Faculty Bibliography

Testosterone therapy is recommended for men with symptomatic androgen deficiency and unequivocally low testosterone levels. Although the prevalence of hypogonadism seems relatively constant, studies of prescribing patterns in both the United States and the United Kingdom show a dramatic increase in testosterone prescription in recent years, possibly due to increased marketing and inappropriate therapy. Concurrent with this, there has been growing concern regarding the potential adverse effects of testosterone therapy, particularly its cardiovascular risks. In this review, we present our current understanding of the implications of testosterone deficiency, as well as the conflicting evidence surrounding the cardiovascular effects of testosterone replacement therapy. Although there is a lack of adequate data, based on the current evidence, we conclude that testosterone therapy can be safely considered in men with appropriately diagnosed clinical androgen deficiency and increased cardiovascular risk after a thorough discussion of potential risks and with guideline recommended safety monitoring.

BACKGROUND: The American Heart Association recommends targeting 7 cardiovascular (CV) health metrics to reduce morbidity and mortality. Control of these targets in patients undergoing CV intervention is uncertain. METHODS: We prospectively studied patients undergoing elective percutaneous coronary or peripheral intervention from November 2010 to May 2012. We recorded data on patient demographics, clinical characteristics, and social history. Risk factor control was categorized as ideal, intermediate, or poor according to the 7 American Heart Association-defined CV health metrics (smoking status, body mass index, physical activity, diet, cholesterol, blood pressure, and metabolic control). Linear regression model was used to evaluate the association between baseline characteristics and poor CV health. RESULTS: Among 830 consecutive patients enrolled, mean age is 67.3 +/- 10.8 years, 74.2% are male, and 62.1% are white. The adequacy of achievement of ideal CV health is suboptimal in our cohort; the mean number of ideal CV metrics is 2.15 +/- 1.06. Less than 1 in 10 (9.7%) met >/=4 ideal CV health metrics. After multivariate analysis, male sex (P = .04), nonwhite race (P = .01), prior coronary artery disease (P < .01), prior peripheral arterial disease (P < .01), and history of depression (P = .01) were significantly associated with poor CV health. CONCLUSIONS: Among patients referred for elective CV intervention, achievement of ideal CV health is poor. Elective interventions represent an opportunity to identify and target CV health for risk factor control and secondary prevention.

Statins are the first line pharmacotherapy for cholesterol reduction. Use of these drugs in large, randomized clinical trials have consistently shown significant reductions in major vascular events including death, myocardial infarction, stroke, and coronary revascularization. The updated guidelines for the treatment of high blood cholesterol from the ACC/AHA, will lead to a rise in the number of patients taking statins. Hence, statin intolerance may subsequently increase, emphasizing the need to understand and treat this important problem.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 11 April 2014; doi:10.1038/clpt.2014.84.

OBJECTIVEThe aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease (lower extremity peripheral artery disease [PAD], carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]).RESEARCH DESIGN AND METHODSPrevalence of vascular disease was evaluated in 3,696,778 participants of the Life Line Screening survey between 2003 and 2008. PAD was defined as ankle-brachial pressure index <0.90 or prior revascularization, CAS as >/=50% stenosis or prior revascularization, and AAA as infrarenal aortic diameter >/=3 cm or prior repair. Odds ratios (ORs) and 95% CIs were assessed using logistic regression modeling.RESULTSDiabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA were significantly higher (P < 0.0001) in participants with compared with those without diabetes. After multivariate adjustment for baseline demographics and clinical risk factors, a significant interaction existed between diabetes and vascular disease phenotype (P < 0.0001). Diabetes was associated with increased odds of PAD (OR 1.42 [95% CI 1.41-1.4]; P < 0.0001) and CAS (1.45 [1.43-1.47]; P < 0.0001) but decreased odds of AAA (0.86 [0.84-0.88]; P < 0.0001). The strength of association increased with increasing severity of disease in each vascular phenotype, and this association persisted in the population with asymptomatic vascular disease.CONCLUSIONSIn a large population-based study, the association between diabetes and vascular disease differed according to vascular phenotype. Future studies exploring the mechanism for these vascular-specific differences are needed.

