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?

Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo.

Importance: Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported. Objective: To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation. Design, Setting, and Participants: Men 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022. Interventions: Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up. Main Outcomes and Measures: Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome). Results: Statins were initiated by 1033 vitamin D-assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D-assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin-D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%). Conclusions and Relevance: Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels. Trial Registration: ClinicalTrials.gov Identifier: NCT01169259.

Guidelines for the management of hyperlipidemia: How can clinicians effectively implement them?

Guidelines support lowering cholesterol to decrease atherosclerotic cardiovascular disease (ASCVD) risk across the entire lifespan with intensive lifestyle intervention, as well as statin and non-statin pharmacotherapy for those at highest risk. Modest improvements in the initiation, use, and adherence to statin therapy in patients with ASCVD have occurred over the past decades. However, studies continue to document a less than desired implementation of guidelines highlighting a substantial and persistent treatment gap. The success of implementation depends on the consideration of a variety of barriers that exist throughout the healthcare delivery system. Further research is needed to comprehensively evaluate these barriers in order to develop appropriate and sustainable interventions to improve guideline implementation.

Statin Usage in Primary Prevention-Comparing the USPSTF Recommendations With the AHA/ACC/Multisociety Guidelines.

This Editorial compares the US Preventive Services Task Force (USPSTF) recommendations with the American Heart Association/American College of Cardiology (AHA/ACC)/multisociety guidelines on statin usage in primary prevention.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey.

INTRODUCTION: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. RESULTS: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. CONCLUSION: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

Inter-Individual Variability in Lipid Response: A Narrative Review.

Lipid-lowering guidelines emphasize shared decision-making between clinicians and patients, resulting in patients anticipating the degree of response from diet or drug therapy. Challenging for physicians is understanding the sources of variability complicating their management decisions, which include non-adherence, genetic considerations, additional lipid parameters including lipoprotein (a) levels, and rare systemic responses limiting benefits that result in non-responsiveness to monoclonal antibody injection. In this narrative review, we focus on the variability of low-density lipoprotein cholesterol (LDL-C) response to guideline-directed interventions such as statins, ezetimibe, bile acid sequestrants, fibrates, proprotein/convertase subtilisin-kexin type 9 inhibitors, and LDL-C-lowering diets. We hypothesize that the variability in individual lipid responses is multifactorial. We provide an illustrative model with a check list that can be used to identify factors that may be present in the individual patient.

Statin-associated muscle symptoms in the VITamin D and OmegA-3 TriaL (VITAL).

Statins are highly effective medications that reduce risk of atherosclerotic cardiovascular disease, but are very commonly discontinued by patients because of muscle symptoms. The risk factors for statin-associated muscle symptoms (SAMS) are not well understood, so in this study we examined the predictors of SAMS in a well-studied cohort of patients in the VITAL trial. We found that female sex and younger age (50-64 years) were significant, independent predictors of higher rates of SAMS.

Managing Atherosclerotic Cardiovascular Risk in Young Adults: JACC State-of-the-Art Review.

There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in the 20- to 39-year age range (young adults). These include tobacco use, elevated blood pressure/hypertension, family history of premature ASCVD, primary severe hypercholesterolemia such as familial hypercholesterolemia, diabetes with diabetes-specific risk-enhancing factors, or the presence of multiple other risk-enhancing factors, including in females, a history of pre-eclampsia or menopause under age 40. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a) that are useful in understanding an individual's long-term ASCVD risk. The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, that have potential clinical utility, but whose best use remains uncertain. Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood.

Eruptive Xanthomas: Importance of Recognition to Reduce Delay of Effective Triglyceride Reduction.

Eruptive xanthomas are localized lipid deposits in the dermis and an important early clue to severe hypertriglyceridemia. These small erythematous or yellow papules that localize to the extensor surfaces of extremities, buttocks, and the back are often overlooked during routine visits secondary to poor familiarity and limited skin examinations. We present 3 cases of patients with eruptive xanthomas and severe hypertriglyceridemia who underwent skin biopsy and waited weeks to years before receiving effective treatment. We suggest the following to minimize the delay between presentation and effective management. First, perform a comprehensive skin examination. Second, be mindful of the association between metabolic syndrome or diabetes with severe hypertriglyceridemia. Third, evaluate the Four D's of secondary hypertriglyceridemia: Diet/Lifestyle, Drugs/Medications, and Diseases/Disorders of metabolism. Finally, initiate effective treatment promptly after recognition. This includes beginning with a minimal fat diet and appropriate pharmacological intervention to control triglycerides as outlined in recent guidelines.

Facility-Level Variation in Reported Statin-Associated Side Effects Among Patients with Atherosclerotic Cardiovascular Disease-Perspective from the Veterans Affair Healthcare System.

