Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.

Our 7-year follow-up study gives evidence that low HDL and HDL2 cholesterol, high VLDL cholesterol, and high total and VLDL triglycerides are powerful risk indicators for CHD events in patients with NIDDM:

Abstract-The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at Ϫ174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intimamedia thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (Pϭ0.015) associated with IMT, and this relation remained (Pϭ0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (Pϭ0.036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (PϽ0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis. Key Words: stromelysin-1 Ⅲ interleukin-6 Ⅲ DNA polymorphism Ⅲ B-mode ultrasonography Ⅲ carotid atherosclerosis Ⅲ population sample

Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.

Elevated levels of acute-phase proteins and cytokines, particularly CRP and IL-6, are strong predictors of the risk of serious coronary events in patients with UAP.

A cross-sectional study on the prevalence of atherosclerotic vascular disease (ASVD) and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects was carried out from 1982 to 1984 in East Finland (Kuopio) and West Finland (Turku), two areas known to differ markedly in prevalence of ASVD in the nondiabetic population. A total of 510 diabetic and 649 nondiabetic subjects aged 45-64 yr were examined in East Finland and 549 diabetic and 724 nondiabetic subjects of the same age in West Finland. In both areas and in both sexes the prevalence of coronary heart disease (CHD), stroke, and intermittent claudication was higher in diabetic than in nondiabetic subjects. Both in diabetic and nondiabetic subjects the prevalence of ASVD was higher in East Finland than in West Finland. In men, the East-West difference in the prevalence of symptomatic CHD and claudication was greater in diabetic than in nondiabetic subjects. In both areas and in both sexes the serum lipid pattern was more atherogenic and hypertension was more frequent in diabetic than in nondiabetic subjects. In both diabetic and nondiabetic subjects, serum total-cholesterol level was somewhat higher and hypertension was more frequent in East Finland than in West Finland. The East-West difference in serum total-cholesterol was greater in diabetic than in nondiabetic subjects. In multiple logistic analyses including cardiovascular risk factors, diabetes status, and area of residence, residence in East Finland was found to be, in addition to diabetes, a strong independent factor associated with CHD, particularly in men.

This long-term study of a well-characterized group of newly diagnosed patients strengthens the view that the prognosis in middle-aged subjects is markedly impaired and that both hyperglycemia and compositional lipoprotein abnormalities are predictors of cardiovascular mortality in patients with type 2 diabetes.

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