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Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia.
van Wissen, S, Smilde, TJ, Trip, MD, de Boo, T, Kastelein, JJ, Stalenhoef, AF
Heart (British Cardiac Society). 2003;(8):893-6
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Abstract
BACKGROUND Raised plasma lipoprotein(a) (Lp(a)) is associated with increased risk of cardiovascular disease. It is unknown whether increased Lp(a) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia (FH) or whether statin treatment can reduce Lp(a) concentrations in the long term. OBJECTIVE To investigate Lp(a) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients. DESIGN A two year, randomised, double blind trial (the ASAP trial). PATIENTS 325 heterozygous FH patients. INTERVENTION Treatment with 80 mg atorvastatin or 40 mg simvastatin. MAIN OUTCOME MEASURE Change in Lp(a) concentrations and intima-media thickness of carotid artery segments at one year and two years. RESULTS At baseline, median Lp(a) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms, respectively (p = 0.03). In the atorvastatin arm, Lp(a) concentrations decreased to 243 mg/l after one year (p < 0.001) and to 263 mg/l after two years (p < 0.001). In the simvastatin arm, Lp(a) concentrations decreased to 437 mg/l after one year (p < 0.001) and to 417 mg/l after two years (p < 0.001). The difference in Lp(a) reduction between the two treatment arms was significant after one year (p = 0.004), but not after two years (p = 0.086). Lp(a) concentrations at baseline were not related to cardiovascular events at baseline. There was no correlation between baseline Lp(a) concentrations and low density lipoprotein cholesterol concentrations or intima-media thickness at baseline. Change in Lp(a) concentrations was not correlated with change in intima-media thickness after one or two years. CONCLUSIONS Long term statin treatment significantly lowers Lp(a) in FH patients. However, this reduction was unrelated to changes in intima-media thickness and casts doubt on the importance of Lp(a) in the progression of atherosclerotic disease in these patients.
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The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients.
Chertow, GM, Raggi, P, McCarthy, JT, Schulman, G, Silberzweig, J, Kuhlik, A, Goodman, WG, Boulay, A, Burke, SK, Toto, RD
American journal of nephrology. 2003;(5):307-14
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Abstract
BACKGROUND We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.