Factors Influencing Blood Pressure Response to Trandolapril Add-On Therapy in Patients Taking Verapamil SR (from the International Verapamil SR/Trandolapril [INVEST] Study)

Abstract

Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A→C) in the angiotensin II type 1 receptor gene (AGTR1) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by −9.1 ± 17.3 (SD) and −4.1 ± 10.1 mm Hg, respectively. The percentage of patients with BP under control (<140/90 mm Hg) increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas the decrease in systolic BP was more pronounced in younger patients, the opposite was observed for diastolic BP decrease. Diastolic BP response was also significantly associated with race. Specifically, the adjusted diastolic BP decrease was significantly smaller in Hispanics and blacks than whites (p = 0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in systolic BP and an increase in BP control similar to the other ethnic groups. There was no genetic association between AGTR1 1166A→C genotype and BP response. In conclusion, trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.We assessed factors associated with the response to add-on therapy with the angiotensinconverting enzyme (ACE) inhibitor trandolapril, including race/ethnicity, angiotensin II type 1 receptor (AGTR1 MethodsThe INVEST rationale, design, inclusion and exclusion criteria, treatment strategies, and main results were published in detail elsewhere. Briefly, after an extensive cardiovascular history and physical examination, patients were randomly assigned to either a verapamil sustained release (SR)-trandolapril-or atenolol-hydrochlorothiazide-based antihypertensive strategy. Patients were evaluated every 6 weeks for the first 6 months and then biannually for ≥2 years to assess blood pressure (BP) and adverse outcomes. The detailed BP measurement method was published previously. 1,2 The INVEST on-line data system provided detailed tracking of study medication prescriptions. 3 From 1997 to 2003, follow-up of 61,835 patient-years was accumulated, and each strategy provided excellent BP control (>70% of patients achieved BP <140/90 mm Hg) without differences in BPs between strategies. The strategies...

Determinants of Plasma Renin Activity

“…The renin-angiotensin system (RAS) plays a major role in blood pressure regulation and electrolyte metabolism 1 ; however, the overactivation of the RAS is thought to play a pivotal role in the pathophysiology of cardiovascular, 2 renal 3 and metabolic conditions. 4 Plasma renin had been associated with cardiovascular morbidity and mortality in hypertensive patients 5 , 6 and recent studies also confirmed that higher plasma renin was associated with greater cardiovascular mortality in patients referred for coronary angiography 7 and in community-based cohort studies. 8 , 9 The plasma renin activity (PRA) is affected by a number of factors, especially quantity of sodium intake.…”

Two CES1 Gene Mutations Lead to Dysfunctional Carboxylesterase 1 Activity in Man: Clinical Significance and Molecular Basis

“…Additionally, genomic DNA samples collected from various self-identified racial and ethnic groups during the course of participation in a large multicenter clinical study of combination antihypertensive treatment (INternational VErapamil SR/Trandolapril Study [INVEST]) were also available for analysis. 15 This group consisted of 355 additional white subjects, 117 black subjects, 299 subjects of Hispanic ethnicity, and 54 Asian individuals. The aberrant metabolizer, his parents, and study peers were not included in the calculation of allelic frequency because a priori information regarding their CES1 activity was known to investigators.…”

Understanding the Importance of Race/Ethnicity in the Care of the Hypertensive Patient

“…Despite less BP reduction with monotherapy with ACEIs and ARBs in Blacks [64], no causal candidate genes including ACE gene insertion/deletion (I/D) polymorphism or angiotensin type 1 receptor, AGTR1 gene, have been conclusively demonstrated [54,65,66]. Moreover, although angioedema with ACE inhibitors is more common in Blacks [67], no specific underlying genetic cause has been elucidated [62].…”