Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients.

Abstract

OBJECTIVE:

We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial).

APPROACH AND RESULTS:

After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure-lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40-2.37) and 3.25 (95% confidence interval 1.98-4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure-lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01-1.53) and 1.70 (95% confidence interval 0.72-2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period.

CONCLUSIONS:

Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.

• Authors: Xianhui Qin, Youbao Li, Ningling Sun, Hong Wang, Yan Zhang, Jiguang Wang, Jianping Li, Xin Xu, Min Liang, Jing Nie, Binyan Wang, Xiaoshu Cheng, Nanfang Li, Yingxian Sun, Lianyou Zhao, Xiaobin Wang, Fan Fan Hou, Yong Huo
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 37 Issue 1 Pg. 166-172 (01 2017) ISSN: 1524-4636 [Electronic] United States
• PMID: 27834686 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Heart Association, Inc.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Biomarkers
• Homocysteine
• Enalapril
• Folic Acid

Topics

• Aged
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• China
• Double-Blind Method
• Enalapril (therapeutic use)
• Female
• Folic Acid (therapeutic use)
• Homocysteine (blood)
• Humans
• Hypertension (blood, drug therapy, physiopathology)
• Male
• Middle Aged
• Time Factors
• Treatment Outcome
• Up-Regulation