Faculty Bibliography

Background/UNASSIGNED:Multiple studies demonstrate the benefit of a vegan diet on cardiovascular risk factors when compared to no intervention or usual dietary patterns. The aim of this study is to evaluate the effect of a vegan diet versus the American Heart Association (AHA)-recommended diet on inflammatory and glucometabolic profiles in patients with angiographically defined coronary artery disease (CAD). Study Design/UNASSIGNED:This study is a randomized, open label, blinded end-point trial of 100 patients with CAD as defined by ≥50% diameter stenosis in a coronary artery ≥2 mm in diameter on invasive angiography. Participants are randomized to 8 weeks of either a vegan or AHA-recommended diet (March 2014 and February 2017). Participants are provided weekly groceries that adhere to the guidelines of their diet. The primary endpoint is high sensitivity C-reactive concentrations. Secondary endpoints include anthropometric data, other markers of inflammation, lipid parameters, glycemic markers, endothelial function, quality of life data, and assessment of physical activity. Endpoints are measured at each visit (baseline, 4 weeks, and 8 weeks). Dietary adherence is measured by two weekly 24-hour dietary recalls, a 4-day food record during the week prior to each visit, and both plasma and urine levels of trimethylamine-N-oxide at each visit. Conclusion/UNASSIGNED:This study is the first to comprehensively assess multiple indices of inflammation and glucometabolic profile in a rigorously conducted randomized trial of patients with CAD on a vegan versus AHA-recommended diet.

Cardiovascular disease (CVD) is the leading cause of mortality in the US and is largely preventable with lifestyle and medications. Statins are among the most prescribed medications in the United States. While several large trials have shown statins to be safe and effective, rare adverse events may be seen including the development or exacerbation of ulcerative colitis (UC). A 66-year-old woman with UC (diagnosed 5 years prior; well controlled on mesalamine with rare breakthrough symptoms), hypertension, hyperlipidemia, family history of premature CAD and 15+ pack year smoking history was evaluated for primary prevention of CVD and started on atorvastatin. Upon starting atorvastatin she noted myalgias and recurrence of proctitis. A colonoscopy at that time demonstrated active inflammation in the distal 5 cm of the rectum. All symptoms abated upon discontinuing the statin. Years later she was noted to be at increased risk for CVD, with an elevated coronary calcium score of 89 and an LDL of 149, and was re-challenged with low dose rosuvastatin. Soon after initiation, the patient again experienced a flare, this time requiring steroids to achieve remission despite stopping the statin. There is a paucity of data on statin-induced colitis. One reported case of pravastatin induced severe UC lead to colectomy and subsequent death, and several cases of statin-induced colitis have been reported to manufacturers. A RCT of 64 patients with UC and mild-moderate activity given atorvastatin vs. placebo for 8 weeks showed that patients on atorvastatin had worse outcomes (an increase of partial Mayo score by 1.5 points vs. decrease by 0.31 on placebo (p = 0.04)). However, a large retrospective, matched case-control study of 9,617 cases of IBD and 46,665 controls showed any statin exposure was associated with a significantly decreased risk of IBD (OR 0.68, 95% CI 0.64-0.72): CD (0.64, 95% CI 0.59-0.71), and UC (OR 0.70, 95% CI 0.65-0.76). This effect was similar for most statins and present regardless of the intensity of therapy. Given the known benefits of statin therapy in the prevention and treatment of CVD and conflicting data about its effects on IBD, patients with UC who are eligible for statin therapy should proceed with treatment but be counseled that they may be more susceptible to a flare. If UC symptoms are exacerbated, an alternative statin should not be employed. Instead, a different class of lipid-lowering therapy should be tried

BACKGROUND: Lipoprotein(a) [Lp(a)] is an inherited atherogenic lipoprotein and an independent risk factor for atherosclerotic cardiovascular disease; however, its clinical role remains limited. OBJECTIVE: We hypothesized that Lp(a) screening in high cardiovascular risk patients could provide insight into disease pathogenesis and modify physician behavior for treatment intensification targeting traditional risk factors when Lp(a)-related risk was identified. METHODS: We screened 113 patients presenting electively for percutaneous coronary intervention (PCI) for Lp(a) who met any of the following criteria: (1) premature coronary artery disease (male age <55 years, female age <65 years); (2) family history of premature coronary artery disease; (3) progression to PCI despite well-controlled traditional risk factors (blood pressure <140/90 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL, and HbA1c <7%, and nonsmoker); or (4) progression to PCI despite at least moderate intensity statin use (simvastatin 40, atorvastatin 40-80, or rosuvastatin 20-40 mg daily). RESULTS: In this high-risk cohort, Lp(a) was elevated in nearly half of all subjects, including those with seemingly well-controlled lipids by prior guidelines, suggesting a role for Lp(a) in conferring residual cardiovascular risk. In our cohort, when screened positive, knowledge of an elevated Lp(a) did not influence referring physicians' treatment intensification targeting traditional modifiable cardiovascular risk factors (P = .18). CONCLUSION: When screened judiciously, elevated levels of Lp(a) are highly prevalent in high cardiovascular risk patients, including at a young age, presenting for PCI and may contribute to previously unappreciated residual cardiovascular risk.

BACKGROUND: The optimal blood pressure (BP) target has been a matter of debate. The recent SPRINT trial showed significant benefits of a BP target of <120 mm Hg albeit with an increase in serious adverse effects related to low BP. METHODS: PUBMED, EMBASE, and CENTRAL were searched for randomized trials comparing treating to different BP targets. Trial arms were grouped into five systolic BP target categories: 1) <160 mm Hg; 2) <150 mm Hg; 3) <140 mm Hg; 4) <130 mm Hg and 5) <120 mm Hg. Efficacy outcomes of stroke, myocardial infarction, death, cardiovascular death, heart failure and safety outcomes of serious adverse effects were evaluated using a network meta-analysis. RESULTS: Seventeen trials that enrolled 55,163 patients with 204,103 patient-years of follow-up were included. There was a significant decrease in stroke (RR=0.54; 95% CI 0.29-1.00) and myocardial infarction (RR=0.68; 95% CI 0.47-1.00) with systolic BP <120 mm Hg (vs. <160 mm Hg). Sensitivity analysis using achieved systolic BP showed a 72%, 97% and 227% increase in stroke with systolic BP of <140 mm Hg, <150 mm Hg and <160 mm respectively, when compared with systolic BP <120 mm Hg. There was no difference in death, cardiovascular death or heart failure when comparing any of the BP targets. However, the point estimate favored lower BP targets (<120 mm Hg, <130 mm Hg) when compared with higher BP targets (<140 mm Hg or <150 mm Hg). BP targets of <120 mm Hg and <130 mm Hg ranked #1 and #2 respectively, as the most efficacious target. There was a significant increase in serious adverse effects with systolic BP <120 mm Hg vs. <150 mm Hg (RR=1.83; 95% CI 1.05-3.20) or vs. <140 mm Hg (RR=2.12; 95% CI 1.46-3.08). BP targets of <140 mm Hg and <150 mm Hg ranked #1 and #2 respectively, as the safest target for the outcome of serious adverse effects. Cluster plots for combined efficacy and safety showed that a systolic BP target of <130 mm Hg had optimal balance between efficacy and safety. CONCLUSIONS: In patients with hypertension, a systolic BP target of <130 mm Hg achieved optimal balance between efficacy and safety.