Gemma Vega

Vitamin D Levels and Lipid Response to Atorvastatin

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45 ± mg/dL); whereas patients with insufficient (30–50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction.

Effect of the TNFα-308 G/A Polymorphism on the Changes Produced by Atorvastatin in Bone Mineral Density in Patients with Acute Coronary Syndrome

Aims: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome depending on the tumor necrosis factor-α (TNFα)-308 G/A polymorphism. Methods: Sixty-two patients with acute coronary syndrome (35 males and 27 females), average age 60 ± 10 years, were included. Patients were given low (10–20 mg) and high doses (40–80 mg) atorvastatin according to their baseline levels of cholesterol and triglycerides and their index of vascular risk. Patients were studied during hospital admission (baseline) and at 12 months of follow-up. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow-up. Densitometric studies were conducted in the lumbar spine (L2–L4), femoral neck and trochanter using an X-ray densitometer. The TNFα-308 G/A polymorphism was determined by the polymerase chain reaction.Results:Forty-five patients were homozygous for G/G (72.5%) and 17 were heterozygous for G/A (27.5%). The prevalence of osteoporosis (T score ≤2.5 in the lumbar spine and/or hip) was 33% for the G/G genotype and 35% for the G/A genotype, with no statistically significant differences between groups. There was a statistically significant increase in bone mineral density (BMD) in the lumbar spine (1.107 ± 0.32 vs. 1.129 ± 0.23; p = 0.0001) in patients with the G/G genotype. No changes were observed in patients with the G/A genotype. Conclusion: In patients with acute coronary syndrome, atorvastatin increases lumbar spine BMD solely in patients with the G/G genotype of the TNFα-308 G/A polymorphism.

Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin

The Wnt-LPR5 signalling pathway plays an important role in skeletal homeostasis, especially in regulating osteoblastic activity. Activation of this pathway is regulated by various inhibitors, including DKK1. The objective of this study was to evaluate DKK1 levels in patients with ischemic heart disease, the response to atorvastatin and the relationship with bone mass. Twenty-one patients with acute myocardial infarction and twenty-three controls with a mean age of 61 ± 9 years with acute coronary syndrome were included. Patients were allocated to low (10-20mg) and high doses (40-80 mg) of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk. Patients were studied at hospital admission (baseline) and at 12 months of follow up. DKK1 was determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine (L2-L4) and the femoral neck and trochanter using an X-ray densitometer. Patients had higher levels of DKK1 than controls, (111 ± 41 nmol/l versus 84 ± 27 nmol/l, p=0.014). Osteoporotic patients had higher levels of DKK1 (137.5 ± 33 nmol/l versus 95.4 ± 36 nmol/l, p=0.021). Analysis of the response to atorvastatin showed reduced DKK1 levels. In conclusion, in patients with acute coronary syndrome, atorvastatin decreases DKK1 levels. This may be a previously unreported mechanism of action of atorvastatin on bone, stimulating the Wnt signalling pathway and increasing bone mass.

Ghrelin and Bone Mass in Postmenopausal Hypertensive Women

Background: Ghrelin, a recently discovered peptide mainly secreted by the stomach, has an orexigenic effect which stimulates secretion of the growth hormone. It also has vasodilator effects which reduce blood pressure and stimulate in vitro, bone formation. Objectives: To evaluate the effect of ghrelin on bone mass and bone remodeling markers in postmenopausal hypertensive women. Material and Methods: 25 postmenopausal hypertensive women, light to moderate based on the JNC-VII criteria, were studied. They had a mean age of 58 ± 8 years, a body mass index of 28 ± 6 and a hypertension development time of 65 ± 84 months. Osteocalcin, PTHi, 25-vitamin D, ghrelin in serum and deoxypiridinoline in urine were determined in all patients. A lumbar spine densitometer was made (DXP Lunar, Madison, Wisc., USA). Results: Diminished levels of ghrelin were observed in the osteoporotic group (40 ± 19 vs. 78 ± 40, p = 0.027). When the patients were separated according to ghrelin tertiles, a greater bone mass was observed in the upper tertiles, which was associated with a decrease in the urinary deoxypiridinoline. When the total population was analyzed, no relation between the ghrelin and bone mass was found, nor with any of the parameters of calcium metabolism. Only a statistically significant relation between ghrelin and deoxypiridinoline was observed (r = –0.428, p = 0.026). Conclusions: In postmenopausal hypertensive women, ghrelin may produce a protecting effect over bone mass through an anticatabolic mechanism manifested by a decrease of bone resorption.

Role of Bone Morphogenetic Protein 2 Polymorphisms in Bone Mineral Density after the Start of Treatment with Atorvastatin

One of the pleiotropic effects of statins is their capacity to increase bone formation. This is due to, among other things, they modify BMP-2 pathway. Several experimental studies have confirmed that statins have bone anabolic properties but the consequences in bone metabolism in the clinical practice are very variable. Our hypothesis is that the clinical variability in bone metabolism response could be attributed, among other causes, to genetic factors. Therefore, we analysed polymorphisms in BMP-2 gene (rs235768, rs1980499, rs2273073 and rs1005464) in order to evaluate the role of these variants in modulating bone metabolism response to statins treatment in patients with acute coronary syndrome. Our results showed that being a carrier of the variant allele T of BMP2 rs2273073 polymorphism was associated with an increased in the total hip BMD following atorvastatin therapy. This is the first report showing an association between a polymorphism in BMP-2 gene and bone changes in response to atorvastatin treatment. This report reinforces the hypothesis that genetic factors are crucial in the clinical variability of bone metabolism changes in response to statin treatment. This article is protected by copyright. All rights reserved.