Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association.

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.

Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.

Effects of low dose versus high dose human growth hormone on body composition and lipids in adults with GH deficiency: a meta-analysis of placebo-controlled randomized trials.

PURPOSE: Doses of growth hormone in adults with growth hormone deficiency are now lower than previously. However, it is not clear they are as effective as higher doses. The objective of this meta-analysis was to assess efficacy of low to moderate dose (LD) GH replacement on standard endpoints of GH compared to higher doses. METHODS: A meta-analysis was carried out using PubMed, Cochrane and Embase databases from 1960 to 9/23/12. Three reviewers identified randomized double-blind, placebo-controlled trials of 6 months duration. Of 173 publications, 28 representing 22 trials (591 GH-treated patients and 562 placebo) were included. Data were independently extracted by three reviewers. Endpoints were analyzed if ≥4 studies per dose group reported baseline and 6 month data. RESULTS: Mean lean body mass (LBM) increased by 2.61 kg in GH-treated subjects versus 0.04 in the placebo group (P < 0.0001). Fat mass (FM) was reduced by -2.19 kg versus 0.31 (GH vs. placebo) (P = 0.0002). Changes in LBM and FM were dose-related (P = 0.02 and 0.007, respectively), high dose (HD) being more effective than low dose (LBM P = 0.03 and FM P = 0.04). In contrast, treatment with GH reduced total cholesterol -0.38 mmol/L versus. 0.01 (placebo) (P < 0.0001), and low density lipoprotein cholesterol (LDL-C) -0.42 mmol/L versus -0.1 (P = 0.0009), but there were no differences between LD and HD GH. CONCLUSIONS: LDs of hGH improve total- and LDL-C, and body composition. Higher doses are more effective on body composition, but not lipids.

Reflecting on Progress in and Establishing Benchmarks for Sex and Gender Health Education.

ABSTRACT: Sex and gender influence every aspect of human health; thus, sex- and gender-related topics should be incorporated in all aspects of health education curricula. Sex and gender health education (SGHE) is the rigorous, intersectional, data-driven integration of sex and gender into all elements of health education. A multisectoral group of thought leaders has collaborated to advance SGHE since 2012. This cross-sector collaboration to advance SGHE has been successful on several fronts, primarily developing robust interprofessional SGHE programs, hosting a series of international SGHE summits, developing sex- and gender-specific resources, and broadening the collaboration beyond medical education. However, other deeply entrenched challenges have proven more difficult to address, including accurate and consistent sex and gender reporting in research publications, broadening institutional support for SGHE, and the development and implementation of evaluation plans for assessing learner outcomes and the downstream effects of SGHE on patient care. This commentary reflects on progress made in SGHE over the first decade of the current collaboration (2012-2022), articulates a vision for next steps to advance SGHE, and proposes 4 benchmarks to guide the next decade of SGHE: (1) integrate sex, gender, and intersectionality across health curricula; (2) develop sex- and gender-specific resources for health professionals; (3) improve sex and gender reporting in research publications; and (4) develop evaluation plans to assess learner and patient outcomes.

Effects of endocrine disorders on lipids and lipoproteins.

Endocrine diseases may be associated with dyslipidaemia and may increase atherosclerotic cardiovascular disease (ASCVD) risk. This chapter describes changes in lipids and lipoproteins in diseases of the pituitary, thyroid, adrenal glands, ovaries, and testes, the mechanisms for these changes, ASCVD risk in these endocrine disorders, and whether treatment of the endocrine disorder improves the lipid profile and reduces ASCVD risk. Acromegaly, GH deficiency, Cushing syndrome, chronic glucocorticoid replacement, hypothyroidism, PCOS and male hypogonadism can increase LDL-C and/or TG. Marked reductions in LDL-C are associated with hyperthyroidism, and extremely low HDL-C levels with testosterone and/or other anabolic steroid abuse. Acromegaly, GH deficiency, Cushing syndrome, and chronic glucocorticoid replacement are associated with increased ASCVD risk. Treatment of acromegaly, GH deficiency, hypothyroidism, Cushing syndrome, and testosterone deficiency reduce LDL-C, although statin therapy may still be needed. Effects on ASCVD are not known.

