Dimitrow Pawel Petkow, Jawień Marek, Gackowski Andrzej
Institute of Cardiology CMUJ, Cracow, Poland.
J Heart Valve Dis. 2011 Jan;20(1):18-22.
Following the SEAS and SALTIRE studies in moderate-to-severe aortic stenosis (AS), it was postulated that the statin treatment had been initiated far too late during the disease course. Thus, the study aim was to assess the effect of four-week atorvastatin treatment (20 mg/day) on levels of calcification biomarkers in patients with early-stage disease (i.e., aortic sclerosis or mild AS).
In total, 33 patients (18 males, 15 females; mean age 70 +/- 8 years) with aortic sclerosis or mild AS, who had never received statin treatment, were enrolled into the study. According to their baseline lipid levels, 17 patients were hypercholesterolemic and 16 normocholesterolemic. Hence, rather than apply randomization, all patients were administered atorvastatin at a moderate dose level. Plasma levels of three biomarkers of calcification were measured, namely osteoprotegerin (OPG), osteopontin (OPN), and soluble receptor activator of nuclear factor (NF)-kappaB ligand (sRANKL).
Plasma levels of all three biomarkers were decreased after atorvastatin treatment. OPG levels fell from 13.23 +/- 5.33 to 10.92 +/- 5.34 pmol/l (p < 0.05), sRANKL from 105.36 +/- 69.47 to 86.74 +/- 71.36 ng/ml (p < 0.05), and OPN from 31.60 +/- 20.29 to 28.45 +/- 15.98 ng/ml (p = NS). When comparing patients with no/mild valvular calcification to those with moderate valvular calcification, only the OPG level before atorvastatin was statistically higher in patients from the latter group: 11.44 +/- 4.51 versus 16.09 +/- 5.67 pmol/l (p < 0.05).
Atorvastatin, at a dose level of 20 mg per day, reduced the plasma levels of calcification biomarkers in patients with aortic sclerosis and mild AS. The pre-atorvastatin OPG level was significantly higher when the aortic valve was moderately calcified, despite a persistent low transvalvular gradient.
在中重度主动脉瓣狭窄（AS）的SEAS和SALTIRE研究之后，有人推测他汀类药物治疗在疾病进程中启动得太晚。因此，本研究的目的是评估四周阿托伐他汀治疗（20毫克/天）对疾病早期患者（即主动脉瓣硬化或轻度AS）钙化生物标志物水平的影响。
总共33例从未接受过他汀类药物治疗的主动脉瓣硬化或轻度AS患者（18例男性，15例女性；平均年龄70±8岁）纳入本研究。根据他们的基线血脂水平，17例患者为高胆固醇血症，16例为正常胆固醇血症。因此，所有患者均给予中等剂量水平的阿托伐他汀，而非采用随机分组。测量了三种钙化生物标志物的血浆水平，即骨保护素（OPG）、骨桥蛋白（OPN）和核因子（NF）-κB配体可溶性受体激活剂（sRANKL）。
阿托伐他汀治疗后，所有三种生物标志物的血浆水平均下降。OPG水平从13.23±5.33皮摩尔/升降至10.92±5.34皮摩尔/升（p<0.05），sRANKL从105.36±69.47纳克/毫升降至86.74±71.36纳克/毫升（p<0.05），OPN从31.60±20.29纳克/毫升降至28.45±15.98纳克/毫升（p=无统计学意义）。将无/轻度瓣膜钙化患者与中度瓣膜钙化患者进行比较时，阿托伐他汀治疗前，仅后一组患者的OPG水平在统计学上更高：11.44±4.51皮摩尔/升对16.09±5.67皮摩尔/升（p<0.05）。
每天20毫克剂量的阿托伐他汀可降低主动脉瓣硬化和轻度AS患者的钙化生物标志物血浆水平。尽管跨瓣膜梯度持续较低，但当主动脉瓣中度钙化时，阿托伐他汀治疗前的OPG水平显著更高。
