Donald Clark1, Stephen J Nicholls2, Julie St John3, Mohamed B Elshazly4, Haitham M Ahmed3, Haitham Khraishah5, Steven E Nissen3, Rishi Puri3. 1. Division of Cardiology, Department of Medicine, University of Mississippi Medical Center, Jackson. 2. Monash Cardiovascular Research Centre, Monash University, Melbourne, Australia. 3. Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio. 4. Division of Cardiology, Department of Medicine, Weill Cornell Medical College-Qatar, Education City, Doha, Qatar. 5. Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Abstract
Importance: Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events, but mechanisms and therapeutic implications underlying this association are not well understood. Objective: To examine the association of intraindividual BPV, coronary atheroma progression, and clinical outcomes using serial intravascular ultrasonography. Design, Setting, and Participants: Post hoc patient-level analysis of 7 randomized clinical trials conducted from 2004 to 2016 involving 3912 patients in multicenter, international, clinic-based primary and tertiary care centers. Adult patients with coronary artery disease who underwent serial intravascular ultrasonography in the setting of a range of medical therapies were included. Data were analyzed between November 2017 and March 2019. Exposures: Visit-to-visit BPV measured using intraindividual standard deviation over 3, 6, 12, 18, and 24 months. Main Outcomes and Measures: Percent atheroma volume (PAV) progression and major adverse cardiovascular events (defined as death, myocardial infarction, stroke, urgent revascularization for acute coronary syndrome, and hospitalization for unstable angina). Results: Of 3912 patients, the mean (SD) age was 58 (9) years, 1093 (28%) were women, and 3633 (93%) were white . Continuous change in PAV was significantly associated with systolic BPV (β, .049; 95% CI, 0.021-0.078; P = .001), diastolic BPV (β, .031; 95% CI, 0.002-0.059; P = .03), and pulse pressure variability (β, .036; 95% CI, 0.006-0.067; P = .02), without a signal for differential effect greater than or less than a mean BP of 140/90 mm Hg. The PAV progression as a binary outcome was significantly associated with systolic BPV (odds ratio, 1.09; 95% CI, 1.01-1.17; P = .02) but not diastolic BPV (odds ratio, 1.04; 95% CI, 0.97-1.11; P = .30) or pulse pressure variability (odds ratio, 1.03; 95% CI, 0.96-1.10; P = .47). Survival curves revealed a significant stepwise association between cumulative major adverse cardiovascular events and increasing quartiles of systolic BPV (Kaplan-Meier estimates for quartiles 1-4: 6.1% vs 8.5% vs 10.1% vs 12.0%, respectively; log-rank P <.001). These distinct stepwise associations were not seen with diastolic BPV or pulse pressure variability. Conclusions and Relevance: Greater BPV, particularly systolic BPV, is significantly associated with coronary atheroma progression and adverse clinical outcomes. These data suggest maintaining stable blood pressure levels may be important to further improve outcomes in patients with coronary disease.
Importance: Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events, but mechanisms and therapeutic implications underlying this association are not well understood. Objective: To examine the association of intraindividual BPV, coronary atheroma progression, and clinical outcomes using serial intravascular ultrasonography. Design, Setting, and Participants: Post hoc patient-level analysis of 7 randomized clinical trials conducted from 2004 to 2016 involving 3912 patients in multicenter, international, clinic-based primary and tertiary care centers. Adult patients with coronary artery disease who underwent serial intravascular ultrasonography in the setting of a range of medical therapies were included. Data were analyzed between November 2017 and March 2019. Exposures: Visit-to-visit BPV measured using intraindividual standard deviation over 3, 6, 12, 18, and 24 months. Main Outcomes and Measures: Percent atheroma volume (PAV) progression and major adverse cardiovascular events (defined as death, myocardial infarction, stroke, urgent revascularization for acute coronary syndrome, and hospitalization for unstable angina). Results: Of 3912 patients, the mean (SD) age was 58 (9) years, 1093 (28%) were women, and 3633 (93%) were white . Continuous change in PAV was significantly associated with systolic BPV (β, .049; 95% CI, 0.021-0.078; P = .001), diastolic BPV (β, .031; 95% CI, 0.002-0.059; P = .03), and pulse pressure variability (β, .036; 95% CI, 0.006-0.067; P = .02), without a signal for differential effect greater than or less than a mean BP of 140/90 mm Hg. The PAV progression as a binary outcome was significantly associated with systolic BPV (odds ratio, 1.09; 95% CI, 1.01-1.17; P = .02) but not diastolic BPV (odds ratio, 1.04; 95% CI, 0.97-1.11; P = .30) or pulse pressure variability (odds ratio, 1.03; 95% CI, 0.96-1.10; P = .47). Survival curves revealed a significant stepwise association between cumulative major adverse cardiovascular events and increasing quartiles of systolic BPV (Kaplan-Meier estimates for quartiles 1-4: 6.1% vs 8.5% vs 10.1% vs 12.0%, respectively; log-rank P <.001). These distinct stepwise associations were not seen with diastolic BPV or pulse pressure variability. Conclusions and Relevance: Greater BPV, particularly systolic BPV, is significantly associated with coronary atheroma progression and adverse clinical outcomes. These data suggest maintaining stable blood pressure levels may be important to further improve outcomes in patients with coronary disease.
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