Faculty Bibliography

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).

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.

Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe. Although guidelines advocate aggressive management of lipid parameters in diabetes, most guidelines do not address treatment of dyslipidemia in prediabetes despite the increased atherosclerotic cardiovascular disease (ASCVD) risk. Several criteria are used to diagnose prediabetes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and HbA1c of 5.7-6.4%. Individuals with prediabetes have a greater risk of diabetes, a higher prevalence of dyslipidemia with a more atherogenic lipid profile and an increased risk of ASCVD. In addition to calculating ASCVD risk using traditional methods, an OGTT may further stratify risk. Those with 1-hour plasma glucose ≥8.6 mmol/L (155 mg/dL) and/or 2-hour ≥7.8 mmol/L (140 mg/dL) (IGT) have a greater risk of ASCVD. Diet and lifestyle modification are fundamental in prediabetes. Statins, ezetimibe and PCSK9 inhibitors are recommended in people requiring pharmacotherapy. Although high-intensity statins may increase risk of diabetes, this is acceptable because of the greater reduction of ASCVD. The LDL-C goal in prediabetes should be individualized. In those with IGT and/or elevated 1-hour plasma glucose, the same intensive approach to dyslipidemia as recommended for diabetes should be considered, particularly if other ASCVD risk factors are present.

PURPOSE/OBJECTIVE: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/RESULTS: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/CONCLUSIONS: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.

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.

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.

INTRODUCTION/BACKGROUND:Physician burnout, wellness, and resilience have become increasingly important topics of discussion worldwide. While studies have assessed burnout globally in various individual countries, few studies directly compare or analyze gender-based physician burnout among different global regions. METHODS:Female physicians attending the Medical Women's International Association (MWIA) Centennial Congress completed the Copenhagen Burnout Inventory (CBI) which evaluates personal-, work-, and patient-related burnout using a scale of 0 to 100. Results were analyzed using descriptive statistics and 1-way ANOVA to compare burnout scores amongst women physicians from different global regions. RESULTS:Of 100 physicians invited to participate, 76 provided responses and 71 met the inclusion criteria. Mean burnout scores were highest amongst women from Africa in all categories. Mean work-related, patient-related, and personal-related burnout scores were significantly lower for physicians in Europe compared to Africa (p = 0.05) when evaluated using a 1-way ANOVA, with no statistically significant differences between other regions. DISCUSSION/CONCLUSIONS:The data suggests that there may be regional differences in the prevalence of burnout in women physicians. Various factors could play a role in explaining the higher burnout scores in female physicians in Africa, including younger average age, establishing practice during childbearing years, and significant physician shortage. Through this study, we have begun to explore the cultural and geographical context related to women's mental and physical wellbeing in the medical field. Further research should focus on the gender-specific contributors to burnout among different global regions, so that methods can be implemented on a systemic level to alleviate burnout.