Genetic Risk Assessment for Atherosclerotic Cardiovascular Disease: A Guide for the General Cardiologist.

Genetic testing for cardiovascular (CV) disease has had a profound impact on the diagnosis and evaluation of monogenic causes of CV disease, such as hypertrophic and familial cardiomyopathies, long QT syndrome, and familial hypercholesterolemia. The success in genetic testing for monogenic diseases has prompted special interest in utilizing genetic information in the risk assessment of more common diseases such as atherosclerotic cardiovascular disease (ASCVD). Polygenic risk scores (PRS) have been developed to assess the risk of coronary artery disease, which now include millions of single-nucleotide polymorphisms that have been identified through genomewide association studies. Although these PRS have demonstrated a strong association with coronary artery disease in large cross-sectional population studies, there remains intense debate regarding the added value that PRS contributes to existing clinical risk prediction models such as the pooled cohort equations. In this review, we provide a brief background of genetic testing for monogenic drivers of CV disease and then focus on the recent developments in genetic risk assessment of ASCVD, including the use of PRS. We outline the genetic testing that is currently available to all cardiologists in the clinic and discuss the evolving sphere of specialized cardiovascular genetics programs that integrate the expertise of cardiologists, geneticists, and genetic counselors. Finally, we review the possible implications that PRS and pharmacogenomic data may soon have on clinical practice in the care for patients with or at risk of developing ASCVD.

Invasive Management of Out of Hospital Cardiac Arrest.

Out of hospital cardiac arrest (OHCA) is a major cause of morbidity and mortality worldwide. Clinical decision making is extremely difficult in this understudied patient population with high prevalence of neurological injury and inexorable shock states. As such, there are uncertain benefits from therapies available in the cardiac catheterization laboratory. Fear of futility and public reporting often affects decision making and can result in risk aversion. This review focuses on invasive management in OHCA care, with particular focus on coronary angiography, coronary revascularization, and mechanical support. Guidelines recommend emergency coronary angiography in patients with ST-segment elevations on ECG after OHCA, while the role of coronary angiography in patients without ST-segment elevations is less clear. Similar uncertainty remains in the appropriate revascularization strategy in these patients. As in other areas of cardiology, there is a growing interest in the role of mechanical circulatory support after OHCA, though the available literature shows mixed results. The many uncertainties associated with treating the patient with OHCA highlight the importance of clinical decision support tools and treatment algorithms in the care of this population. This review focuses on invasive management in OHCA care, with particular focus on coronary angiography, coronary revascularization, and mechanical support.

Lipoprotein(a): A Lipoprotein Whose Time Has Come.

OPINION STATEMENT: Cardiovascular disease is a leading cause of morbidity and mortality in the USA and around the world. While we are now able to achieve significant low-density lipoprotein cholesterol (LDL-C) lowering with current therapies, many patients remain at risk for cardiovascular disease (CVD). Elevated lipoprotein(a) [Lp(a)] has been shown to be an independent risk factor for CVD and accounts for some of the residual CVD risk after LDL-C lowering in several large clinical trials. Moreover, there is now strong evidence supporting the causal relationship between Lp(a) and aortic stenosis as well as peripheral arterial disease. Despite the growing interest in this lipoprotein, the current therapeutic options for Lp(a) reduction are limited. Our general approach in patients with elevated Lp(a) levels is to aggressively manage other modifiable cardiovascular risk factors including lifestyle modification, consideration of aspirin therapy, and LDL-C lowering. Unfortunately, there are conflicting reports on how effective this strategy is at reducing the risk for cardiovascular events attributed to elevated Lp(a). As a result, targeted Lp(a)-lowering strategies are needed. Lp(a) therapeutics is an active area of research with several promising classes of pharmacotherapies under investigation to address this causal biomarker.

Lower Extremity Acute Bacterial Skin and Soft Tissue Infection Following Total Knee Arthroplasty.

BACKGROUND: Although total knee arthroplasty (TKA) is one of the most common orthopedic procedures, its association with subsequent acute bacterial skin and soft tissue infections (ABSSTIs) in the ipsilateral limb has not been studied. METHODS: This was a retrospective study of patients with prior unilateral TKA who were diagnosed with ABSSTI 4 weeks or more postoperatively in the absence of surgical site infection. The odds of ABSSTI in the TKA limb was compared to that of the contralateral "control" limb in the same patient in the presence or absence of local predisposing factors for ABSSTI in the lower extremities (e.g., chronic venous insufficiency). RESULTS: Of 94 patients studied, 58 (62%) were women; mean age was 74.5 years. The mean body mass index was 33.1kg/m(2). One or more local predisposing factors were present in 53 (56.4%) patients. The mean interval between TKA and ABSSTI was 65.1 months (range: 1-239 months), with cellulitis alone diagnosed in 88 (94%) patients. ABSSTI involved the TKA limb of 68 (72.3%) patients and was significantly more likely to be diagnosed in the same limb in the absence of local predisposing factors (36 of 41 patients, odds ratio = 7.2, 95% CI: 2.8-23.5); the odds of TKA limb involvement was also higher in the presence of such factors but did not quite reach statistical significance (odds ratio = 1.5, 95% CI: 0.8-2.8). CONCLUSIONS: TKA appears to predispose to ABSSTIs in the ipsilateral lower extremity often years after the procedure, particularly in the absence of other local factors.

Targeting lipoprotein (a): an evolving therapeutic landscape.

Robust epidemiologic and genetic studies have solidified the role of lipoprotein (a) [Lp(a)] as an independent and causal risk factor for cardiovascular disease. The increased cardiovascular risk of Lp(a) is mediated through both proatherogenic and prothrombotic/antifibrinolytic mechanisms. Several societies recommend Lp(a) screening for patients with high cardiovascular risk, although no consensus exists on the management of patients with elevated Lp(a). However, numerous pharmacologic approaches are being evaluated that have the potential to reduce Lp(a) and will be the focus of this review. The majority of these interventions have been developed for other lipid-lowering indications, but also lower Lp(a). There are also novel therapies in development that specifically target Lp(a). The efficacy of these therapies varies, and their role in the evolving lipoprotein therapeutic landscape has yet to be determined. Nevertheless, targeted Lp(a) reduction is certainly intriguing and will likely continue to be an active area of investigation in the future.

Aspirin for cardioprotection and strategies to improve patient adherence.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in North America. Aspirin therapy has proven clinical effectiveness in the prevention and treatment of CVD and is one of the most widely used drugs nationwide. However, despite the medication's popularity and utility, adherence to a proper aspirin regimen is suboptimal, resulting in adverse health outcomes and increased health care costs. Our review outlines current knowledge on aspirin therapy adherence, causes of nonadherence, and strategies available to increase adherence to aspirin and medications in general. We demonstrate that, indeed, aspirin adherence rates are suboptimal, ranging from 72% to 92%, and that a combination of patient- and medication-related factors contribute to nonadherence. A multidimensional approach involving patient education and medication innovations to reduce aspirin side effects is imperative to improving rates of aspirin therapy adherence.