Periprocedural hyperglycemia is an independent predictor of mortality in patients who underwent percutaneous coronary intervention (PCI). However, periprocedural management of blood glucose is not standardized. The effects of routinely continuing long-acting glucose-lowering medications before coronary angiography with possible PCI on periprocedural glycemic control have not been investigated. Patients with diabetes mellitus (DM; n = 172) were randomized to continue (Continue group; n = 86) or hold (Hold group; n = 86) their clinically prescribed long-acting glucose-lowering medications before the procedure. The primary end point was glucose level on procedural access. In a subset of patients (no DM group: n = 25; Continue group: n = 25; and Hold group: n = 25), selected measures of platelet activity that change acutely were assessed. Patients with DM randomized to the Continue group had lower blood glucose levels on procedural access compared with those randomized to the Hold group (117 [97 to 151] vs 134 [117 to 172] mg/dl, p = 0.002). There were two hypoglycemic events in the Continue group and none in the Hold group, and no adverse events in either group. Selected markers of platelet activity differed across the no DM, Continue, and Hold groups (leukocyte platelet aggregates: 8.1% [7.2 to 10.4], 8.7% [6.9 to 11.4], 10.9% [8.6 to 14.7], p = 0.007; monocyte platelet aggregates: 14.0% [10.3 to 16.3], 20.8% [16.2 to 27.0], 22.5% [15.2 to 35.4], p <0.001; soluble p-selectin: 51.9 ng/ml [39.7 to 74.0], 59.1 ng/ml [46.8 to 73.2], 72.2 ng/ml [58.4 to 77.4], p = 0.014). In conclusion, routinely continuing clinically prescribed long-acting glucose-lowering medications before coronary angiography with possible PCI help achieve periprocedural euglycemia, appear safe, and should be considered as a strategy for achieving periprocedural glycemic control.

OPINION STATEMENT: With the advent of noninvasive 24-hour ambulatory blood pressure monitoring (ABPM), clinicians have access to a wealth of individualized data for the hypertensive patient. This has led to a greater understanding of the pathophysiology of hypertension and its complications. This tool has provided more precise diagnostic criteria for hypertension and helped discover those with white coat and masked hypertension. Patterns noted on ABPM and correlated with outcomes have allowed for more accurate identification of patients at high risk of cardiovascular (CV) events, and have offered an additional prognostic tool. In addition, ABPM allows for the assessment of the efficacy and adequacy of blood pressure treatment. In the current paper, we will describe the essential components of ABPM, review the evidence detailing the prognostic information that can be derived from its use, highlight clinical scenarios wherein ABPM can offer invaluable diagnostic information, and describe applications of ABPM that evaluate the efficacy of treatment of the hypertensive patient.

Despite a better understanding of cardiovascular risk factors and attempts at optimal management, diabetes-related macrovascular events remain a significant cause of morbidity and mortality in the United States and worldwide. The trials to date have validated strict glycemic control as a method to achieve sustained reductions in the rate of nephropathy, neuropathy, and retinopathy due to diabetes. For these microvascular complications, the closer hemoglobin A1c is to normal levels, the better the outcome. Although reducing hemoglobin A1c levels to 7% has been shown to reduce macrovascular events, demonstrating an additional reduction in macrovascular events with tighter glycemic control has been more difficult to achieve. A careful review of recent trials, however, has demonstrated that treatment early in the disease course and the ability to safely maintain lower hemoglobin A1c levels might be critical factors in further reducing macrovascular events. In conclusion, with the introduction of novel antidiabetic agents, future trials using these drugs might be able to definitively establish the safety and efficacy of reducing cardiovascular events with stringent glycemic control; however, the current evidence is inconsistent.