Faculty Bibliography

BACKGROUND:While progress in the prevention of cardiovascular disease (CVD) has been noted over the past several decades, there are still those who develop CVD earlier in life than others. OBJECTIVE:We investigated traditional and lifestyle CVD risk factors in young to middle-aged patients compared to older ones with obstructive coronary artery disease (CAD). METHODS:A retrospective analysis of patients with a new diagnosis of obstructive CAD undergoing coronary intervention was performed. Young to middle-aged patients were defined as those in the youngest quartile (n = 281, mean age 50 ± 6 years, 81% male) compared to the other three older quartiles combined (n = 799, mean age 69 ± 7.5 years, 71% male). Obstructive CAD was determined by angiography. RESULTS:Young to middle-aged patients compared to older ones were more likely to be male (p < 0.01), smokers (21 vs. 9%, p < 0.001), and have a higher body mass index (31 ± 6 vs. 29 ± 6 kg/m2, p < 0.001). Younger patients were less likely to eat fruits, vegetables, and fish and had fewer controlled CVD risk factors (2.7 ± 1.2 vs. 3.0 ± 1.0, p < 0.001). Compared to older patients, higher levels of psychological stress (aOR 1.6, 95% CI 1.1-2.4), financial stress (aOR 1.8, 95% CI 1.3-2.5), and low functional capacity (aOR 3.3, 95% CI 2.4-4.5) were noted in the young to middle-aged population as well. CONCLUSION/CONCLUSIONS:Lifestyle in addition to traditional CVD risk factors should be taken into account when evaluating risk for development of CVD in a younger population.

Atherosclerotic cardiovascular disease (ASCVD) is the number one cause of morbidity and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) has been implicated as one of the major risk factors causing ASCVD based on multiple hierarchical levels of evidence. The advent of powerful LDL-C lowering therapies, such as the proprotein convertase subtilisin/kexin type 9 inhibitor, have raised the question of how low to target LDL-C and whether there are any adverse safety events associated with a very low LDL-C level. The present review summarizes the available evidence and concludes that even a very low LDL-C is associated with cardiovascular benefit, although the magnitude of benefit depends on baseline ASCVD risk and the absolute change in LDL-C with pharmacologic therapy. The safety data in patients treated to very low LDL-C is reassuring, although it is inconsistent and requires longer-term follow-up.

BACKGROUND:Patients undergoing cardiovascular (CV) procedures often have suboptimal CV risk factor control and may benefit from strategies targeting healthy lifestyle behaviors and education. Implementation of prevention strategies may be particularly effective at this point of heightened motivation. METHODS:A prospective, randomized, pilot study was conducted in 400 patients undergoing a nonurgent CV procedure (cardiac catheterization ± revascularization) to evaluate the impact of different prevention strategies. Patients were randomized in a 1:1:1 fashion to usual care (UC; group A, n = 134), in-hospital CV prevention consult (PC; group B, n = 130), or PC plus behavioral intervention program (telephone-based motivational interviewing and optional tailored text messages) (group C, n = 133). The primary end point was the Δ change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to 6 month. RESULTS:The mean age was 64.6 ± 10.8 years, 23.7% were female, and 31.5% were nonwhite. After 6 months, the absolute difference in non-HDL-C for all participants was -19.8 mg/dL (95% CI -24.1 to -15.6, P < .001). There were no between-group differences in the primary end point for the combined PC groups (B and C) versus UC, with a Δ adjusted between group difference of -5.5 mg/dL (95% CI -13.1 to 2.1, P = .16). Patients in the PC groups were more likely to be on high-intensity statins at 6 months (52.9% vs 38.1%, P = .01). After excluding participants with baseline non-HDL-C <100 mg/dL (initial exclusion criterion), Δ non-HDL-C and Δ low-density lipoprotein cholesterol were improved in the PC groups compared to UC (non-HDL-C -8.13 mg/dL [-16.00 to -0.27], P = .04; low-density lipoprotein cholesterol -7.87mg/dL [-15.10 to -0.64], P = .03). CONCLUSIONS:Although non-HDL-C reduction at 6 months following a nonurgent CV procedure was not significant in the overall cohort, an increased uptake in high-potency statins may translate into improved long-term health outcomes and cost reductions.

Background and Aims: Phase 3 clinical study for a microsomal triglyceride transfer protein (MTP) inhibitor, lomitapide, in the treatment of Homozygous Familial Hypercholesterolemia (HoFH) has been associated with asymptomatic transaminase elevations and liver-fat accumulation. Lomitapide prescribing information therefore carries a warning of the risk of hepatotoxicity with use, thus, lomitapide is only available through the restricted REMS Program. Method: The Lomitapide Observational Worldwide Evaluation Registry (LOWER), is an international, multicenter, observational registry, established to prospectively assess long-term safety and efficacy of lomitapide. This analysis examines 3 years of data among patients enrolled in the registry. Results: As of March 1, 2017,163 patients with mean age of 52.3 years were enrolled in LOWERin the USA, EU, Taiwan and Canada. Exposure duration was up to 47.1 months, with 72.4% of patients receiving the drug for >12 months and 38% for 2-5 years. Mean dose was 10 mg (range 5 mg QOD-40 mg QD). The median time to elevated transaminases was 7.7 months. Patients were referred for additional liver-related evaluations for 21 (67.7%) patients with ALT or AST >=3x ULN to <5x ULN and 10 (90.9%) patients with ALT or AST >5x ULN. Further, elevated transaminases >3x ULN (n = 35, 22.3%) with data following escalation resolved spontaneously or after dose reduction or drug discontinuation. There has been no case with symptomatic hepatitis. Across the 3 years of the registry, only 7 of163 (4.3%) patients had confirmed event of special interest of hepatic transaminase elevations resulting in discontinuation of lomitapide. Conclusion: The 3-year duration of LOWER afforded the opportunity to assess the effect of chronic MTP inhibition on liver safety. Our data confirm that lomitapide is associated with frequent asymptomatic increase of transaminases, however the percentages of ALT/AST increase are less than those reported in clinical trials. The reduction of lomitapide dose or temporary interruption was associated with resolution allowing the continuation of treatment. There was no significant liver injury and no Hy's law cases. (Table presented)

BACKGROUND AND AIMS: Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. METHODS: We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. RESULTS: In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or >/=50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or >/=50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90). CONCLUSIONS: In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.

PURPOSE OF REVIEW: Many guidelines exist for the use of statins in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Few have focused on disease specific states that predispose to ASCVD. This review is intended to focus on the recommendations and evidence in inflammatory diseases that predispose to an increased risk of ASCVD beyond what conventional cardiac risk scores would predict. RECENT FINDINGS: Certain autoimmune inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), and psoriasis/psoriatic arthritis have all been shown to increase the risk of ASCVD. Other diseases such as human immunodeficiency virus (HIV) and mediastinal radiation have also been correlated with increased ASCVD. In RA and HIV, the evidence suggests a benefit to added statin therapy and society guidelines favor early initiation. The evidence for statin therapy in RA is limited to observational studies with small secondary analysis. In HIV, there is a large ongoing clinical trial to assess efficacy. In those with psoriasis and psoriatic arthritis, there is limited evidence for or against statin therapy independent of a calculated cardiac risk score. Finally, in SLE and in those with exposure to mediastinal radiation, cardiac events remain high, but evidence is limited on the beneficial effects of statin therapy. There are many individuals who have an increased risk for ASCVD above what is predicted from a cardiac risk score. It would be beneficial to create risk prediction models with statin therapy recommendations that are tailored to those predisposed to accelerated atherosclerosis.