calcitriol and Hyperlipidemias

Low levels of 25-hydroxyvitamin D are associated with higher risk of cardiovascular morbidity and mortality. Large trials demonstrated that statins significantly decrease cardiovascular morbidity and mortality. 7-dehydrocholesterol is the precursor of both cholesterol and vitamin D. The aim of this study was to investigate the possible effect of rosuvastatin on vitamin D metabolism.. The study was performed in a prospective cohort design. The study group consisted of 91 hyperlipidemic patients who had not been treated with lipid lowering medications. Lipid parameters, 25 hydroxyvitamin-D, 1,25-dihydroxyvitamin D, and bone alkaline phosphatase were obtained at baseline and after 8 weeks of rosuvastatin treatment.. None of the subjects withdrew from the study because of the adverse effects. The mean age was 59.9 +/- 12.5 years. The majority of the patients were male (55, 60%). Seventeen patients were diabetic, and 43 patients had systemic hypertension. There was a significant increase in 25-hydroxyvitamin D, from mean 14.0 (range 3.7- 67) to mean 36.3 (range 3.8 -117) ng/ml (p < 0.001), and also an increase of 1,25-dihydroxyvitamin D from mean 22.9 +/- 11.2 to 26.6 +/- 9.3 pg/dl (p = 0.023). Bone alkaline phosphatase decreased after 8 weeks of rosuvastatin treatment, mean 17.7 (range 2.6-214) to mean 9.5 (range 2.3-19.1) u/l (p < 0.001) rosuvastatin treatment.. This study has shown an effect of rosuvastatin on vitamin D metabolism, with an increase in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. This may be an important pleiotropic effect whereby rosuvastatin reduces mortality in patients with coronary artery disease. Further studies are needed to clarify the relationship between statins and vitamin D metabolism.

Topics: Aged; Alkaline Phosphatase; Bone and Bones; Cohort Studies; Diabetes Mellitus; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertension; Male; Middle Aged; Prospective Studies; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Vitamin D

To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies.

Topics: Absorptiometry, Photon; Animals; Aorta; Body Weight; Bone and Bones; Calcium; Calcium Oxalate; Calcium Phosphates; Cholesterol, Dietary; Diet, Atherogenic; Dietary Fats; Glycolates; Hyperlipidemias; Hyperoxaluria; Immunohistochemistry; Kidney; Kidney Calculi; Liver; Male; Microscopy, Electron; Minerals; Nephrocalcinosis; Parathyroid Hormone; Phospholipids; Proteinuria; Rats; Rats, Sprague-Dawley; Vitamin D