Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association.

Lipoprotein(a) [Lp(a)] is a well-recognized, independent risk factor for atherosclerotic cardiovascular disease, with elevated levels estimated to be prevalent in 20% of the population. Observational and genetic evidence strongly support a causal relationship between high plasma concentrations of Lp(a) and increased risk of atherosclerotic cardiovascular disease-related events, such as myocardial infarction and stroke, and valvular aortic stenosis. In this scientific statement, we review an array of evidence-based considerations for testing of Lp(a) in clinical practice and the utilization of Lp(a) levels to inform treatment strategies in primary and secondary prevention.

Greater than expected reduction in low-density lipoprotein-cholesterol (LDL-C) with bempedoic acid in a patient with heterozygous familial hypercholesterolemia (HeFH).

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that reduces levels of low-density lipoprotein-cholesterol (LDL-C) in the plasma by inhibition of cholesterol synthesis in hepatic cells, which leads to up-regulation of hepatic LDL receptors. Bempedoic acid is approved as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. In this case study, we describe a patient with HeFH who had a prior excellent response to statin but unable to take the same, and a less than expected response to PCSK9i, in whom initiation of bempedoic acid led to a substantial reduction of LDL-C. Our findings suggest that patients who are quite responsive to statins may also be quite responsive to bempedoic acid, a medication that works in the same biochemical pathway as HMG-CoA reductase inhibitors. Additionally, this medication may be particularly effective at lowering LDL-C among individuals not on background statin therapy.

A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies.

INTRODUCTION: Clinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety. METHODS: We summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12. RESULTS: Across the studies, evolocumab reduced LDL-C by a mean 55-61% from baseline to week 12; ezetimibe lowered LDL-C by 18-20% from baseline (mean difference = 38-43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60-104 mg/dL with evolocumab vs. 17-35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments. CONCLUSIONS: Evolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.

Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association.

Lipoprotein(a) [Lp(a)] is a well-recognized, independent risk factor for atherosclerotic cardiovascular disease, with elevated levels estimated to be prevalent in 20% of the population. Observational and genetic evidence strongly support a causal relationship between high plasma concentrations of Lp(a) and increased risk of atherosclerotic cardiovascular disease-related events, such as myocardial infarction and stroke, and valvular aortic stenosis. In this scientific statement, we review an array of evidence-based considerations for testing of Lp(a) in clinical practice and the utilization of Lp(a) levels to inform treatment strategies in primary and secondary prevention.

The STatin Adverse Treatment Experience Survey: Experience of patients reporting side effects of statin therapy.

BACKGROUND: It is important to understand patients' experiences of statin-associated adverse effects to potentially identify those at risk for stopping treatment. OBJECTIVE: The goal of the STatin Adverse Treatment Experience survey was to describe patients' experiences after reporting ≥1 recent statin-associated adverse event and identify opportunities to improve adherence and outcomes. METHODS: The survey was developed in 3 stages: qualitative item development, pilot evaluation of initial item performance, and quantitative evaluation using a large commercial sample. Respondents with self-reported high cholesterol who had taken a statin in the past 2 years and experienced ≥1 statin-associated symptom in the past 6 months were included (N = 1500). RESULTS: Mean age was 58 years, 40.3% were men, and 43.2% had tried ≥2 statins. Many had clinical comorbidities associated with increased risk for cardiovascular disease (atherosclerotic cardiovascular disease, 22.5%; diabetes, 25.8%; hypertension, 56.0%). The most important patient-reported reasons for continuing current statin therapy (n = 1168; 77.9%) were avoiding a heart attack or stroke, lowering cholesterol, and doctor recommendation. Being bothered by and not being able to tolerate side effects were the main reasons respondents discontinued statins (n = 332; 22.1%). Respondents who discontinued statins reported significantly higher mean Symptom Severity (10.6 vs 8.7, P < .001) and Impact Severity scores (11.8 vs 9.8, P < .001) compared with those who continued. CONCLUSION: The STatin Adverse Treatment Experience survey highlights the importance of patients' adverse experiences with statins and how symptom and impact scores affect decisions to continue or discontinue therapy. These data provide a foundation to increase providers' awareness of statin tolerability from the patient's perspective and encourage benefit-risk discussions.

Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study.

BACKGROUND AND AIMS: Diabetes increases risk for atherosclerotic cardiovascular disease (ASCVD). Current guidelines do not recommend measuring lipoprotein(a), another ASCVD risk factor, in these individuals. We examined the association of lipoprotein(a) levels with incident ASCVD events in persons with and without diabetes or prediabetes. METHODS: Lipoprotein(a) and other ASCVD risk factors were measured at baseline (1996-1998) in the biracial Atherosclerosis Risk in Communities study; participants without prevalent ASCVD (coronary heart disease or stroke) were monitored ∼15 years for incident ASCVD events. RESULTS: Of 9871 eligible participants (mean age 63 years; 5816 women; 2155 African Americans), 1543 had diabetes and 3615 had prediabetes. Cumulative ASCVD incidence rates (event/1000-person years) were higher in participants with diabetes (26%) or prediabetes (13%) than in nondiabetic individuals (10%, p < 0.001). When comparing highest to lowest lipoprotein(a) categories (≥50 mg/dL vs. ≤10 mg/dL), increasing lipoprotein(a) levels were significantly associated with increasing incident ASCVD events in Caucasian participants with prediabetes (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.07-1.69); p = 0.03) and diabetes (HR = 1.42; 95% CI 1.10-1.84; p < 0.01), but not those with normal fasting blood glucose. Adding lipoprotein(a) to Pooled Cohort Equation variables improved risk prediction in persons with diabetes (Δ in area under the receiver operating characteristic curve [AUC] 0.0087, net reclassification index [NRI] 0.1761) and prediabetes (ΔAUC 0.0025, NRI 0.0938). CONCLUSIONS: In this biracial cohort, elevated lipoprotein(a) levels in Caucasian individuals with diabetes or prediabetes were associated with further increased ASCVD risk. Adding lipoprotein(a) to traditional risk factors improved ASCVD risk prediction.

Case reports of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition nonresponse.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of monoclonal antibodies, reduces low-density lipoprotein cholesterol levels and improves cardiovascular outcomes. Given the short time frame, these agents have been available for use; reports of nonresponse to the PCSK9 inhibitor therapy are scarce in literature. We describe 2 cases with substantially lesser than expected low-density lipoprotein cholesterol lowering on PCSK9 therapy. Nonresponse to PCSK9 inhibition was attributed to autosomal recessive hypercholesterolemia (secondary to low-density lipoprotein receptor adaptor protein 1 mutation) and plasmapheresis after PCSK9 inhibitor drug injections. Additional PCSK9 inhibitor nonresponders are likely to emerge as the use of these agents increases overtime.

Correction to: Cardiovascular Disease Prevention: Training Opportunities, the Challenges, and Future Directions.

The original version of this article contains errors in Table 3. "At least 1 project/publication in the year" and "> 1 publication per year" have been switched under the titles of "Clinical Track" and "Physician-Scientist track".

Cardiovascular Disease Prevention: Training Opportunities, the Challenges, and Future Directions.

PURPOSE: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, necessitating major efforts in prevention. This review summarizes the currently available training opportunities in CVD prevention for fellows-in-training (FITs) and residents. We also highlight the challenges and future directions for CVD prevention as a field and propose a structure for an inclusive CVD prevention training program. RECENT FINDINGS: At present, there is a lack of centralized training resources for FITs and residents interested in pursuing a career in CVD prevention. Training in CVD prevention is not an accredited subspecialty fellowship by the American Council of Graduate Medical Education (ACGME). Although there are several independent training programs under the broad umbrella of CVD prevention focusing on different aspects of prevention, there is no unified curriculum or training. More collaborative efforts are needed to identify CVD prevention as an ACGME-accredited subspecialty fellowship. Providing more resources can encourage and produce more leaders in this essential field.

Association of low-density lipoprotein pattern with mortality after myocardial infarction: Insights from the TRIUMPH study.

BACKGROUND: Studies of incident coronary heart disease risk within low-density lipoprotein (LDL) subclass (small, dense vs large, buoyant) have shown mixed results. No prospective cohort study has examined the association of small, dense, or large, buoyant LDL with mortality after myocardial infarction (MI). OBJECTIVE: The objective of the study was to examine association of LDL pattern after MI and death. METHODS: In 2476 patients hospitalized for MI, LDL pattern (A [large, buoyant], A/B [mixed], and B [small, dense]) was established by ultracentrifugation using Vertical Auto Profile. Using time-to-event analysis, we examined the association with 5-year mortality within LDL patterns, after adjusting for important patient and treatment characteristics. We additionally adjusted for LDL cholesterol (LDL-C) and triglyceride levels and used directly measured LDL-C and non-high-density lipoprotein cholesterol as exposures. RESULTS: Patterns A, A/B, and B were present in 39%, 28%, and 33% of patients, respectively, with incident rates (per 1000 patient-years) of 50, 34, and 24 for all-cause and 24, 19, and 10 for CV mortality. The hazard ratios (95% confidence interval) with LDL patterns A/B and B compared with pattern A were 0.77 (0.61, 0.99) and 0.67 (0.51, 0.88) for all-cause, 0.94 (0.67, 1.33) and 0.69 (0.46, 1.03) for cardiovascular, and 0.64 (0.45, 0.91) and 0.65 (0.45, 0.93) for noncardiovascular mortalities, respectively. Results were similar when further adjusted for LDL-C and triglycerides, or with LDL-C and non-high-density lipoprotein cholesterol as exposures. CONCLUSION: Compared with LDL pattern A, pattern B was significantly associated with reduced all-cause and non-CV mortalities with a trend for lower CV mortality after MI, independent of LDL-C and triglycerides.

Developing Optimized Treatment Plans for Patients with Dyslipidemia in the Era of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapeutics.

This educational content was derived from a live satellite symposium at the American College of Physicians Internal Medicine Meeting 2017 in San Diego, California (online at http://courses.elseviercme.com/acp/702e). This activity will focus on optimized treatment plans for patients with dyslipidemia in the era of proprotein convertase subtilisin/kexin type 9 inhibitor therapeutics. Low-density lipoprotein cholesterol has been identified as an important therapeutic target to prevent the progression of atherosclerotic disease; however, only 1 of every 3 adults with high low-density lipoprotein cholesterol has the condition under control. Expert faculty on this panel will discuss the science of proprotein convertase subtilisin/kexin type 9 inhibitors and aid physicians in the best practices to achieve low-density lipoprotein cholesterol target in their patients.

Safety of Alirocumab (A PCSK9 Monoclonal Antibody) from 14 Randomized Trials.

Previous individual trials of alirocumab (a PCSK9 monoclonal antibody) showed significant low-density lipoprotein cholesterol reductions with overall treatment-emergent adverse event (TEAE) rates comparable with controls. This analysis evaluated safety data from 14 trials (4 phase 2 and 10 phase 3, 8 to 104 weeks; n = 5,234), in 2 pools according to control (placebo/ezetimibe). Overall, 3,340 patients received alirocumab (4,029 patient-years' exposure), 1,276 received placebo, and 618 received ezetimibe. Incidence of deaths, serious TEAEs, discontinuations because of TEAEs, and overall TEAEs were similar between alirocumab and control groups. Alirocumab was associated with a higher incidence of local injection site reactions (7.4% vs 5.3% with placebo; 3.1% vs 2.3% with ezetimibe), pruritus (1.3% vs 0.4% placebo; 0.9% vs 0.5% ezetimibe), and upper respiratory tract infection signs and symptoms (2.1% vs 1.1% placebo; 1.3% vs 0.8% ezetimibe). Incidence of musculoskeletal, neurologic, neurocognitive, ophthalmologic, hepatic events, and TEAEs related to diabetes/diabetes complications was similar between alirocumab and control groups. In a prespecified analysis of phase 3 studies, adjudicated major adverse cardiovascular events (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, and unstable angina requiring hospitalization) occurred in 1.8% alirocumab versus 2.6% placebo patients (hazard ratio 0.69, 95% confidence interval 0.43 to 1.11) and 2.8% alirocumab versus 1.5% ezetimibe patients (hazard ratio 1.4, 95% confidence interval 0.65 to 3.02). In conclusion, pooled safety data from 14 trials demonstrate that alirocumab is generally well tolerated with a favorable safety profile.

