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.

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.

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.

A possible mechanism of hyperlipidemia in a patient with metastatic non-small cell lung cancer on lorlatinib therapy.

INTRODUCTION: We report the case of a woman who developed hyperlipidemia on lorlatinib therapy found to have minimal change disease. We review therapies for cancer known to alter the lipid profile, in addition to reviewing secondary hyperlipidemia workup. We also propose a mechanism for lorlatinib-induced hyperlipidemia. CASE REPORT: A 63 year old woman with non-small cell lung adenocarcinoma on lorlatinib therapy develops marked hyperlipidemia.Management & outcome: A secondary hyperlipidemia workup is performed which reveals nephrotic range proteinuria. Minimal change disease is found on renal biopsy. The hyperlipidemia was initially responsive to statin therapy, then required addition of ezetimibe. DISCUSSION: This is a case of hyperlipidemia in a patient on lorlatinib. The case highlights that therapies for lung cancer and other malignancies have the potential to alter the lipid profile. We propose minimal change disease as a possible mechanism for lorlatinib-induced dyslipidemia. Additionally, we discuss the crucial aspects of secondary hyperlipidemia workup.

Nondietary Cardiovascular Health Metrics With Patient Experience and Loss of Productivity Among US Adults Without Cardiovascular Disease: The Medical Expenditure Panel Survey 2006 to 2015.

Background The American Heart Association 2020 Impact Goals aimed to promote population health through emphasis on cardiovascular health (CVH). We examined the association between nondietary CVH metrics and patient-reported outcomes among a nationally representative sample of US adults without cardiovascular disease. Methods and Results We included adults aged ≥18 years who participated in the Medical Expenditure Panel Survey between 2006 and 2015. CVH metrics were scored 1 point for each of the following: not smoking, being physically active, normal body mass index, no hypertension, no diabetes mellitus, and no dyslipidemia, or 0 points if otherwise. Diet was not assessed in Medical Expenditure Panel Survey. Patient-reported outcomes were obtained by telephone survey and included questions pertaining to patient experience and health-related quality of life. Regression models were used to compare patient-reported outcomes based on CVH, adjusting for sociodemographic factors and comorbidities. There were 177 421 Medical Expenditure Panel Survey participants (mean age, 45 [17] years) representing ~187 million US adults without cardiovascular disease. About 12% (~21 million US adults) had poor CVH. Compared with individuals with optimal CVH, those with poor CVH had higher odds of reporting poor patient-provider communication (odds ratio, 1.14; 95% CI, 1.05-1.24), poor healthcare satisfaction (odds ratio, 1.15; 95% CI, 1.08-1.22), poor perception of health (odds ratio, 5.89; 95% CI, 5.35-6.49), at least 2 disability days off work (odds ratio, 1.39; 95% CI, 1.30-1.48), and lower health-related quality of life scores. Conclusions Among US adults without cardiovascular disease, meeting a lower number of ideal CVH metrics is associated with poor patient-reported healthcare experience, poor perception of health, and lower health-related quality of life. Preventive measures aimed at optimizing ideal CVH metrics may improve patient-reported outcomes among this population.

Perspective: Childhood Obesity Requires New Strategies for Prevention.

The prevalence of obesity among youth in the USA is currently >18% with projections that more than half of today's children will be obese as adults. The growth trajectory of children more likely to become obese is determined by weight in earliest childhood, and childhood body mass index (BMI) tracks through adolescence and adulthood. Childhood consequences of obesity include increased risk of asthma, type 2 diabetes mellitus, orthopedic disorders, and reduced academic performance. Health implications of obesity in adulthood include premature coronary artery disease, hypertension, type 2 diabetes, stroke, and certain cancers, contributing to the leading causes of adult mortality. Early childhood obesity is influenced by prenatal exposure to maternal obesity and environmental obesogens, and is associated with poverty, food insecurity, and poor nutritional quality. New strategies for primordial prevention of early childhood obesity require focusing attention on growth parameters during the first 2 y of life, with support for increasing the duration of breastfeeding, and improvements in dietary quality and availability, particularly the reduced consumption of added sugars. Reducing the prevalence of obesity among adolescent females and reducing exposure to environmental obesogens may reduce the prevalence of transgenerational obesity. The reduction of early childhood obesity could improve population health, quality of life, and longevity throughout the life course.

JCL roundtable. The 2018 AHA/ACC/Multisociety Cholesterol Guidelines: Process and product.

In this NLA Roundtable four members of the writing committee join the Editor to discuss the process of developing the AHA/ACC/Multisociety Cholesterol Guidelines, which were unveiled in November 2018. They also provide personal insights on the finished product. Highlights include 1) the committee's decision to summarize 10 take-home messages providing rapid communication of key points, 2) emphasis on clinician -patient discussion, which may bring up issues specific to women or other population groups at risk, 3) personalizing risk with risk-enhancing factors such as LDL-C ≥ 160 mg/dl, metabolic syndrome, chronic kidney disease, pre-eclampsia, premature menopause, high risk ethnicity, inflammatory diseases, hypertriglyceridemia and in selected cases, Lp(a), hs-CRP and apoB; 4) using coronary artery calcium scoring when a risk decision is uncertain in intermediate risk patients 5) monitoring for goals of moderate or intensive LDL cholesterol reduction, 6) thresholds for adding nonstatin LDL-lowering therapy in those at very high risk or for heterozygous familial hypercholesterolemia and 7) cost value assessment for expensive treatment.

Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention: A Review Part 2.

Efforts to better control risk factors for cardiovascular disease and prevent the development of subsequent cardiovascular events are crucial to maintaining healthy populations. In today's busy practice environment and with the overwhelming pace of new research findings, ensuring appropriate emphasis and implementation of evidence-based preventive cardiovascular care can be challenging. The ABCDEF approach to cardiovascular disease prevention is intended to improve dissemination of contemporary best practices and ease the implementation of comprehensive preventive strategies for clinicians. This review serves as a succinct yet authoritative overview for interested internists as well as for cardiologists not otherwise focused on cardiovascular disease prevention. The goal of this 2-part series is to compile a state-of-the-art list of elements central to primary and secondary prevention of cardiovascular disease, using an ABCDEF checklist. In Part 2, we review new recommendations about lipid-modifying strategies, contemporary best practice for tobacco cessation, new evidence related to cardiovascular risk reduction in diabetes using novel therapies, ways to implement a heart-healthy diet, modern interventions to improve physical exercise, and how best to prevent the onset of heart failure.

Differences in statin utilization and lipid lowering by race, ethnicity, and HIV status in a real-world cohort of persons with human immunodeficiency virus and uninfected persons.

BACKGROUND: Risks for cardiovascular diseases, including myocardial infarction and stroke, are elevated in people with HIV infection (PWH). However, no trials of statin utilization with clinical cardiovascular disease (CVD) end points have been completed in PWH, and there are sparse real-world data regarding statin use and lipid-lowering effectiveness. We therefore used a unique cohort of PWH and uninfected controls to evaluate (1) differences in statin types used for PWH versus uninfected persons; (2) lipid lowering achieved by statin use for PWH versus uninfected persons; and (3) racial and ethnic disparities in appropriate statin use among PWH and uninfected persons. METHODS: We analyzed a cohort of 5,039 PWH and 10,011 uninfected demographically matched controls who received care at a large urban medical center between January 1, 2000, and May 17, 2017. Medication administration records, prescription data, and validated natural language processing algorithms were used to determine statin utilization. Statins were categorized by generic active ingredient name and intensity (high, moderate, or low). Lipid values collected in routine clinical care were available for analysis. The first set of analyses was restricted to PWH and uninfected matched controls taking statins and compared (1) differences in statin type and (2) difference in cholesterol levels after versus before statin initiation by HIV status. For the second set of analyses, we first used prevalent CVD risk factors to determine participants with statin indications and then determined how many of these participants were taking statins. We then compared statin utilization among persons with indications for statins by race/ethnic group for PWH and uninfected matched controls using multivariable-adjusted logistic regression. RESULTS: Among people prescribed statins, PWH were more likely than controls to have ever taken pravastatin (34.8% vs 12.3%, P < .001) or atorvastatin (72.2% vs 65.6%, P = .002) and less likely to have ever taken simvastatin (14.2% vs 39.5%, P < .001). Among PWH with indications for statin utilization, 55.7% of whites, 39.4% of blacks, and 45.8% of Hispanics were prescribed statins (P < .001). These differences in statin prescription by race/ethnicity remained significant after adjustment for demographics (including insurance status), cardiovascular risk factors, antiretroviral therapy use, HIV viremia, and CD4 count. These racial/ethnic disparities in statin utilization were less pronounced among uninfected persons. CONCLUSIONS: Among PWH with statin indication(s), blacks and Hispanics were less likely than whites to have been prescribed a statin. These racial/ethnic disparities were less pronounced among uninfected persons. There were significant differences in type of statin used for PWH compared to uninfected matched controls. Future efforts addressing disparities in CVD prevention among PWH are warranted.

