Dataset Information

Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.

ABSTRACT:

Introduction and aims

Endothelial dysfunction and arterial stiffness have a prognostic value on adverse long-term outcomes in coronary artery disease (CAD) patients. We evaluated the efficacy on vascular reactivity of candesartan and analyzed predictors to control the candesartan's effect on vascular reactivity in CAD patients.

Method

Patients were prospectively enrolled and prescribed candesartan for 6 months. The effect on vascular reactivity was evaluated by the change in flow-mediated dilation (FMD) and pulse wave velocity (PWV).

Results

A total of 124 patients completed the study. The better responder in FMD change (?1.3%) showed significantly lower baseline FMD than the poor responder (P < .001). In receiver operating characteristic analysis, baseline FMD 7.5% showed optimal predictive value (sensitivity 79%, specificity 79%) for predicting better responder. The baseline endothelial dysfunction (FMD <7.5%) was the only significant predictor of the better responder to candesartan. The better responder in PWV change (?-100 cm/s) showed greater blood pressure lowering and significantly higher baseline PWV than the poor responder (both P < .05). The poor responder in both FMD and PWV showed a higher prevalence of previous myocardial infarction (38.7% vs 17.2%, P = .013).

Conclusion

The candesartan's effect on vascular reactivity is more pronounced in patients with more severe endothelial dysfunction and arterial stiffness. Poor responders on both FMD and PWV showed higher prevalence of previous myocardial infarction.

SUBMITTER: Lee SR

PROVIDER: S-EPMC5639377 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.

Lee So-Ryoung SR Chae In-Ho IH Kim Hack-Lyoung HL Kang Do-Yoon DY Kim Sang-Hyun SH Kim Hyo-Soo HS

Cardiovascular therapeutics 20171001 5

<h4>Introduction and aims</h4>Endothelial dysfunction and arterial stiffness have a prognostic value on adverse long-term outcomes in coronary artery disease (CAD) patients. We evaluated the efficacy on vascular reactivity of candesartan and analyzed predictors to control the candesartan's effect on vascular reactivity in CAD patients.<h4>Method</h4>Patients were prospectively enrolled and prescribed candesartan for 6 months. The effect on vascular reactivity was evaluated by the change in flow- ...[more]

PMID: 28796934

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Project description:ImportanceThe clinical significance of hemodynamic reactivity to mental stress in the population with coronary artery disease (CAD) is unclear.ObjectiveTo investigate the association between hemodynamic reactivity to mental stress and the risk of adverse cardiovascular events in patients with stable CAD.Design, setting, and participantsThis cohort study included individuals with stable CAD from 2 prospective studies from a university-based hospital network: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 and followed up for a median of 6.0 (IQR, 5.6-6.0) years in MIPS and 4.6 (IQR, 3.8-5.3) years in MIMS2. Data were analyzed from December 1, 2022, to February 15, 2023.ExposuresThe rate-pressure product (RPP) was calculated as the mean systolic blood pressure times the mean heart rate at rest. Rate-pressure product reactivity was calculated as the maximum RPP during a standardized mental stress test minus the RPP at rest.Main outcomes and measuresThe primary outcome was a composite of cardiovascular death or nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure.ResultsFrom the total of 938 individuals from the pooled cohort (mean [SD] age, 60.2 [10.1] years; 611 [65.1%] men), 631 participated in MIPS and 307 in MIMS2. A total of 373 individuals (39.8%) were Black, 519 (55.3%) were White, and 46 (4.9%) were of unknown race or ethnicity. The RPP increased by a mean (SD) of 77.1% (23.1%) during mental stress (mean [SD] absolute change, 5651 [2878]). For every SD decrease in RPP reactivity with mental stress, the adjusted hazard ratios for the primary and secondary end points were 1.30 (95% CI, 1.04-1.72) and 1.30 (95% CI, 1.06-1.56), respectively, in MIPS and 1.41 (95% CI, 1.06-1.97) and 1.21 (95% CI, 1.02-1.60), respectively, in MIMS2. In the pooled sample, when RPP reactivity to mental stress was added to a model including traditional clinical risk characteristics, model discrimination for adverse events improved (increase in C statistic of 5% for the primary end point; P = .009).Conclusions and relevanceIn this cohort study of individuals with stable CAD, a blunted cardiovascular reactivity to mental stress was associated with adverse outcomes. Future studies are needed to assess the clinical utility of mental stress reactivity testing in this population.

Project description:OBJECTIVE:Accumulating preclinical and epidemiologic evidence has emerged to suggest that modulation of cytochrome P450 (CYP)-mediated eicosanoid metabolism may be a viable vascular protective therapeutic strategy for the secondary prevention of coronary artery disease (CAD). The functional relationship between CYP-derived eicosanoid metabolite levels and vascular dysfunction in humans with established CAD, however, has not been evaluated. Therefore, we characterized the relationship between inter-individual variation in soluble epoxide hydrolase (sEH) and CYP ?-hydroxylase metabolism and established vascular function phenotypes predictive of prognosis in a cohort of patients with atherosclerotic cardiovascular disease. METHODS:Plasma epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHET), and 20-hydroxyeicosatetraenoic acid (20-HETE) levels were quantified by HPLC-MS/MS in 106 patients with stable, angiographically-confirmed CAD. Relationships between biomarkers of CYP-mediated eicosanoid metabolism and vascular function phenotypes were evaluated by Pearson's correlation. RESULTS:A significant inverse association was observed between 20-HETE levels (a biomarker of CYP ?-hydroxylase metabolism) and brachial artery flow-mediated dilation (r = -0.255, p = 0.010). An inverse association was also observed between 14,15-EET:DHET ratios (a biomarker of sEH metabolism) and both monocyte chemoattractant protein-1 levels (r = -0.252, p = 0.009) and a consolidated cellular adhesion molecule 'score' reflecting the levels of E-selectin and P-selectin (r = -0.216, p = 0.027). No associations with C-reactive protein or epithelial neutrophil-activating protein-78 levels were observed. CONCLUSIONS:Collectively, these findings demonstrate that enhanced CYP ?-hydroxylase and sEH metabolic function are associated with more advanced endothelial dysfunction and vascular inflammation, respectively, in patients with established atherosclerotic cardiovascular disease. These findings lay the foundation for future clinical research in this area.

Dataset Information

Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.

Introduction and aims

Method

Results

Conclusion

Publications

Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.

Similar Datasets

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