Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy.

Lipoprotein(a) [Lp(a)] has enhanced atherothrombotic properties. The ability of Lp(a) levels to predict adverse cardiovascular outcomes in patients undergoing coronary angiography has not been examined. The relationship between serum Lp(a) levels and both the extent of angiographic disease and 3-year incidence of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, and coronary revascularization) was investigated in 2,769 patients who underwent coronary angiography [median Lp(a) 16.4 mg/dl, elevated levels (≥30 mg/dl) in 38%]. An elevated Lp(a) was associated with a 2.3-fold [95% confidence interval (CI), 1.7-3.2, P < 0.001] greater likelihood of having a significant angiographic stenosis and 1.5-fold (95 CI, 1.3-1.7, P < 0.001) greater chance of three-vessel disease. Lp(a)≥30 mg/dl was associated with a greater rate of MACE (41.8 vs. 35.8%, P = 0.005), primarily due to a greater need for coronary revascularization (30.9 vs. 26.0%, P = 0.02). A relationship between Lp(a) levels and cardiovascular outcome was observed in patients with an LDL cholesterol (LDL-C) ≥70-100 mg/dl (P = 0.049) and >100 mg/dl (P = 0.02), but not <70 mg/dl (P = 0.77). Polymorphisms of Lp(a) were also associated with both plasma Lp(a) levels and coronary stenosis, but not a greater rate of MACE. Lp(a) levels correlate with the extent of obstructive disease and predict the need for coronary revascularization in subjects with suboptimal LDL-C control. This supports the need to intensify lipid management in patients with elevated Lp(a) levels.

Laser-induced auto-fluorescence (LIAF) as a method for assessing skin stiffness preceding diabetic ulcer formation.

Recurrent foot ulceration is a major cause of morbidity in diabetic patients. Discrepancy between the stiffness of the plantar skin and underlying soft tissues may influence the likelihood of ulceration. Tissue properties change with diabetes primarily due to high blood glucose which promotes intermolecular cross-linking of structural proteins thus leading to altered structure and function of these structural fibers. This study utilizes a non-invasive method for indirectly assessing skin tissue in the context of plantar ulcer formation in diabetic patients' feet. Control (C, n=13), and diabetic subjects with a history of ulceration (n=16) were matched based on gender, age (42-81years old) and BMI. Six subjects re-ulcerated (U) during their 1-year follow-up. At every visit, each subject's plantar skin was excited with a weak laser light (337nm) to induce tissue fluorescence at three locations on each foot. The spectral area under the curve (AUC) was calculated after background subtraction and normalization. The mean AUC was significantly higher for diabetics compared to control subjects, (mean AUC: 145.6+/-7.2, C=112.6+/-8.3, respectively, p=0.006). For those who re-ulcerated (U, n=6), skin site was not a significant factor, but AUC was diminished at the time of re-ulceration (p<0.05). The alteration of intermolecular bonds in diabetic subjects and thinning of skin prior to ulceration could account for these observations. The decrease in AUC prior to an ulcer formation suggests its potential as a marker of tissue changes, which precede ulceration in the diabetic foot.

Effect of extended-release niacin on serum lipids and on endothelial function in adults with sickle cell anemia and low high-density lipoprotein cholesterol levels.

Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD) have low apoA-I and endothelial dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with levels of HDL-C <39 mg/dl or apoA-I <99 mg/dl were randomized to 12 weeks of niacin-ER, increased in 500-mg increments to a maximum of 1,500 mg/day, or placebo. The primary outcome was the absolute change in HDL-C level after 12 weeks, with endothelial function assessed before and at the end of treatment. Niacin-ER-treated patients trended to greater increase in HDL-C level compared with placebo treatment at 12 weeks (5.1 ± 7.7 vs 0.9 ± 3.8 mg/dl, 1-tailed p = 0.07), associated with significantly greater improvements in the ratios of low-density lipoprotein to HDL-C levels (1.24 vs 1.95, p = 0.003) and apolipoprotein B to apoA-I levels (0.46 vs 0.58, p = 0.03) compared with placebo-treated patients. No improvements were detected in 3 independent vascular physiology assays of endothelial function. Thus, the relatively small changes in HDL-C levels achieved by the dose of niacin-ER used in our study are not associated with improved vascular function in patients with SCD with initially low levels of apoA-I or HDL-C.