Within the normal range, higher serum phosphate concentrations are associated with cardiovascular events and mortality in individuals with chronic kidney disease (CKD) and in those with normal kidney function. Experimental models suggest that phosphate has a direct calcifying effect on vascular smooth muscle. We examined associations of serum phosphate concentrations with vascular and valvular calcification in 439 participants from the Multi-Ethnic Study of Atherosclerosis who had moderate CKD and no clinical cardiovascular disease. Serum phosphate concentrations were within the normal range (2.5 to 4.5 mg/dl) in 95% of study participants. The prevalence of calcification in the coronary arteries, descending thoracic aorta, aortic valve, and mitral valve was 67, 49, 25, and 20%, respectively, measured by electron-beam or multi-detector row computed tomography. After adjustment for demographics and estimated GFR, each 1-mg/dl increment in serum phosphate concentration was associated with a 21% (P ϭ 0.002), 33% (P ϭ 0.001), 25% (P ϭ 0.16), and 62% (P ϭ 0.007) greater prevalence of coronary artery, thoracic, aortic valve, and mitral valve calcification, respectively. Adjustment for traditional risk factors for atherosclerosis, parathyroid hormone, or 1,25-dihydroxyvitamin D levels did not alter these associations. In conclusion, higher serum phosphate concentrations, although still within the normal range, are associated with a greater prevalence of vascular and valvular calcification in people with moderate CKD. It remains to be determined whether lowering phosphate concentrations will impact calcification risk in the setting of kidney disease.

Results: Fifty-nine (4%) individuals had high ABI (>1.30), a marker of peripheral arterial stiffness. Participants with phosphorus levels >4 mg/dl had greater than four-fold risk for high ABI compared with participants with phosphate levels <3 mg/dl (relative risk 4.6; 95% confidence interval 1.6 to 13.2; P ‫؍‬ 0.01) after adjustment for demographics, traditional CVD risk factors, and kidney function. Higher phosphorus levels were also associated with greater pulse pressure and lesser large and small artery elasticity in unadjusted models, but these associations were attenuated after adjustment.Conclusions: Higher phosphorus levels are strongly associated with high ABI but not pulse pressure or large or small artery elasticity. If confirmed in future studies, then the association of higher phosphorus concentrations with CVD events may be partially mediated through peripheral arterial stiffness.

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We studied the incidence and progression of coronary artery calcification in people with early chronic kidney disease. We used a cohort of 562 adult patients with chronic kidney disease who had an estimated glomerular filtration rate of <60 ml/min/1.73 m2, in a community-based study of people without clinical cardiovascular disease, the Multi-Ethnic Study of Atherosclerosis. The majority had stage 3 disease. Coronary artery calcification was measured at baseline and again approximately 1.6 or 3.2 years later. The prevalence of coronary artery calcification at baseline was 66%, and its adjusted prevalence was 24% lower in African Americans as compared to Caucasians. The incidence of coronary artery calcification was 6.1% per year in women and 14.8% in men. Coronary artery calcification progressed in approximately 17% of subjects per year across all subgroups, and diabetes was associated with a 65% greater adjusted risk of progression. Male gender and diabetes were the only factors associated with adjusted coronary artery calcification incidence and progression, respectively. Our study shows that coronary artery calcification is common in people with stage 3 disease, progresses rapidly, and may contribute to cardiovascular risk.

Vascular abnormalities may exist before clinical hypertension. Using Poisson regression, the authors studied the association of coronary artery calcium (CAC), common carotid intima-media thickness (CIMT), aortic distensibility, and large and small arterial elasticity with incident hypertension among 2,512 normotensive US adults free of cardiovascular disease. Incidence rate ratios for incident hypertension (blood pressure > or =140/90 mm Hg or new antihypertensive medication) were calculated. Increased CAC was associated with incident hypertension in demographics-adjusted models (incidence rate ratio (IRR) = 1.35, 95% confidence interval (CI): 1.04, 1.75; IRR = 1.35, 95% CI: 1.02, 1.78; and IRR = 1.59, 95% CI: 1.12, 2.25 for CAC scores of 30-99, 100-399, and > or =400, respectively) but was attenuated after further adjustment. Increased common CIMT was associated with incident hypertension (IRR = 1.77, 95% CI: 1.28, 2.46 for quintile 4; IRR = 1.80, 95% CI: 1.28, 2.53 for quintile 5). Participants with the lowest, compared with the highest, aortic distensibility had an increased risk of hypertension (IRR = 1.75, 95% CI: 1.10, 2.79), as did those with the lowest large arterial elasticity (IRR = 1.49, 95% CI: 1.11, 1.99). Lower small arterial elasticity was incrementally associated with incident hypertension starting at quintile 2 (IRR = 2.01, 95% CI: 1.39, 2.91; IRR = 2.47, 95% CI: 1.71, 3.57; IRR = 2.73, 95% CI: 1.88, 3.95; and IRR = 2.85, 95% CI: 1.95, 4.16). Structural and functional vascular abnormalities are independent predictors of incident hypertension. These findings are important for understanding the pathogenesis of hypertension.

Available evidence suggests that migraines and preeclampsia may reflect an underlying predisposition toward ischemic injury. More rigorous epidemiologic research is warranted, after consideration of several important methodologic issues.

Our findings are consistent with reports from six of eight previous studies on the topic. Nevertheless, prospective cohort studies are needed to further evaluate the extent to which migraines and/or its treatments are associated with preeclampsia risk.

Moderate pre-pregnancy caffeinated coffee consumption may have a protective association with GDM. Prospective studies, including a wider range of consumption habits, are necessary.