Targeting PCSK9 With Antibodies and Gene Silencing to Reduce LDL Cholesterol.

The discovery of PCSK9 and its role in regulating the low-density lipoprotein (LDL) receptor, and the effect of loss-of-function mutations of its gene, identified it as a therapeutic target in 2006. Fully humanized monoclonal antibodies to PCSK9 (alirocumab and evolocumab) proved effective for lowering LDL cholesterol and subsequently for reducing atherosclerotic events in large outcome trials. Suppressing PCSK9 synthesis via gene silencing using inclisiran, a small interfering RNA, is another approach that effectively reduces LDL cholesterol, and a cardiovascular outcome trial is in progress. These treatments are given subcutaneously on a background of maximally tolerated statin treatment and are long-lasting: dosing is once or twice a month, self-administered, for alirocumab and evolocumab, and every 6 months for inclisiran, in the clinic, with an extra dose at 3 months in the initial year of therapy. These 3 agents produce mean LDL reductions of about 55% with no important adverse effects detectable to date. They are indicated in patients with atherosclerotic vascular disease or familial hypercholesterolemia who cannot achieve LDL cholesterol targets with maximally tolerated statin treatment. Such therapy can produce very low plasma LDL cholesterol and PCSK9, but there is no evidence this is harmful. Introduction into clinical practice has been impeded by economic considerations. The barrier to their use has not been scientific or medical, but rather the impact on healthcare resources. Prices have been reduced, but whether they are now cost-effective varies from country to country.

Evidence-Based Dietary Practices to Improve Osteoarthritis Symptoms: An Umbrella Review.

While there is some research investigating whole foods or diets that are easily understood and accessible to patients with osteoarthritis, specific nutrients or nutraceuticals are more commonly identified. Unfortunately, guidelines and evidence surrounding individual nutrients, extracts, and nutraceuticals are conflicting and are more difficult to interpret and implement for patients with osteoarthritis. The purpose of this umbrella review is to provide a comprehensive understanding of the existing evidence of whole foods and dietary patterns effects on osteoarthritis-related outcomes to inform evidence-based recommendations for healthcare professionals and identify areas where more research is warranted. A literature search identified relevant systematic reviews/meta-analyses using five databases from inception to May 2022. Five systematic reviews/meta-analyses were included in the current umbrella review. Most evidence supported the Mediterranean diet improving osteoarthritis-related outcomes (e.g., pain, stiffness, inflammation, biomarkers of cartilage degeneration). There was little to no evidence supporting the effects of fruits and herbs on osteoarthritis-related outcomes; however, there was some suggestion that specific foods could potentiate symptom improvement through antioxidative mechanisms. The overall lack of homogeneity between the studies limits the conclusions that can be made and highlights the need for quality research that can identify consumer-accessible foods to improve osteoarthritis-related symptoms.

Preventing Osteoarthritis After an Anterior Cruciate Ligament Injury: An Osteoarthritis Action Alliance Consensus Statement.

After an anterior cruciate ligament (ACL) injury, people need secondary prevention strategies to identify osteoarthritis at its earliest stages so that interventions can be implemented to halt or slow the progression toward its long-term burden. The Osteoarthritis Action Alliance formed an interdisciplinary Secondary Prevention Task Group to develop a consensus on recommendations to provide clinicians with secondary prevention strategies that are intended to reduce the risk of osteoarthritis after a person has an ACL injury. The group achieved consensus on 15 out of 16 recommendations that address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. We hope this statement raises awareness among clinicians and researchers on the importance of taking steps to mitigate the risk of osteoarthritis after an ACL injury.

Evidence Review for Preventing Osteoarthritis After an Anterior Cruciate Ligament Injury: An Osteoarthritis Action Alliance Consensus Statement.

