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Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors
Xianhui Qin1, Youbao Li1, Ningling Sun1
1From the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China (X.Q., Y.L., X.X., M.L., J.N., B.W., F.F.H.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S.); Centers for Metabolic Disease Research, Temple University School of Medicine, PA (H.W.); Department of Cardiology, Peking University First Hospital, Beijing, China (Y.Z., J.L., Y.H.); Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (J.W.); Department of Cardiology, Second Affiliated Hospital, Nanchang University, China (X.C.); Department of Hypertension, People's Hospital of Xinjiang Uygur Autonomous Region, the Center of Diagnosis, Treatment and Research of Hypertension in Xinjiang, Urumqi, China (N.L.); Department of Cardiovascular Medicine, the First Hospital of China Medical University, Shenyang, China (Y.S.); Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China (L.Z.); and Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.).
Insights
High homocysteine (Hcy) levels diminish the effectiveness of enalapril in lowering blood pressure for hypertensive patients. This effect was observed in both short-term and long-term treatments, impacting systolic and diastolic pressure readings.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Hypertension Research
Background:
- Hypertension is a major risk factor for cardiovascular diseases.
- Enalapril is a commonly prescribed angiotensin-converting enzyme (ACE) inhibitor for hypertension.
- Homocysteine (Hcy) is an amino acid linked to cardiovascular risk.
Purpose of the Study:
- To investigate the impact of baseline homocysteine (Hcy) concentrations on the antihypertensive response to enalapril.
- To analyze these effects in previously untreated hypertensive patients within the China Stroke Primary Prevention Trial (CSPPT).
Main Methods:
- 10,783 untreated hypertensive patients were included in the CSPPT.
- A 3-week run-in period with enalapril (10 mg daily) was followed by randomization.
- Patients received either enalapril (10 mg) plus folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years.
Main Results:
- Elevated baseline Hcy concentrations (10-15 μmol/L and ≥15 μmol/L) significantly reduced enalapril's systolic blood pressure-lowering effect.
- This reduction was evident after short-term (3 and 15 weeks) and long-term (4.5 years) enalapril treatment.
- Higher Hcy levels were associated with persistently higher systolic blood pressure throughout the study and inversely with diastolic blood pressure reduction in the short term.
Conclusions:
- Elevated homocysteine levels significantly impair the short-term and long-term antihypertensive efficacy of enalapril.
- Baseline Hcy concentration is a critical factor influencing treatment response in hypertensive individuals.
- These findings suggest Hcy levels may need consideration in tailoring antihypertensive therapy.
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.
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