Dyslipidemia management in women of reproductive potential: An expert clinical consensus from the national lipid association.

Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.

Understanding the spectrum of cardiovascular risk in women - A primer for prevention.

Cardiovascular disease (CVD) is the leading cause of death in women worldwide and the lifetime risk of CVD in women is similar to men. However, the pathophysiology of CVD varies between women and men necessitating a sex-specific understanding of cardiovascular (CV) risk. A belief that women have a lower CVD risk than men, and an underrepresentation in clinical research for many years has led to a paucity of evidence in the prevention and management of CVD in women. Many recent efforts have tried to bridge the gap. As a result, we now know that traditional risk factors impact CVD risk differently in women when compared with men. There are also numerous sex-specific and pregnancy related risk factors that modify the risk and can predict the future development of CVD in women. This is important as risk calculators, in general, tend to misclassify risk in young women with nontraditional CVD risk factors. To address this, guidelines have introduced the concept of risk enhancers that can suggest a higher risk. The use of coronary artery calcium score can further accurately delineate risk in these women, leading to an appropriate matching of therapy to underlying risk. This review discusses implementation strategies that are essential to mitigate disparities in CVD outcomes and optimizing CVD risk in women.

GLP-1 Receptor Agonists and Cardiovascular Disease: What Do Clinicians Need to Know?

PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining importance due to their effects on cardiovascular parameters. This review discusses the findings of dedicated cardiovascular outcome trials of GLP-1RAs and summarizes their utility to help clinicians understand their role in cardiovascular disease. RECENT FINDINGS: Patients with diabetes mellitus are at an increased risk of cardiovascular disease. Cardiovascular outcome trials have shown GLP-1RAs decrease the primary composite outcome of the first occurrence of major adverse cardiovascular events (MACE) in patients with diabetes. Additionally, select GLP-1RAs have also shown improved cardiovascular outcomes in patients without diabetes who are either overweight (BMI ≥ 27), or obese (BMI ≥ 30). There have also been encouraging results in patients with heart failure with preserved ejection fraction. There is increasing evidence showing GLP-1RAs are beneficial across the cardiometabolic spectrum of disease. Implementation of these therapeutics into clinical practice is important to improve cardiovascular risk.

Oral PCSK9 Inhibitors.

PURPOSE OF REVIEW: In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. RECENT FINDINGS: The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C. Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C-lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events.

Is there a role for earlier use of combination therapy?

As the global population ages and cardiovascular risk factors rise, we can expect a continued increase in atherosclerotic disease. Low-density lipoprotein cholesterol (LDL-C) reduction is a cornerstone of cardiovascular risk reduction with strong, causal evidence indicating that the greatest benefit is derived from early and large decreases in LDL-C. Despite the adoption of statins as the backbone of lipid-therapy regimens, numerous studies and registry analyses reveal our collective inability to achieve LDL-C goals in high-risk patients. Combination therapy with ezetimibe has been shown to result in statistically significant decreases in LDL-C level, atheroma volume, and cardiovascular adverse event rates. A major barrier to implementing an upfront combination therapy approach is the perceived side effects from therapeutic agents although multiple studies show that a therapeutic patient-physician relationship could overcome this issue. Novel agents such as PCSK-9 inhibitors, bempedoic acid, and inclisiran have the potential to achieve similar outcomes although additional research is needed regarding the cost effectiveness of these approaches. Despite these hurdles, there is a role for the newer agents early in the disease course of high-risk patients such as those with markedly elevated LDL-C >190 mg/dL and FH. The implementation of upfront combination therapy, especially in high-risk patients, will decrease clinical inertia while allowing for earlier consideration of newer, effective agents to decrease cardiovascular burden.

Identification and Management of Atherosclerotic Cardiovascular Disease Risk in South Asian Populations in the U.S.

South Asians (SAs, individuals with ancestry from Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) are among the fastest growing ethnic subgroups in the United States. SAs typically experience a high prevalence of diabetes, abdominal obesity, and hypertension, among other cardiovascular disease risk factors, which are often under recognized and undermanaged. The excess coronary heart disease risk in this growing population must be critically assessed and managed with culturally appropriate preventive services. Accordingly, this scientific document prepared by a multidisciplinary group of clinicians and investigators in cardiology, internal medicine, pharmacy, and SA-centric researchers describes key characteristics of traditional and nontraditional cardiovascular disease risk factors, compares and contrasts available risk assessment tools, discusses the role of blood-based biomarkers and coronary artery calcium to enhance risk assessment and prevention strategies, and provides evidenced-based approaches and interventions that may reduce coronary heart disease disparities in this higher-risk population.

Implementation of Prevention Science to Eliminate Health Care Inequities in Achieving Cardiovascular Health: A Scientific Statement From the American Heart Association.

