Faculty Bibliography

Type 2 diabetes mellitus (T2D) is a major risk factor for cardiovascular disease (CVD), the most common cause of death in T2D. Yet, <50% of U.S. adults with T2D meet recommended guidelines for CVD prevention. The burden of T2D is increasing: by 2050, approximately 1 in 3 U.S. individuals may have T2D, and patients with T2D will comprise an increasingly large proportion of the CVD population. The authors believe it is imperative that we expand the use of therapies proven to reduce CVD risk in patients with T2D. The authors summarize evidence and guidelines for lifestyle (exercise, nutrition, and weight management) and CVD risk factor (blood pressure, cholesterol and blood lipids, glycemic control, and the use of aspirin) management for the prevention of CVD among patients with T2D. The authors believe appropriate lifestyle and CVD risk factor management has the potential to significantly reduce the burden of CVD among patients with T2D.

Patients with diabetes mellitus have increased rates of atherosclerotic cardiovascular disease (CVD) and heart failure (HF). This increase occurs despite optimal lipid-lowering therapies. We reviewed clinical trials of diabetes treatments and their effects on circulating plasma lipoproteins and CVD. Several earlier studies failed to demonstrate clear CVD benefit from diabetes therapies. In addition, triglyceride-reducing agents did not reduce overall CVD in large clinical trials although these trials were not conducted in cohorts selected as hypertriglyceridemic. Specific classes such as the thiazolidinediones increased HF. After Food and Drug Administration mandates for more rigorous safety data, recent studies have not only demonstrated CVD safety for many diabetes mellitus agents, but have also shown that certain newer medications such as empagliflozin, canagliflozin, liraglutide, and semaglutide reduce CVD. Moreover, pioglitazone use in insulin-resistant patients has resulted in decreased cerebrovascular and cardiovascular events, suggesting a protective vascular effect of this agent. Benefits from these newer classes of medications are unlikely to be because of improved lipoprotein profiles. These disparities in diabetes medication effects on CVD are likely attributable to each drug or drug class' cardiometabolic effects. Selecting medications based solely on their potential to lower hemoglobin A1C is an outdated therapeutic approach. We propose a new algorithm for treatment of patients with type II diabetes such that medication selection is based on the presence or risk of coronary artery disease and/or HF.

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.

Diabetes mellitus (diabetes) is associated with significantly increased risk of peripheral vascular disease. Diabetes is classified as a coronary heart disease (CHD) risk equivalent, but it is unknown whether diabetes is a CHD risk equivalent for peripheral vascular disease. The objective was to evaluate the odds of peripheral arterial disease (PAD) or carotid artery stenosis (CAS) among participants with diabetes, CHD, or both, compared with participants without diabetes or CHD, in a nationwide vascular screening database. We hypothesized that diabetes and CHD would confer similar odds of PAD and CAS. METHODS: A cross-sectional analysis of all eligible Life Line Screening Inc participants age 30 to 90 years with ankle brachial indices for PAD (ankle brachial index <0.9 in either leg) and carotid artery duplex ultrasonographic imaging for CAS (internal CAS >/=50%) was performed (N=3,522,890). RESULTS: Diabetes and CHD were present in 372,330 (10.7%) and 182,760 (5.8%) of participants, respectively; PAD and CAS were present in 155,000 (4.4%) and 130,347 (3.7%) of participants. After multivariable adjustment, PAD odds were 1.56 (95% CI 1.54-1.59) and 1.69 (95% CI 1.65-1.73) for participants with diabetes or CHD, respectively. Participants with both diabetes and CHD had 2.75-fold increased odds of PAD (95% CI 2.66-2.85). Findings were similar for CAS; compared with no diabetes or CHD, CAS odds increased for participants with diabetes alone (1.53, 95% CI 1.50-1.56), CHD alone (1.72, 95% CI 1.68-1.76), and both diabetes and CHD (2.57, 95% CI 2.49-2.66). Findings were consistent for women and men. CONCLUSION: In a large database of more than 3.5 million self-referred participants, diabetes was a CHD risk equivalent for PAD and CAS, and participants with comorbid diabetes and CHD had an especially robust association with PAD and CAS. Counseling regarding screening and prevention of peripheral vascular disease may be useful for patients with diabetes.