CONTEXT: The Osteoarthritis Action Alliance formed a secondary prevention task group to develop a consensus on secondary prevention recommendations to reduce the risk of osteoarthritis after a knee injury. OBJECTIVE: Our goal was to provide clinicians with secondary prevention recommendations that are intended to reduce the risk of osteoarthritis after a person has sustained an anterior cruciate ligament injury. Specifically, this manuscript describes our methods, literature reviews, and dissenting opinions to elaborate on the rationale for our recommendations and to identify critical gaps. DESIGN: Consensus process. SETTING: Virtual video conference calls and online voting. PATIENTS OR OTHER PARTICIPANTS: The Secondary Prevention Task Group consisted of 29 members from various clinical backgrounds. MAIN OUTCOME MEASURE(S): The group initially convened online in August 2020 to discuss the target population, goals, and key topics. After a second call, the task group divided into 9 subgroups to draft the recommendations and supportive text for crucial content areas. Twenty-one members completed 2 rounds of voting and revising the recommendations and supportive text between February and April 2021. A virtual meeting was held to review the wording of the recommendations and obtain final votes. We defined consensus as >80% of voting members supporting a proposed recommendation. RESULTS: The group achieved consensus on 15 of 16 recommendations. The recommendations address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. CONCLUSIONS: This consensus statement reflects information synthesized from an interdisciplinary group of experts based on the best available evidence from the literature or personal experience. We hope this document raises awareness among clinicians and researchers to take steps to mitigate the risk of osteoarthritis after an anterior cruciate ligament injury.

Safety of Statins and Nonstatins for Treatment of Dyslipidemia.

This article reviews the safety of statins and non-statin medications for management of dyslipidemia. Statins have uncommon serious adverse effects: myopathy/ rhabdomyolysis, which resolve with statin discontinuation, and diabetes, usually in people with risk factors for diabetes. The CVD benefit of statins far exceeds the risk of diabetes. Statin myalgia, without CK elevation, is likely caused by muscle symptoms with another etiology, or the nocebo effect. Notable adverse effects of non-statin medicines include injection site reactions (alirocumab, evolocumab, inclisiran), increased uric acid and gout (bempedoic acid), atrial fibrillation/flutter (omega-3-fatty acids), and myopathy in combination with a statin (gemfibrozil).

Exploring Obesity as a Gendered Contagion: Impact on Lifestyle Interventions to Improve Cardiovascular Health.

PURPOSE: Obesity increases the risk of cardiovascular disease. Lifestyle interventions such as physical activity and diet are important components for reducing the risk of obesity. Data suggest that lifestyle choices differ between men and women, as well as in groups. The purpose of this review was to explore whether obesity can be considered as a gendered social contagion, associated with differences in lifestyle and response to lifestyle interventions in men and women. FINDINGS: There are important sex-based differences of obesity to consider. There is evidence that peers have an influence on lifestyle preferences such as physical activity level and dietary habits, but the evidence is inconclusive if the differences exist between men and women. Similarly, data from lifestyle intervention studies are not conclusive whether there are differences between men and women. There is not enough evidence for the notion that obesity is a gendered social contagion. IMPLICATIONS: More research is needed to understand differences in lifestyle and lifestyle interventions between men and women, especially across the life span, which could have profound public health implications.

Mind the Gap: Exploring Nutritional Health Compared With Weight Management Interests of Individuals with Osteoarthritis.