PURPOSE: Statin-associated side effects (SASEs) can limit statin adherence and present a potential barrier to optimal statin utilization. How standardized reporting of SASEs varies across medical facilities has not been well characterized. METHODS: We assessed facility-level variation in SASE reporting among patients with atherosclerotic cardiovascular disease receiving care across the Veterans Affairs (VA) healthcare system from October 1, 2014, to September 30, 2015. The facility rates for SASE reporting were expressed as cases per 1000 patients with ASCVD. Facility-level variation was determined using hierarchical regression analysis to calculate median rate ratios (MRR [95% confidence interval]) by first using an unadjusted model and then adjusting for patient, provider, and facility characteristics. RESULTS: Of the 1,248,158 patients with ASCVD included in our study across 130 facilities, 13.7% had at least one SASE reported. Individuals with a history of SASE were less likely to be on a statin at follow-up compared with those without SASE (72.0% vs 80.8%, p < 0.01). The median (interquartile range) facility rate of SASE reported was 140.5 (109.4-167.7) cases per 1000 patients with ASCVD. Significant facility-level variation in the rate of SASE reported was observed: MRR 1.38 (1.33-1.44) in the unadjusted model and MRR 1.56 (1.47-1.65) in the adjusted model. CONCLUSION: Significant facility-level variation in SASE reporting was found within the VA healthcare system suggesting room for improvement in standardized documentation of SASEs among medical facilities. This has the potential to lead to improvement in statin utilization.

Shared decision making and patient reported outcomes among adults with atherosclerotic cardiovascular disease, medical expenditure panel survey 2006-2015.

IMPORTANCE: Shared decision-making (SDM), one of the pillars of patient centered care is strongly encouraged and has been incorporated into the management of atherosclerotic cardiovascular disease (ASCVD) but the expansion of its use has been limited. OBJECTIVE: To determine the association of SDM on patient-reported health status, measures of quality of care, healthcare resource utilization, and healthcare spending among US adults with ASCVD. METHOD: This is a retrospective cohort study in an ambulatory setting, utilizing the Medical Expenditure Panel Survey (MEPS) 2006-2015. Analysis completed in December 2020. Participants included were adults 18 years and over with a diagnosis of ASCVD. We used the average weighted response to self-administered questionnaire evaluating shared-decision-making process as the exposure variable in the regression model. Outcome measures included inpatient hospitalizations, Emergency Department (ED) visits, statin and aspirin use, self-perception of health, and healthcare expenditure. RESULTS: When compared with individuals reporting poor SDM, those with optimal SDM were more likely to report statin and aspirin use [statin use, Odds Ratio (OR) 1.26 (95% CI, 1.09-1.46)], [aspirin use, 1.25 (1.07-1.45)], more likely to have a positive perception of their health and healthcare related quality of life, and were less likely to visit the ED [OR for ≥ 2 ED visits: 0.81 (0.67-0.99)]. There was no difference between groups in annual total or out of pocket healthcare expenditure. CONCLUSION: This study suggests that effective SDM is associated with better utilization of healthcare resources and patient reported health outcomes. We hope these results could provide useful evidence for expanding the use of SDM in patient-centered care among individuals with ASCVD.

Association of patient, provider and facility related characteristics with statin associated side effects and statin use: Insight from the Veteran's Affairs healthcare system.

BACKGROUND: Statin associated side effects (SASE) are a leading cause of statin discontinuation. OBJECTIVE: We evaluated patient, provider, and facility characteristics associated with SASEs and whether these characteristics impact statin utilization. METHODS: Patients with atherosclerotic cardiovascular disease (ASCVD) receiving care across the Veterans Affairs healthcare system from October 1, 2014 to September 30, 2015 were included. Multivariable logistic regression analyses were performed to determine (a) factors associated with SASE and (b) factors associated with statin use in those with SASE. RESULTS: Our cohort included 1,225,576 patients with ASCVD. Of these, 171,189 (13.7%) had at least 1 reported SASE since year 2000. The most significant odds for SASEs were observed with female sex (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.36, 1.45), White race (OR 1.43, 95% CI 1.41, 1.45), hypertension (OR 1.37, 95% CI 1.33, 1.41) and ischemic heart disease (IHD: OR 1.45, 95% CI 1.43, 1.47). Lower odds were noted with care at a teaching facility (OR 0.89, 95% CI 0.88, 0.90). Factors most associated with being on a statin among patients with SASE included having diabetes (OR 1.18, 95% CI 1.15, 1.20), IHD (OR 1.39, 95% CI 1.35, 1.43) and a higher number of cardiology visits (OR 1.08, 95% CI 1.07, 1.09), while female sex was associated with lower odds (OR 0.65, 95% CI 0.61, 0.69). CONCLUSION: There are significant disparities in statin use by sex, ASCVD type, and comorbidities among secondary prevention patients with SASE, which represent areas for improvement in optimizing statin utilization.