BACKGROUND: Although metabolic surgery was originally performed to treat hypercholesterolemia, the effects of contemporary bariatric surgery on serum lipids have not been systematically characterized. METHODS AND RESULTS: MEDLINE, EMBASE and Cochrane databases were searched for studies with >/=20 obese adults undergoing bariatric surgery [Roux-en-Y Gastric Bypass (RYGBP), Adjustable Gastric Banding, Bilio-Pancreatic Diversion (BPD), or Sleeve Gastrectomy]. The primary outcome was change in lipids from baseline to one-year after surgery. The search yielded 178 studies with 25,189 subjects (pre-operative BMI 45.5+/-4.8kg/m2) and 47,779 patient-years of follow-up. In patients undergoing any bariatric surgery, compared to baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low density lipoprotein cholesterol (LDL-C; -22.0mg/dL), triglycerides (-61.6mg/dL) and a significant increase in high density lipoprotein cholesterol (6.9mg/dL) at one year (P<0.00001 for all). The magnitude of this change was significantly greater than that seen in non-surgical control patients (eg LDL-C; -22.0mg/dL vs -4.3mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction<0.00001; eg LDL-C: BPD -42.5mg/dL, RYGBP -24.7mg/dL, Adjustable Gastric Banding -8.8mg/dL, Sleeve Gastrectomy -7.9mg/dL). In the cases of Adjustable Gastric Banding (TC and LDL-C) and Sleeve Gastrectomy (LDL-C), the response at one year following surgery was not significantly different from non-surgical control patients. CONCLUSIONS: Contemporary bariatric surgical techniques produce significant improvements in serum lipids, but changes vary widely, likely due to anatomic alterations unique to each procedure. These differences may be relevant in deciding the most appropriate technique for a given patient.

The global obesity epidemic and its impact on cardiovascular outcomes is a topic of ongoing debate and investigation in the cardiology community. It is well known that obesity is associated with multiple cardiovascular risk factors. Although life-style changes are the first line of therapy, they are often insufficient in achieving weight loss goals. Liraglutide, naltrexone/bupropion, and phentermine/topiramate are new agents that have been recently approved to treat obesity, but their effects on cardiovascular risk factors and outcomes are not well described. This review summarizes data currently available for these novel agents regarding drug safety, effects on major cardiovascular risk factors, impact on cardiovascular outcomes, outcomes research that is currently in progress, and areas of uncertainty. Given the impact of obesity on cardiovascular health, there is a pressing clinical need to understand the effects of these agents beyond weight loss alone.

Testosterone replacement therapy is recommended for men with clinical androgen deficiency with decades of evidence supporting its use for treatment of sexual, physical, and psychological consequences of male hypogonadism. In this updated review, the authors discuss the implications of testosterone deficiency and conflicting evidence regarding testosterone replacement therapy and its effects on the cardiovascular system. Based on mounting evidence, the authors conclude that testosterone therapy can be safely considered in men with appropriately diagnosed clinical androgen deficiency and concurrent cardiovascular risk factors and even manifest cardiovascular disease after a thorough discussion of potential risks and with guideline-recommended safety monitoring.

BACKGROUND: Diabetes mellitus (DM) and metabolic syndrome are important targets for secondary prevention in cardiovascular disease. However, the prevalence in patients undergoing elective percutaneous coronary intervention (PCI) is not well defined. We aimed to analyze the prevalence and characteristics of patients undergoing PCI with previously unrecognized prediabetes, diabetes and metabolic syndrome. METHODS: Data were collected from 740 patients undergoing elective PCI between November 2010 and March 2013 at a tertiary referral center. Prevalence of DM and prediabetes was evaluated using Hemoglobin A1c (A1c >/= 6.5% for DM, A1c 5.7-6.4% for prediabetes). A modified definition was used for metabolic syndrome [3 or more of the following criteria: body mass index (BMI) >/=30 kg/m2; triglycerides >/= 150 mg/dL; high density lipoprotein <40 mg/dL in men and <50 mg/dL in women; systolic blood pressure >/= 130 mmHg and/or diastolic >/= 85 mmHg; A1c >/= 5.7% or on therapy]. RESULTS: Mean age was 67 years, median BMI was 28.2 kg/m2 , and 39% had known DM. Of those without known DM, 8.3% and 58.5% met A1c criteria for DM and for prediabetes at time of PCI. Overall, 54.9% met criteria for metabolic syndrome (69.2% of patients with DM and 45.8% of patients without DM). CONCLUSION: Among patients undergoing elective PCI, a substantial number were identified with new DM, prediabetes, and/or metabolic syndrome. Routine screening for an abnormal glucometabolic state at the time of revascularization may be useful for identifying patients who may benefit from additional targeting of modifiable risk factors