Prevention of cardiovascular and related diseases is foundational to attaining ideal cardiovascular health to improve the overall health and well-being of individuals and communities. Social determinants of health and health care inequities adversely affect ideal cardiovascular health and prevention of disease. Achieving optimal cardiovascular health in an effective and equitable manner requires a coordinated multidisciplinary and multilayered approach. In this scientific statement, we examine barriers to ideal cardiovascular health and its related conditions in the context of leveraging existing resources to reduce health care inequities and to optimize the delivery of preventive cardiovascular care. We systematically discuss (1) interventions across health care environments involving direct patient care, (2) leveraging health care technology, (3) optimizing multispecialty/multiprofession collaborations and interventions, (4) engaging local communities, and (5) improving the community environment through health-related government policies, all with a focus on making ideal cardiovascular health equitable for all individuals.

Optimizing Dietary Patterns and Lifestyle to Reduce Atherosclerotic Cardiovascular Risk Among South Asian Individuals.

South Asians are at an elevated risk of atherosclerotic cardiovascular disease (ASCVD) when compared with other age-matched subjects of varied ethnicities. The elevated ASCVD risk is multifactorial including a constellation of hypertension, dyslipidemia, metabolic syndrome, overweight/obesity, prediabetes, and type 2 diabetes mellitus. Although traditional ASCVD risk factors remain highly prevalent in South Asians living in the United States, modifiable risk factors of diet, lack of physical activity/increased sedentary time, smoking (of all forms), and excessive alcohol consumption further accelerate the disease process. In this review, we take a deep dive into optimizing lifestyle to reduce the risk of cardiovascular disease in this high-risk ethnic group.

Dyslipidemia in Human Immunodeficiency Virus Disease: JACC Review Topic of the Week.

The advent of newer and better tolerated antiretroviral therapy has progressively shortened the life expectancy gap between people living with HIV (PWH) and the general population. However, in this aging cohort, cardiovascular disease is now a significant cause of morbidity and mortality despite advances in cardiac care. Therefore, it is critical to assess and treat all cardiovascular disease risk factors, including dyslipidemia, early and aggressively in PWH. Data are not as robust regarding the pathogenesis and management of dyslipidemia in PWH, with most evidence being extrapolated from the general uninfected population. In this review the authors describe the current understanding of the pathophysiology of HIV and antiretroviral therapy-induced dyslipidemia, and the approach to risk assessment and management, given that drug-drug interactions remain an important consideration in this population.

Bempedoic Acid: A Contemporary Review of Its Pharmacology, Efficacy, and Safety Profile, Including Recent Data from the CLEAR Outcomes Clinical Trial.

PURPOSE OF REVIEW: To provide an updated review of bempedoic acid's clinical application in lowering LDL-C in the setting of statin intolerance and the recent findings in the CLEAR Outcomes trial as well as summarize and synthesize the current state of knowledge regarding bempedoic acid while providing an in-depth analysis of the drug's pharmacological properties, mechanism of action, clinical trials, safety, and efficacy. RECENT FINDINGS: The CLEAR Outcomes trial has provided evidence to support bempedoic acid as a viable alternative to statins for the primary and secondary prevention of cardiovascular disease. Bempedoic acid is a promising treatment option for patients with hypercholesterolemia who are unable to tolerate statin therapy or require additional LDL-C reduction in the treatment of cardiovascular disease, with the newest lipid-lowering cardiovascular outcomes trials expanding on their generalizability particularly in the inclusion of women.

Leveling the playing field: The utility of coronary artery calcium scoring in cardiovascular risk stratification in South Asians.

South Asian (SA) individuals, particularly those that reside in the United States and other Westernized countries, are at an elevated risk for ASCVD and mortality related to ASCVD. The 2018 ACC/AHA/Multi-society Cholesterol guideline listed SA as a high-risk ethnicity, underscoring the importance of treating modifiable risk factors to reduce ASCVD burden. Coronary artery calcium (CAC), a highly specific marker of subclinical atherosclerosis, may be a useful test to improve risk stratification among SA individuals. CAC testing is a cost-effective, highly reproducible, and specific marker of subclinical atherosclerosis, shown to improve ASCVD risk assessment across all racial/ethnic groups, thereby serving as a guide for initiating or deferring preventive therapies. In this White Paper we will discuss the use of CAC scoring to optimize risk stratification and delivery of preventive therapies to individuals of SA ethnicity.

Primary Prevention Management of Elevated Lipoprotein(a).

A male individual in his 40s with a strong family history of atherosclerotic cardiovascular disease including premature cardiovascular events in multiple family members presents to your clinic to establish care for cardiovascular risk stratification. What would you do next?

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors. OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH. METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and sex-stratified analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension, and current smoking. RESULTS: Among the cohort, 98/280 men (35%) and 89/502 women (18%) had premature ASCVD (defined as <55 years in men and <65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p=<0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005). CONCLUSION: These data confirm that high percentages of women and men with FH develop premature ASCVD, and suggest that FH may narrow the observed sex difference in premature ASCVD onset. These data support more aggressive prevention and treatment strategies in FH, including in women, to reduce non-lipid risk factors and residual hypercholesterolemia.