Background: For persons with osteoarthritis (OA), nutrition education may facilitate weight and OA symptom management. Objectives: The primary aim of this study was to determine preferred OA-related nutritional and weight management topics and their preferred delivery modality. The secondary aim was to determine whether there is a disconnect between what patients want to know about nutrition and OA management and what information health-care professionals (HCPs) are providing to patients. Methods: The Osteoarthritis Action Alliance surveyed individuals with OA to identify their preferences, categorized in 4 domains: 1) strategies for weight management and a healthy lifestyle; 2) vitamins, minerals, and other supplements; 3) foods or nutrients that may reduce inflammation; and 4) diets for weight loss. HCPs were provided these domains and asked which topics they discussed with patients with OA. Both groups were asked to select currently utilized or preferred formats of nutritional resources. Results: Survey responses from 338 individuals with OA and 104 HCPs were included. The highest preference rankings in each domain were: 1) foods that make OA symptoms worse (65%), foods and nutrients to reduce inflammation (57%), and healthy weight loss (42%); 2) glucosamine (53%), vitamin D (49%), and omega-3 fatty acids (45%); 3) spices and herbs (65%), fruits and vegetables (58%), and nuts (40%); and 4) Mediterranean diet (21%), low-carbohydrate diet (18%), and fasting or intermittent fasting (15%). There was greater than 20% discrepancy between interests reported by individuals with OA and discussions reported by HCPs on: weight loss strategies, general information on vitamins and minerals, special dietary considerations for other conditions, mindful eating, controlling caloric intake or portion sizes, and what foods worsen OA symptoms. Most respondents preferred to receive nutrition information in a passive format and did not want information from social media messaging. Conclusions: There is disparity between the nutrition education content preferred by individuals with OA (which often lacks empirical support) and evidence-based topics being discussed by HCPs. HCPs must communicate evidence-based management of joint health and OA symptoms in patient-preferred formats. This study explored the information gap between what individuals with OA want to know and what HCPs believe they need to know.

Sex and Gender Health Educational Tenets: A Report from the 2020 Sex and Gender Health Education Summit.

Background: Sex as a biological variable and gender as a sociocultural variable influence many health conditions and outcomes. However, they have not been incorporated systematically into education across health professions. Methods: Areas of knowledge and abilities that apply to sex and gender education across health professions were summarized from the 2015 and 2018 Sex and Gender Health Education Summits. Results: Using this summary, draft tenets were developed by facilitated interprofessional discussion groups at the 2020 Summit, and then reviewed, edited, and refined by a writing group who recommended four tenets that health care professionals should be able to do: (1) demonstrate knowledge of sex and gender specific health (SGSH), (2) evaluate literature and the conduct of research for incorporation of sex and gender, (3) incorporate sex and gender considerations into clinical decision making, and (4) demonstrate patient advocacy with respect to sex and gender. Conclusion: These tenets provide the framework for collaborative interprofessional education about SGSH. Individual professions can also use the tenets to develop practice-specific competencies, competency statements, and/or assessment benchmarks within the structures of their respective accrediting bodies to advance the health of women, men, and sex and gender minority persons. Interprofessional collaborations are key for sharing best practices in development, curricular integration, and dissemination.

Mortality in COVID-19: Further Evidence for a Sex-Based Difference in the OpenSAFELY Study.

Although COVID-19 death rates are lower in women compared to men, it is not clear whether this difference in mortality is due to sex (biological) based factors, comorbidities that differ in men and women, or gender influences. New evidence supports a sex-based difference in COVID-19 mortality. Data from the OpenSAFELY cohort study in 17 million adult patients in England demonstrate that COVID-19-related deaths were associated with male sex (hazard ratio 1.59; 95% confidence interval 1.53-1.65) when fully adjusted for age, low income, smoking, pre-existing diseases, and ethnicity. Women have stronger innate and adaptive responses to infection. It is hypothesized that biological differences in the immune system may have a role in the sex-based difference in mortality from COVID-19. The results of OpenSAFELY demonstrate the importance of collection and analysis of sex-disaggregated data in research and public surveillance.

Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-analysis.

CONTEXT: Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. OBJECTIVE: The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018. STUDY SELECTION: Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. DATA EXTRACTION: Pairs of independent reviewers extracted data and appraised studies. DATA SYNTHESIS: Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. CONCLUSIONS: Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.

