Atorvastatin-associated rhabdomyolysis in a patient with a novel variant of the SLCO1B1 gene: A case report.

We report the case of an individual with severe hypercholesterolemia who experienced rhabdomyolysis with high dose atorvastatin. Genetic testing was undertaken to evaluate for suspected familial hypercholesterolemia (FH) and for the presence of gene variants associated with susceptibility to statin associated muscle disease. Genetic testing identified the presence of a potentially damaging variant of the hepatic xenobiotic transporter pump SLCO1B1, a single nucleotide variant (SNV) (rs77271279, c.481+1G>T) that disrupts the canonical donor splice motif. Although this variant has not previously been reported as associated with rhabdomyolysis and thus requires validation in population studies, it likely played a role in this patient's susceptibility to rhabdomyolysis based on functional assessment of the effect of this variant on SLCO1B1 protein function and given the known role of this transporter in statin uptake by the liver. The presence of this gene variant reinforced our decision to treat the patient's hypercholesterolemia with non-statin alternatives (PCSK9 inhibitor and ezetimibe). Genetic testing also identified the presence of a second SLCO1B1 gene variant, c.1200C>G (p.Phe400Leu, rs59113707) and homozygosity for an intron variant of the apolipoprotein(a) (LPA) gene (c.2604.138G>A intron variant, rs9457951) associated with increased Lp(a), a risk factor for atherosclerotic cardiovascular disease. Notably, all three variants are rare in persons of European descent but more frequent in African-Americans. These findings underscore the role of disabling mutations of the SLCO1B1 gene in statin myopathy and the need to validate these and other gene variants associated with statin myopathy in a population of patients with statin-associated muscle disease.

Intake of trans fat and all-cause mortality in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: A high intake of trans fatty acids decreases HDL cholesterol and is associated with increased LDL cholesterol, inflammation, diabetes, cancer, and mortality from cardiovascular disease. The relation between trans fat intake and all-cause mortality has not been established. OBJECTIVE: The aim of this study was to determine the relation between trans fat intake and all-cause mortality. DESIGN: We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study-a prospective cohort study of white and black men and women residing in the continental United States. Energy-adjusted trans fat intake was categorized into quintiles, and Cox-regression was used to evaluate the association between trans fat intake and all-cause mortality. RESULTS: During 7 y of follow-up, there were 1572 deaths in 18,513 participants included in REGARDS. From the first to the fifth quintile of trans fat intake, the mortality rates per 1000 person-years of follow-up (95% CIs) were 12.8 (11.3, 14.5), 14.3 (12.7, 16.2), 14.6 (13.0, 16.5), 19.0 (17.1, 21.1), and 23.6 (21.5, 25.9), respectively. After adjustment for demographic factors, education, and risk factors for mortality, the HRs (95% CIs) for all-cause mortality were 1.00, 1.03 (0.86, 1.23), 0.98 (0.82, 1.17), 1.25 (1.05, 1.48), and 1.24 (1.05, 1.48), respectively (P-trend = 0.004). The population attributable risk due to trans fat intake was 7% (95% CI: 5%, 8%). CONCLUSION: Higher trans fat intake is associated with an increased risk of all-cause mortality.

Cardiometabolic risk factors among HIV patients on antiretroviral therapy.

BACKGROUND: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. METHODS: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and 'other' (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. RESULTS: From baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. CONCLUSION: Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen.