Comparison of pulse wave velocity and hypertensive response to exercise in predicting incidence of resistant hypertension

Abstract

Abstract Background Resistant hypertension (RH) is strongly associated with occurrence of major cardiovascular events and death. Hypertensive response to exercise (HRE) and arterial stiffness estimated by peripheral pulse wave velocity (PWV) are surrogate markers of incident hypertension, whereas their role in predicting RH development remains uncertain. Purpose Explore the predictive role of PWV and HRE in incident RH. Methods A Comparison of HRE and PWV in predicting development of RH was performed in retrospective study with a cohort of 198 patients with known coronary artery disease (CAD). The patients performed two Bruce protocol stress tests (STs) between 01/2009 and 12/2022. The first ST was used to assess HRE and estimated PWV (ePWV) in predicting occurrence of apparent treatment-resistant hypertension (aTRH). ePWV was calculated using age and blood pressure, as previously described (1). HRE response was defined either as systolic BP (SBP) > 210 mmHg or difference between peak and baseline > 60mmHg for men (>190 mmHg or 50 mmHg in women) (2). aTRH was defined as resting SBP above 140mmHg in the last ST despite simultaneous use of ≥3 different antihypertensive agents. The average time between STs was 4±3 years. The incidence of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, heart failure and stroke) were analyzed during the follow-up period of 10±3 years. Logistic and Cox regression models were used in time-to-event analysis. Data presented as: mean ± standard deviation; 95% confidence interval (CI) for odds ratios (OR); significance between groups p<0.05. Results The incidence of aTRH between STs was 15% (n=30), with 48% of them (n=14) receiving ≥4 or more antihypertensive drugs. aTRH vs non-aTRH were similar at baseline for sex (89% male, p=0.67), hypertension (HT, 62%,p=0.08), dyslipidemia (79%, p=0.86), smoke (46%, p=0.50), chronic kidney disease (13%, p=0.39), myocardial infarction (75%, p=0.39), heart failure (4.5%, p=0.40), but not for body mass index (30±3 vs 28±3 kg/m2, p=0.012) and diabetes (60.0 vs 28.6%, p=0.003) that were higher in the aTRH group. The average ePWV was 9.3±1.6 m/s (9.14±1.5 vs 10.2±1.7 m/s, non-aTRH vs aTRH p=0.001); 22.6% patients had HRE (20.4% vs 36.0%, non-aTRH vs aTRH, p=0.084). In contrast to HRE (adjusted OR=1.34, CI 0.4-4.3, p=0.62), ePWV was correlated with aTRH (adjusted OR=2.0, CI 1.1-4.1, p=0.024) after adjusting for age, comorbidities and anti-HT drugs, with an area under the ROC curve of 0.7 (CI 0.6-0.8). Both aTHR (OR=2.6, CI 1.2-5.8, p=0.017) and ePWV (adjusted OR=1.3, CI 1.2-5.8, p=0.024) were associated with MACE. Conclusion ePWV is a simple and robust marker that outperforms HRE in predicting aTRH and MACE in CAD patients. Higher ePWV values were independently associated with the incidence of aTRH. This study strengthens the importance of developing new strategies to control arterial stiffness in the treatment of RH and prevention of MACE.