Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.

Complex stenosis morphology predicts late reocclusion during follow-up after myocardial infarction in patients with patent infarct-related coronary arteries.

BACKGROUND: Whether angiographic morphology of infarct-related residual stenoses continues to affect prognosis after discharge is not known. METHODS: We studied 175 patients after their myocardial infarction who required nonurgent coronary angioplasty for residual myocardial ischemia. The findings at diagnostic coronary angiography were compared with those before angioplasty (mean of 7 months later). Infarct-related stenoses were classified as complex or smooth. Stenosis progression was defined as >0.5 mm diameter reduction. RESULTS: One hundred twenty-one (69%) infarct-related stenoses were complex. At restudy, total occlusion was found in 41 (35%) of the infarct-related complex stenoses compared with 7 (13%) smooth stenoses (P = .001). Reocclusion occurred in 16 (55%) of 29 complex infarct-related stenoses with thrombus, compared with 25 (28%) of 88 without thrombus (P = .01). During follow-up, 46 patients (26%) had cardiac events. Of these, 70% had complex lesions at study entry compared with 30% smooth (P < .05). CONCLUSIONS: Residual angiographically complex stenoses after an uncomplicated myocardial infarction are associated with a greater risk of reocclusion and may predispose to coronary events at follow-up.

Serum sialic acid concentration is not associated with the extent or severity of coronary artery disease in patients with stable angina pectoris.

BACKGROUND: Total serum sialic acid concentration has been reported to predict death from cardiovascular disease. This study was performed to assess the relation between serum sialic acid concentration and the angiographic extent and severity of coronary atheroma in patients with stable angina. METHODS: Quantitative coronary angiography was performed in 40 patients with stable angina with either triple-vessel disease (23 patients) or normal/nearly normal coronary arteries (17 patients). A colorimetric assay for the enzymatic determination of serum sialic acid was used. RESULTS: Serum sialic acid concentration was not significantly different in patients with normal or nearly normal coronary angiograms compared with those with triple-vessel disease (68+/-10 mg/100 mL and 68+/-11 mg/100 mL, respectively). Neither was there any association between the extent or severity of coronary disease and serum sialic acid levels. CONCLUSIONS: Serum sialic acid concentration does not appear to be associated with the extent or severity of coronary artery disease in patients with stable angina pectoris. Thus the previously described association between serum sialic acid and cardiovascular death may reflect the role of mechanisms other than the severity of coronary artery narrowings.

Differential plasma endothelin levels in subgroups of patients with angina and angiographically normal coronary arteries. Coronary Artery Disease Research Group.

BACKGROUND: Raised plasma endothelin concentrations have previously been reported in patients with cardiac syndrome X, but it is not known whether these levels vary between clinically distinct subgroups in this heterogeneous condition. METHODS AND RESULTS: We compared plasma immunoreactive endothelin levels in 54 patients with angina pectoris and normal coronary angiograms and 21 healthy control subjects. The patient group was divided into 4 clinically distinct subgroups: 7 with left bundle branch block (group A); 7 with previous myocardial infarction (group B); 24 with positive exercise electrocardiography (group C); and 16 with negative exercise electrocardiography (group D). The plasma endothelin concentration was significantly higher in patients compared with control subjects (3.7 [2.9 to 4.3] vs 2.96 [2.4 to 3.4] pg/mL, respectively, median [interquartile range]; P=0.002). Endothelin concentrations were most significantly elevated in group A and group B (4.5 [3.6 to 5.2] pg/mL; P=0.005 and 4.1 [3.9 to 4.5] pg/mL; P=0.001, respectively). Plasma endothelin concentrations were also significantly elevated in group C (3.7 [2.8 to 4.1] pg/mL; P=0.02) but not in group D (3.0 [2.5 to 3.8] pg/mL; P=0.3). CONCLUSIONS: Plasma endothelin concentration is elevated in patients with angina pectoris and angiographically normal coronary arteries, particularly those with left bundle branch block or previous myocardial infarction.

Increased ventricular sialylation in patients with heart failure secondary to ischemic heart disease.

BACKGROUND: Elevated serum sialic acids are associated with increased cardiovascular mortality, but sialic acid levels have not been studied in cardiac tissue. METHODS: Myocardial samples were obtained at the time of transplantation from 23 patients (age 54 +/- 12 years) with heart failure secondary to ischemic heart disease and 16 patients (age 51 +/- 7 years) with idiopathic dilated cardiomyopathy (DCM). A control group comprised postmortem samples obtained from 14 patients (age 70 +/- 5 years) who died of non-cardiovascular causes. Ventricular sialylation was quantitated using the sialic acid-specific lectins Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) using a chemiluminescence assay. Results are expressed as the percentage (+/-standard error of the mean) of the binding of lectin to a standardized control sample of human myocardium. RESULTS: Ventricular sialylation recognized by MAA was 55 +/- 7% in patients with heart failure secondary to ischemic heart disease compared with 26 +/- 7% for DCM (p = 0.006) and 32 +/- 8% for controls (p = 0.04), and that recognized by SNA was 69 +/- 7% in patients with heart failure secondary to ischemic heart disease compared with 42 +/- 6% for DCM (p = 0.006) and 38 +/- 7% for controls (p = 0.006). No significant difference in ventricular sialylation was observed between patients with DCM and controls. CONCLUSION: Myocardial levels of sialic acids are significantly increased in patients with heart failure secondary to ischemic heart disease compared with patients with idiopathic dilated cardiomyopathy and controls. Our findings are important in view of recent reports of an association between serum sialic acid concentration and cardiovascular mortality and require further investigation.

The bacterial flora of the forehead and back of Alaskan native villagers in summer and in winter.

The bacterial flora of the forehead and back of Eskimo and Indian villagers in arctic Alaska was determined in midsummer and in winter (temperature -29 degrees to -46 degrees C). Specimens collected by the wet swab method were transported overnight, chilled, to Seattle in buffered diluent with Triton X-100. Control tests showed good survival of principal skin organisms with moderate or large initial populations and a disproportionately greater loss with an initial sparse population. Results of these studies are compared with earlier studies of the forehead flora of a Seattle urban population. On most Alaskan subjects Propionibacterium acnes was more abundant than staphylococci on both sites and both organisms had greater population densities on the forehead than on the back. Population densities for P. acnes varied from none detected to more than 10(6) per cm2 on the forehead and 10(5) per cm2 on the back. For coagulase-negative staphylococci the range was from none detected to more than 10(5) per cm2 on the forehead and the back. The proportion of subjects with relatively abundant or relatively sparse populations of P. acnes and of staphylococci did not change seasonally. Of 51 staphylococcal isolates, 65% were S. epidermidis, 22% S. capitis, and 10% S. hominis. P. saccharolyticus was found on a minority of subjects on both sites. The kinds of organisms found on the forehead and their variable individual population densities were essentially the same on the Alaskan villagers and the Seattle subjects.