Long-term Effect of CPAP Treatment on Cardiovascular Events in Patients With Resistant Hypertension and Sleep Apnea. Data From the HIPARCO-2 Study.

BACKGROUND: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE. METHODS: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3-6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP. RESULTS: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96-2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07-15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2-11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05-1.02; p=0.053). CONCLUSIONS: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events.

The HIPARCO-2 study: long-term effect of continuous positive airway pressure on blood pressure in patients with resistant hypertension: a multicenter prospective study.

INTRODUCTION: Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension. METHODS: The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up. RESULTS: Patients were followed up within 59 months [interquartile range (IQR): 44-70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [-3.9 mmHg; 95% confidence interval (CI): -8.1 to 0.3] and diastolic pressure (-3.5 mmHg [95% [CI]: -6.4-0.5]), with a higher magnitude during the night (-5.5 and -4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01). CONCLUSION: Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.

Factors associated with the changes from a resistant to a refractory phenotype in hypertensive patients: a Pragmatic Longitudinal Study.

Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01-1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42-1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01-1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47-7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.