Provider understanding of the 2013 ACC/AHA cholesterol guideline.

BACKGROUND: Providers' understanding of the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline in clinical practice is not known. METHODS: We designed a questionnaire, which was administered to internal medicine, family practice, cardiology, and endocrinology providers at 21 venues across the United States. We compared responses between providers in training or practice and between specialists (cardiology and endocrinology) and nonspecialists (internal medicine and family practice). RESULTS: Response rate was 72.1% (543 of 725). About 43% of the providers in training and 48% of those in practice indicated having read the guideline. Almost 50% in each group were unable to identify the 4 statin benefit groups and a large proportion (41% in training and 49% in practice) were not aware of the ≥7.5% 10-year risk threshold for discussion regarding statin therapy. Most (∼85%) were unaware of the 4 outcomes assessed by the 10-year ASCVD risk equation. About 36% of the providers in training and 48% in practice could identify a patient with familial hypercholesterolemia and start a discussion regarding statin therapy. Only 27.6% of the providers in training and 40.4% in practice recommended repeating a lipid panel 6-8 weeks after starting statins in a patient with recent myocardial infarction. Similar gaps were noted when comparing specialists to nonspecialists. CONCLUSION: Most providers do not completely understand the 2013 ACC/AHA cholesterol guideline. As an unintended consequence, providers are moving away from lipid testing to document response and adherence to statin therapy. Efforts are needed to address these gaps.

A dataset to assess providers׳ knowledge and attitudes towards the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guideline.

We previously examined provider׳s understanding of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline (DOI: http://dx.doi.org/10.1016/j.jacl.2015.11.002)(Virani et al., 2013) [1], and also assessed whether a case-based educational intervention could improve providers׳ knowledge gaps and attitudes towards the guideline (DOI: 10.1016/j.atherosclerosis.2015.12.044) (Pokharel, et al., 2016) [2]. Here we describe the dataset that we used to examine our objectives.

Lipids and bariatric procedures Part 2 of 2: scientific statement from the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and Obesity Medicine Association (OMA).

Bariatric procedures generally improve dyslipidemia, sometimes substantially so. Bariatric procedures also improve other major cardiovascular risk factors. This 2-part Scientific Statement examines the lipid effects of bariatric procedures and reflects contributions from authors representing the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and the Obesity Medicine Association (OMA). Part 1 was published in the Journal of Clinical Lipidology, and reviewed the impact of bariatric procedures upon adipose tissue endocrine and immune factors, adipose tissue lipid metabolism, as well as the lipid effects of bariatric procedures relative to bile acids and intestinal microbiota. This Part 2 reviews: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies, that may occur after bariatric procedures.

Closing The Gap: Improving Trauma Care On The Ukrainian Battlefield.

Since early 2014, Ukraine has been involved in a violent social and political revolution that has taken more than 7,000 lives. Many of these deaths were due to limited field medical care and prolonged evacuation times because the Ukrainian military has been slow to adopt standard combat medical processes. We deployed with the US Army's 173rd Airborne Brigade to train soldiers in the National Guard of Ukraine (NGU) on combat first aid. We discovered that a major deficiency limiting the quality of trauma care and evacuation is an endemic lack of prior coordination and planning. The responsibility for this coordination falls on military leaders; therefore, we delivered medical operations training to officers of the NGU unit and observed great improvement in medical care sustainment. We recommend systematic leader education in best medical practices be institutionalized at all levels of the Ukrainian Army to foster sustained improvement and refinement of trauma care.