITOR CELL LEVELS

Background: Obesity is a pro-inflammatory state leading to endothelial cell injury and dysfunction. In particular, central (android) obesity is associated with increased cardiovascular disease risk. Bone marrow derived CD34+ progenitor cells (PC) levels are elevated in patients with high body mass

ASSOCIATION BETWEEN CIRCULATING PROGENITOR CELLS AND OUTCOMES IN PATIENTS WITH CORONARY ARTERY DISEASE

Background: Circulating hematopoietic enriched progenitor cells (PCs) predict adverse cardiovascular outcomes in patients with coronary artery disease (CAD). The additive predictive role of endothelial enriched PCs expressing vascular endothelial growth factor receptor (VEGF) remains controversial.

Endothelial Dysfunction and Essential Hypertension

Systemic hypertension is a chronic disorder of cardiovascular system characterized by an increase in systemic vascular resistance (SVR). Although the level of blood pressure is a product of SVR and cardiac output, it is the former which is responsible for chronic blood pressure elevation. A number of biochemical, biophysical, and neuro-humoral factors participate in the maintenance of SVR. Whatever the underlying molecular mechanism may be for elevated SVR, the end consequence is endothelial dysfunction. Normal endothelium promotes vasodilation and prevention of local thrombotic phenomena whereas abnormal endothelium promotes vasoconstriction and thrombotic processes. One of the basic pathophysiological aberrations in hypertension is abnormal endothelial function. A number of blood pressure lowering strategies (life-style modification and or anti-hypertensive drugs) result in reversing endothelial dysfunction in hypertension. Thus, endothelial function is considered both as a mechanism and a therapeutic target in hypertension. This review summarizes the physiology and pathophysiology of endothelium in hypertension.