Evolution of More Aggressive LDL-Cholesterol Targets and Therapies for Cardiovascular Disease Prevention.

Over the last half-century, discussions on the exact targets for low-density lipoprotein cholesterol (LDL-C) reduction have evolved towards a more aggressive approach with lower LDL-C targets, particularly for high-risk patients with pre-existing atherosclerotic cardiovascular disease (ASCVD). A wealth of cardiovascular outcome trials have shown the efficacy of statin therapy in general, as well as the incremental impact of high-intensity statin therapy in particular. More recent trials have further demonstrated the impact of non-statin therapies, including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and, most recently, bempedoic acid, on reducing ASCVD outcomes. The availability of these and other newer therapies has prompted clinicians to strive for lower LDL-C targets to address residual ASCVD risk after statin therapy. This paper will provide an overview of the historical trends in lipid management and therapeutics and review the current state of evidence for lower LDL-C targets in clinical guidelines and recommendations.

Distinguishing aortic valve thrombus from Libman-Sacks endocarditis in antiphospholipid syndrome: imaging and management.

Aortic valve (AV) thrombus, a rare complication of antiphospholipid syndrome (APLS), is important to distinguish from Libman-Sacks endocarditis because of its responsiveness to anticoagulation. This may be attributed to immunopathologic differences underpinning their development. We present the case of a 45-year-old woman with high-risk primary APLS who developed an AV mass and was taken for valvular repair surgery but found to have pure thrombus and normal valve leaflets. In such cases, a trial of conservative management with anticoagulation may be adequate. Echocardiography, computed tomography and MRI findings suggestive of thrombus without endocarditis are presented. A literature review of histopathologic, imaging and treatment implications of pure AV thrombus in the context of APLS is included.

Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes.

PURPOSE OF REVIEW: When treating patients with diabetes mellitus (DM), the benefits of antiplatelet therapy in preventing cardiovascular disease must be weighed against an increased risk of bleeding. Recent trials have sought to determine both the optimal anti-platelet regimen for patients with DM, and who specifically requires medication among the DM population. This paper will review recent trials and evidence recommending the use of antiplatelet therapy in the prevention of cardiovascular disease in patients with diabetes. RECENT FINDINGS: Seven notable trials assessed the effectiveness of antiplatelet therapy in the DM population. The ASCEND trial concluded 100 mg aspirin/day reduced rates of serious vascular events (OR 0.88, p < 0.01) but also increased rates of major bleeding events (OR 1.29, p < 0.01). The DAPT study revealed a longer dual antiplatelet regimen (30 months vs. 18 months) after coronary stent placement was more effective in reducing rates of stent thrombosis (0.5% vs. 1.1%, p = 0.06) and rates of myocardial infarction (3.5% vs. 4.8%, p = 0.06). DECLARE DIABETES showed that adding cilostazol to dual antiplatelet therapy after a coronary stent procedure reduced rates of in-stent and in-segment late loss and increased rates of revascularization (p < 0.04). In PEGASUS-TIMI, daily ticagrelor demonstrated reduced rates of major adverse cardiovascular and cerebrovascular events (OR 0.84, p < 0.04). The DAVID trial compared daily picotamide with daily aspirin therapy, finding reduced mortality rates in the picotamide group (OR 0.55, p < 0.05). Lastly, ACUITY found bivalirudin monotherapy resulted in lower rates of major bleeding events when compared to a glycoprotein IIb/IIa inhibitor and heparin or bivalirudin combination regimen (p < 0.01). Dual antiplatelet therapy guidelines still typically revolve around aspirin, but an increasing number of studies have demonstrated other drugs that may have a role in preventing atherosclerotic cardiovascular disease while decreasing the risk of major bleeding. Overall, it is wise to weigh the cardiovascular risk of a DM patient before prescribing antiplatelet medication. More research is necessary to determine a universal drug or combination of drugs that is safe and effective for DM patients.

Preexisting Right Ventricular Dysfunction Is Associated With Higher Postoperative Cardiac Complications and Longer Hospital Stay in High-Risk Patients Undergoing Nonemergent Major Vascular Surgery.

OBJECTIVES: To evaluate whether the presence of preexisting right ventricular (RV) dysfunction in high-risk patients undergoing nonemergent major vascular surgery is associated independently with higher incidents of postoperative cardiac complications and a longer length of hospital stay. DESIGN: Retrospective chart review. SETTING: Single-center university hospital setting. PARTICIPANTS: The patient population consisted of those identified as American Society of Anesthesiologists classification III and above who had a preoperative echocardiogram within 1 year of undergoing nonemergent major vascular surgery between January 2010 and May 2017. MEASUREMENTS AND MAIN RESULTS: After multivariate analyses, RV dysfunction (RVD) is associated independently with a higher incidence of postoperative major cardiac complications with an odds ratio = 6.3 (95% confidence interval [CI], 1.0-38.5; p = 0.046). In addition, patients with RVD had a 50% longer length of stay than those without RVD (incident rate ratio [95% CI], 1.5 [1.2-1.8]; p < 0.001). CONCLUSION: In this retrospective study of high-risk patients undergoing major vascular surgery, RV dysfunction was associated independently with a higher incidence of postoperative major cardiovascular events and longer length of hospital stays. Based on current findings, the prognostic value of RVD extends beyond the cardiac surgical cohort. Knowledge in management of patients with RVD in the perioperative setting should be understood by all anesthesiologists. Of note, a future study with a larger sample size is needed to validate the current findings given the small sample size of this study.