Lipids and Women's Health: Recent Updates and Implications for Practice.

The obstetrician/gynecologist frequently serves as the primary care physician for women. Specialty-specific guidelines vary in screening recommendations for lipid disorders; women's health practitioners often follow recommendations to screen at age 45 in the absence of other risk factors. However, 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend screening at age 21 to capture those at risk of cardiovascular disease and allow for early intervention with lifestyle and, in the most severe cases, evidence-based statins. We discuss the care of women who primarily benefit from screening: those with familial hypercholesterolemia (FH), those with the metabolic syndrome (MetS) or polycystic ovary syndrome, and those with hypertriglyceridemia. Those with FH have elevated low-density lipoprotein cholesterol from birth and a propensity for premature coronary heart disease. Early recognition of FH can allow risk-reducing interventions, as well as identification of additional affected relatives. Early detection of metabolic variables, such as in the MetS and hypertriglyceridemia, can lead to an enhanced focus on physical activity and heart-healthy diet. Finally, we discuss a practical approach to lipid management and review concerns regarding drug safety. Our objective is to provide a current overview of cardiovascular risk factor optimization that women's health practitioners can use in identifying and/or treating patients at risk for cardiovascular disease and diabetes.

Statins for Primary Prevention in Older Adults-Moving Toward Evidence-Based Decision-Making.

OBJECTIVES: To determine the efficacy and safety of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) events in older adults, especially those aged 80 and older and with multimorbidity. METHODS: The National Institute on Aging and the National Heart, Lung and Blood Institute convened A multidisciplinary expert panel from July 31 to August 1, 2017, to review existing evidence, identify knowledge gaps, and consider whether statin safety and efficacy data in persons aged 75 and older without ASCVD are sufficient; whether existing data can inform the feasibility, design, and implementation of future statin trials in older adults; and clinical trial options and designs to address knowledge gaps. This article summarizes the presentations and discussions at that workshop. RESULTS: There is insufficient evidence regarding the benefits and harms of statins in older adults, especially those with concomitant frailty, polypharmacy, comorbidities, and cognitive impairment; a lack of tools to assess ASCVD risk in those aged 80 and older; and a paucity of evidence of the effect of statins on outcomes of importance to older adults, such as statin-associated muscle symptoms, cognitive function, and incident diabetes mellitus. Prospective, traditional, placebo-controlled, randomized clinical trials (RCTs) and pragmatic RCTs seem to be suitable options to address these critical knowledge gaps. Future trials have to consider greater representation of very old adults, women, underrepresented minorities, and individuals of differing health, cognitive, socioeconomic, and educational backgrounds. Feasibility analyses from existing large healthcare networks confirm appropriate power for death and cardiovascular outcomes for future RCTs in this area. CONCLUSION: Existing data cannot address uncertainties about the benefits and harms of statins for primary ASCVD prevention in adults aged 75 and older, especially those with comorbidities, frailty, and cognitive impairment. Evidence from 1 or more RCTs could address these important knowledge gaps to inform person-centered decision-making. J Am Geriatr Soc 66:2188-2196, 2018.

Statin therapy across the lifespan: evidence in major age groups.

This review provides needed perspective on statin efficacy and safety in individuals under 40, 40-75, and > 75 years of age. Starting with the 2013 ACC-AHA cholesterol guidelines extensive evidence base on randomized controlled trials (RCTs) we added references in the past 5 years that discussed statin efficacy and safety over the life span. In those under 40, statins are primarily used for treatment of severe hypercholesterolemia, often familial, and they are well tolerated. In middle-aged adults, statins have strong evidence for benefit in primary and secondary prevention trials; however, in primary prevention, a clinician-patient risk discussion should precede statin prescription in order to determine appropriate treatment. In those over 75, issues of statin intensity and net benefit loom large as associated comorbidity, polypharmacy, and potential for adverse effects impact the decision to use statins with RCT data strongest in support of use in secondary prevention. Statin drugs have been studied by RCTs in a large number of individuals. In those groups shown to benefit, statins have reduced the risk of atherosclerotic cardiovascular disease with few side effects as compared to controls. This review has detailed considerations that should occur when statins are given to individuals in different age groups.

