Derosa G, Bonaventura A, Romano D, Bianchi L, Fogari E, D'Angelo A, Maffioli P
Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy; Center for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, Pavia, Italy.
J Clin Pharm Ther. 2014 Jun;39(3):277-85. doi: 10.1111/jcpt.12139. Epub 2014 Mar 17.
There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO).
Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO.
There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies.
The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.
药物遗传学和分子生物标志物备受关注。我们的目的是评估依那普利/乐卡地平联合用药对一些用于高血压患者心血管风险分层的新兴生物标志物的影响,如脂蛋白(a) [Lp(a)]、可溶性晚期糖基化终末产物(sRAGE)、可溶性CD40配体(sCD40L)和血清髓过氧化物酶(MPO)。
345例患者参与了这项随机、双盲临床试验:120例高血压患者随机接受20 mg依那普利治疗,110例接受10 mg乐卡地平治疗,115例接受20/10 mg依那普利/乐卡地平固定复方治疗。我们在基线以及6、12、18和24个月后测量了以下指标:血压、空腹血糖(FPG)、血脂谱、Lp(a)、sRAGE、sCD40L和MPO。
与基线相比,所有组的血压均有所下降,正如预期的那样,依那普利/乐卡地平联合用药在降低血压方面比单药治疗更有效。所有组的血脂谱或FPG均未出现变化。与基线相比,乐卡地平可改善Lp(a)水平,但依那普利无此作用。依那普利/乐卡地平联合用药比单药治疗对Lp(a)水平的改善更明显。所有治疗均使sRAGE水平升高,sCD40L和MPO水平降低,依那普利/乐卡地平联合用药比单药治疗的效果更好。
依那普利/乐卡地平联合用药似乎不仅在降低血压方面优于单药治疗,而且在降低一些新兴生物标志物水平方面也更具优势,这些生物标志物可能对高血压患者的心血管风险分层有用。