Percutaneous Coronary Intervention in Familial Hypercholesterolemia Is Understudied.

Familial hypercholesterolemia (FH) is a common heritable condition in which mutations of genes governing cholesterol metabolism result in elevated LDL levels and accelerated atherosclerosis. The treatment of FH focuses on lipid lowering drugs to decrease patients' cholesterol levels and reduce their risk of cardiovascular events. Even with optimal medical therapy, some FH patients will develop coronary atherosclerosis, suffer myocardial infarction, and require revascularization. Yet, the revascularization of FH patients has not been widely studied. Here we review FH, identify unanswered questions in the interventional management of FH patients, and explore barriers and opportunities for answering these questions. Further research is needed in this neglected but important topic in interventional cardiology.

Multivessel percutaneous coronary intervention without contrast agents.

Contrast-induced nephropathy (CIN) following coronary angiography is associated with significant morbidity and mortality. Contrast media volume is the key risk factor for CIN in patients with chronic kidney disease undergoing coronary angiography and interventions. Very often, coronary interventions are avoided in such high-risk patients because of possible significant adverse clinical outcomes. We present a case demonstrating use of intravascular ultrasound (IVUS) to guide multivessel percutaneous coronary intervention (PCI) performed without any contrast administration in a patient with extreme risk for CIN. With the availability of advanced imaging of the coronary arteries such as high definition IVUS, contrast free PCI is a feasible approach and is associated with significant advantages of reducing or eliminating the development of CIN following PCI. This case report highlights the key practical aspects of performing contrast-free PCI and the challenges associated with such approach. © 2015 Wiley Periodicals, Inc.

Left atrial septal pouch in cryptogenic stroke.

BACKGROUND: The left atrial septal pouch (LASP), an anatomic variant of the interatrial septum, has uncertain clinical significance. We examined the association between LASP and ischemic stroke subtypes in patients undergoing transesophageal echocardiography (TEE). METHODS: We determined the prevalence of LASP among consecutive patients who underwent TEE at our institution. Patients identified with ischemic strokes were further evaluated for stroke subtype using standard and modified criteria from the Trial of Org 10172 in Acute Stroke Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke, cryptogenic stroke, and non-stroke patients using prevalence ratios (PR). RESULTS: The mean age of all 212 patients (including stroke and non-stroke patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the 75 patients who were worked-up for stroke at our institution during study period, we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of LASP among cryptogenic stroke patients (using standard and modified TOAST criteria) was increased compared to the prevalence among other ischemic stroke patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1-3.1, and 30 vs. 10%, p = 0.04; PR = 2.2, 95% CI = 1.2-4.1, respectively). CONCLUSION: In this population of relatively young patients, prevalence of LASP was increased in cryptogenic stroke compared to stroke patients of other subtypes. These findings suggest LASP is associated with cryptogenic stroke, which should be verified by future large-scale studies.

Atherosclerosis in chronic kidney disease: lessons learned from glycation in diabetes.

In diabetes, glycation is a nonenzymatic posttranslational modification resulting from the bonding of a sugar molecule with a protein or lipid followed by oxidation, resulting in the development of advanced glycation end products (AGE). Like glycation, carbamylation is a posttranslational protein modification that is associated with AGE formation. Glycation of extracellular matrix proteins and low-density lipoprotein with subsequent deposition in the vessel wall could contribute to inflammatory response and atheroma formation. It is logical to extrapolate that carbamylation may result in modification of vessel wall proteins similar to glycation, and predispose to atherosclerosis.

Adiponectin and vulnerable atherosclerotic plaques.

High-risk plaques that are vulnerable to rupture demonstrate distinct morphological characteristics. They are differentiated from the lesions responsible for stable coronary artery disease by their large necrotic cores, thin-inflamed fibrous caps, and positive remodeling. Adiponectin is an adipocytokine that is reduced in obesity and type 2 diabetes. Hypoadiponectinemia has been associated with an increased risk of coronary artery disease and acute coronary syndrome in several though not all studies. The involvement of adiponectin provides clues to the inflammatory and atherogenic mechanisms associated with pathological coronary disease progression.