Reduction in hsCRP levels is associated with decreased incidence of cardiovascular events in Japanese hypertensive women but not in men

Abstract

To test our hypothesis that the magnitude of reduction in hsCRP achieved by antihypertensive medications may predict the benefit for cardiovascular outcomes in hypertensive individuals, we performed subanalysis of the ATTEMPT-CVD study. The hypertensive participants enrolled in the ATTMEPT-CVD study were categorized into two groups according to whether achieved reduction in hsCRP levels at 6 months after initiation of antihypertensive medications from baseline was equal to or greater than 40% (responder group) or less than 40% (non-responder group). Baseline characteristics and blood pressure during follow-up period were similar between the groups. For women, the incidence of cardiovascular events was significantly less in responder group than non-responder group (P < 0.0221). However, for men, there was no significant difference between the groups regarding incident cardiovascular events (P = 0.2434). There was a significant interaction (P = 0.0187) between sexes for incident cardiovascular events. Our results provide the evidence suggesting that substantial reduction (40% or greater reduction) in hsCRP on antihypertensive medication predicts the benefit for cardiovascular outcomes in hypertensive women but it does not in hypertensive men. The magnitude of achieved reduction in hsCRP by antihypertensive medications seems to be a useful indicator of successful treatment in Japanese hypertensive women.This trial was registered with ClinicalTrials.gov, number NCT01075698.

Conflict of interest statement

Shokei Kim-Mitsuyama has received consultancy fees/honoraria/research grant from Astellas, Daiichi-Sankyo, and Takeda. Osamu Yasuda has received consultancy fees/honoraria/research grant from Otsuka Pharmaceutical Co., Ltd and Sanwa Kagaku Kenkyusho Co., Ltd. Koichi Node has received consultancy fees/honoraria/research grant from Boerhinger Ingelheim. Hideaki Jinnouchi has received consultancy fees/honoraria/research grant from AstraZeneca Pharmaceuticals, Astellas Pharma, Boehringer Ingelheim, Daiichi-sankyo, Eli Lilly, Takeda, Novartis Pharmaceuticals, Novo Nordisk and Sanofi. Kunihiko Matsui has received consultancy fees/honoraria/research grant from Daiici-Sankyo, Japan Boehringer-Ingelheim. The other authors declare no competing interests.

Figures

Figure 1

Serum hsCRP concentrations at baseline and at 6, 12, 24 and 36 months after initiation of antihypertensive medications in responder group and non-responder group for male (A) and female (B). Box plots indicate 25th percentile, median, and 75th percentile and whiskers indicate the minimum and maximum. Responder the group with 40% or greater reduction in hsCRP at 6 months from baseline; Non-responder the group with less than 40% reduction in hsCRP at 6 months from baseline; NS not significant.

Figure 2

Kaplan–Meier curves for composite cardiovascular and renal events in responder group and non-responder group for overall patients (A), male (B) and female (C). In overall patients (A), there was 22 and 64 events in responder group (n = 315) and non-responder group (n = 847). In male (B), there was 20 and 38 events in responder group (n = 192) and non-responder group (n = 480), respectively. In female (C), there were 2 and 26 events in responder group (n = 123) and non-responder group (n = 367), respectively. Abbreviations used are the same as in Fig. 1.

Figure 3

Time course of blood pressure (BP) during follow-up period in responder group and non-responder group for male (A) and female (B). Numerical values at each time point indicate the mean BP for both groups. Abbreviations used are the same as in Fig. 1.

Figure 4

Kaplan–Meier curves for composite cardiovascular and renal events stratified by quartiles of baseline hsCRP levels for overall patients (A), male (B) and female (C). In overall patients (A), the number of occurrence of events was 21, 20, 12, and 33 in Q1 (n = 292), Q2 (n = 290), Q3 (n = 290), and Q4 (n = 290), respectively. In male (B), the number of occurrence of events was 12, 13, 7, and 26 in Q1 (n = 168), Q2 (n = 168), Q3 (n = 167), and Q4 (n = 169), respectively. In female (C), the number of occurrence of events was 9, 7, 3, and 9 in Q1 (n = 122), Q2 (n = 123), Q3 (n = 121), and Q4 (n = 124), respectively.