Statin Use and Aneurysm Risk in Patients With Bicuspid Aortic Valve Disease.

BACKGROUND: No medical therapy has been proven to prevent the progression of aortic dilatation in bicuspid aortic valve (BAV) disease, and prophylactic aortic surgery remains the mainstay of treatment. HYPOTHESIS: Among patients with BAV disease who are referred for surgery, preoperative statin use is associated with decreased odds of ascending aortic dilatation. METHODS: We reviewed all BAV patients who underwent aortic valve and/or aortic surgery at our center between April 2004 and December 2013. Aortic diameter (AD), defined as the maximum ascending aortic dimension, was determined by magnetic resonance imaging, computed tomography, or echocardiography. Patients were divided into 2 groups: maximal AD <4.5 cm or ≥4.5 cm. The association between preoperative statin use and aortic dilatation was assessed using multivariable logistic regression modeling. RESULTS: Of 680 consecutive patients, 405 (60%) had AD <4.5 cm (mean age, 60 ± 14 years; 45% on statins), whereas 275 (40%) had AD ≥4.5 cm (mean age, 54 ± 13 years; 35% on statins) at the time of surgery. After adjusting for age, body surface area, sex, hypertension, aortic stenosis, severity of aortic regurgitation, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers, patients with AD ≥4.5 cm had 0.66× lower odds (95% confidence interval: 0.45-0.96) of being on preoperative statins compared with those with AD <4.5 cm (P = 0.029). CONCLUSIONS: In a retrospective study of BAV patients referred for surgery, preoperative statin use was associated with lower odds of clinically significant ascending aortic dilatation.

Familial Hypercholesterolemia and the 2013 American College of Cardiology/American Heart Association Guidelines: Myths, Oversimplification, and Misinterpretation Versus Facts.

Familial hypercholesterolemia (FH) is a genetic condition resulting in severe, lifelong elevations in low-density lipoprotein cholesterol and a marked increased risk of early-onset coronary disease. FH is treatable when identified, yet is vastly under-recognized and undertreated. Although the 2013 American College of Cardiology/American Heart Association guidelines on the treatment of cholesterol presented a paradigm shift, we believe that there have been serious oversimplifications, misinterpretations, and erroneous reporting about the current ACC/AHA cholesterol guidelines that have contributed to suboptimal care for these subjects. In summary, the ACC/AHA guidelines place tremendous emphasis on the identification of patients with FH, the initiation of high-intensity statin therapy, the need to obtain follow-up lipid values to assess the efficacy and compliance to lifestyle and medical therapy, and the role of nonstatin drugs when needed for optimal care of the individual patient.

Addressing statin adverse effects in the clinic: the 5 Ms.

With the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, emphasis has been placed on using evidence-based intensity of therapy to reduce atherosclerotic cardiovascular disease (ASCVD) risk, rather than focusing on goal cholesterol levels. Before initiating therapy, however, it is critical that physicians and patients discuss 4 key topics: (1) the benefit of ASCVD risk reduction, (2) medication adverse effects, (3) drug-drug interactions, and (4) patient preferences. To facilitate discussion of statin adverse effects, we present here an evidence-based review of the 5 Ms of statin adverse effects: metabolism, muscle, medication interactions, major organ effects, and memory. "Metabolism" represents the small risk of new-onset diabetes that comes with statins, which is highest in those with diabetes risk factors. "Muscle" requires discussion of the wide range of muscle symptoms that occur with statins but emphasizes that these have been no more prevalent than those experienced with placebo in randomized controlled trials (RCTs). "Medication interactions" emphasize that statins interact with numerous medications. Interaction profiles vary widely between statins, and patients should be made aware of the most common interactions with their prescription. "Major organ effects" prompt the physician to review the possibility of a transient transaminitis as well as the recent observation of rare acute kidney injury with statin use. Both are rare and do not require routine monitoring. Finally, "memory" references the recent observational data suggesting statins may contribute to memory loss and confusion, both of which have not been observed in RCTs and resolve with drug cessation. Reviewing these common effects has the possibility to strengthen the doctor-patient relationship and boost both medication adherence and patient satisfaction.