Weight Loss and Serum Lipids in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Excess adipose tissue is associated with an abnormal lipid profile that may improve with weight reduction. In this meta-analysis, we aimed to estimate the magnitude of change in lipid parameters associated with weight loss in adults who are overweight or obese. METHODS: We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus from 2013 to September, 2018. We included randomized controlled trials (RCTs) that evaluated interventions to treat adult obesity (lifestyle, pharmacologic and surgical) with follow-up of 6 months or more. RESULTS: We included 73 RCTs with moderate-to-low risk of bias, enrolling 32 496 patients (mean age, 48.1 years; weight, 101.6 kg; and body mass index [BMI], 36.3 kg/m2). Lifestyle interventions (diet, exercise, or both), pharmacotherapy, and bariatric surgery were associated with reduced triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) concentrations and increased high-density lipoprotein cholesterol (HDL-C) at 6 and 12 months. The following data are for changes in lipid parameters after 12 months of the intervention with 95% CI. Following lifestyle interventions, per 1 kg of weight lost, TGs were reduced by -4.0 mg/dL (95% CI, -5.24 to -2.77 mg/dL), LDL-C was reduced by -1.28 mg/dL (95% CI, -2.19 to -0.37 mg/dL), and HDL-C increased by 0.46 mg/dL (95% CI, 0.20 to 0.71 mg/dL). Following pharmacologic interventions, per 1 kg of weight lost, TGs were reduced by -1.25 mg/dL (95% CI, -2.94 to 0.43 mg/dL), LDL-C was reduced by -1.67 mg/dL (95% CI, -2.28 to -1.06 mg/dL), and HDL-C increased by 0.37 mg/dL (95% CI, 0.23 to 0.52 mg/dL). Following bariatric surgery, per 1 kg of weight lost, TGs were reduced by -2.47 mg/dL (95% CI, -3.14 to -1.80 mg/dL), LDL-C was reduced by -0.33 mg/dL (95% CI, -0.77 to 0.10 mg/dL), and HDL-C increased by 0.42 mg/dL (95% CI, 0.37 to 0.47 mg/dL). Low-carbohydrate diets resulted in reductions in TGs and increases in HDL-C, whereas low-fat diets resulted in reductions in TGs and LDL-C and increases in HDL-C. Results were consistent across malabsorptive and restrictive surgery. CONCLUSIONS: Weight loss in adults is associated with statistically significant changes in serum lipids. The reported magnitude of improvement can help in setting expectations, inform shared decision making, and facilitate counseling.

Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline.

OBJECTIVE: This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk. CONCLUSION: This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the endocrine disorder improves not only the lipid abnormalities, but also CV outcomes. Based on the available evidence, recommendations are made for the assessment and management of dyslipidemia in patients with endocrine diseases.

Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS).

BACKGROUND: LDL can vary considerably in its cholesterol content; thus, lowering LDL cholesterol (LDLC) as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles. This consideration is particularly applicable in diabetes mellitus, in which LDL is frequently depleted of cholesterol. METHODS: Type 2 diabetes patients randomly allocated to 10 mg/day atorvastatin (n = 1154) or to placebo (n = 1196) for 1 year were studied to compare spontaneous and statin-induced apolipoprotein B (apo B) concentrations (a measure of LDL particle concentration) at LDLC and non-HDL cholesterol (non-HDLC) concentrations proposed as statin targets in type 2 diabetes. RESULTS: Patients treated with atorvastatin produced lower serum apo B concentrations at any given LDLC concentration than patients on placebo. An LDLC concentration of 1.8 mmol/L (70 mg/dL) during atorvastatin treatment was equivalent to a non-HDLC concentration of 2.59 mmol/L (100 mg/dL) or an apo B concentration of 0.8 g/L. At the more conservative LDLC targets of 2.59 mmol/L (100 mg/dL) and 3.37 mmol/L (130 mg/dL) for non-HDLC, however, the apo B concentration exceeded the 0.9-g/L value anticipated in the recent Consensus Statement from the American Diabetes Association and the American College of Cardiology. CONCLUSIONS: The apo B concentration provides a more consistent goal for statin treatment than the LDLC or non-HDLC concentration.