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We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (≥ 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07–4.10; p = 0.03); 2.49 (1.10–5.67; p = 0.03); 1.71 (1.10–2.67; p = 0.02); and 1.73 (1.31–2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required. [ABSTRACT FROM AUTHOR]

In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) ≤ 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and yet remains under-recognized and under-treated. Atherosclerosis is the most common cause of lower extremity PAD and pharmacological interventions that alter this central patho- genic role of atherosclerosis may alter the natural history of PAD. There is growing evidence that the renin-angiotensin system (RAS) is a signi cant mediator of this disease process and that treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with vasculopro- tective effects that are independent of the antihypertensive properties of these agents. Numerous lines of evidence suggest that ACE inhibitors directly inhibit the atherosclerotic process and improve vascular endothelial function. In patients with PAD, ACE inhibitors have been shown to improve peripheral circulation as measured by peripheral arterial blood pressure and by increases in peripheral blood flow. Preliminary evidence suggests that ACE inhibitors might improve clinical symptoms in patients with PAD. Recent evidence has confirmed that ACE inhibition is associated with a decrease in morbidity and mortality in patients with arterial disease without left ventricular dysfunction; this benefit was at least as great for the subset of patients with PAD. Overall, these data support a significant role for the RAS in the pathogenesis of all atherosclerotic diseases (including PAD) and suggest that the benefit is independent of the blood pressure lowering properties of these agents. These studies suggest that ACE inhibitor therapy should be considered in the routine management of individuals with PAD, regardless of whether they have hypertension or left ventricular dysfunction. [ABSTRACT FROM AUTHOR]