Nocturnal BP Profile Predicts CPAP Effect on BP in Patients With OSA and Resistant Hypertension

BP physiologically drops by at least 10% during nighttime sleep compared with daytime values (normal dipping pattern). A disruption of such circadian BP rhythm, the so-called nondipping pattern, is associated with poorer cardiovascular outcomes.1Kario K. Hoshide S. Mizuno H. et al.JAMP Study GroupNighttime blood pressure phenotype and cardiovascular prognosis: practitioner-based nationwide JAMP study.Circulation. 2020; 142: 1810-1820Crossref PubMed Scopus (129) Google Scholar The lack of dipping can be influenced by many extrinsic and intrinsic factors (genetic, behavioral, and environmental factors; comorbidities; and treatments). Sleep disturbances, particularly OSA, are one of the most frequent causes of circadian BP rhythm disruption.2Huart J. Persu A. Lengelé J.P. Krzesinski J.M. Jouet F. Stergiou G. Pathophysiology of the nondipping blood pressure pattern.Hypertension. 2023; 80: 719-729Crossref PubMed Scopus (4) Google Scholar OSA is one of the causes of resistant hypertension (RH), defined as the lack of 24 h BP control despite the use of at least three antihypertensive drugs taken at maximally tolerated doses, one of which should be a diuretic.3Calhoun D.A. Jones D. Textor S. et al.Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.Hypertension. 2008; 51: 1403-1419Crossref PubMed Scopus (1286) Google Scholar More than 75% of patients with RH have concomitant OSA, and OSA treatment by means of CPAP can abolish respiratory events and reduce both 24 h systolic BP (SBP) and diastolic BP (DBP), especially during the night.4Labarca G. Schmidt A. Dreyse J. et al.Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): systematic review and meta-analysis.Sleep Med Rev. 2021; 58101446Crossref PubMed Scopus (48) Google Scholar In the largest ever randomized controlled trial on the effect of CPAP on BP in patients with RH, the Hipertensión Arterial Resistente Control con CPAP (HIPARCO) trial, a total of 194 patients with RH and OSA (apnea-hypopnea index [AHI] ≥ 15 events/h) were randomized to standard care and CPAP at optimal pressure (n = 98) or to standard care without CPAP (n = 96) for 3 months, without any changes in the antihypertensive treatment during the study. In an intention-to-treat analysis, the CPAP group achieved a significant decrease in both 24 h SBP and 24 h DBP of 4.2 mm Hg (95% CI, 0.4-8.0 mm Hg; P = .03) and 3.8 mm Hg (95% CI, 1.4-6.1 mm Hg; P = .002), respectively, adjusted to changes in the control group. Moreover, the percentage of patients displaying a normal nocturnal dipping BP pattern at the end of the study was greater in the CPAP group than in the control group (CPAP group, 35.9% vs control group, 21.6%; adjusted OR, 2.4; 95% CI, 1.2-5.1), with fewer patients in the CPAP group displaying a nocturnal riser pattern (ie, an increase in nighttime BP) at the end of the study, compared with the control group (adjusted OR, 0.45; 95% CI, 0.23-0.91).5Martínez-García M.A. Capote F. Campos-Rodríguez F. et al.Spanish Sleep NetworkEffect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial.JAMA. 2013; 310: 2407-2415Crossref PubMed Scopus (500) Google Scholar However, little is known about the potential role of the BP nocturnal pattern (dipping, nondipping, or riser) as a predictor of BP response to CPAP treatment in patients with OSA and RH. We analyzed the effect of CPAP treatment on 24 h SBP and 24 h DBP, using an intention-to-treat analysis (as we did in the HIPARCO trial)5Martínez-García M.A. Capote F. Campos-Rodríguez F. et al.Spanish Sleep NetworkEffect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial.JAMA. 2013; 310: 2407-2415Crossref PubMed Scopus (500) Google Scholar according to the BP nocturnal profile in patients enrolled in the HIPARCO trial. The results are presented as intergroup comparisons of the intragroup (baseline to end of follow-up) change in 24 h arterial BP assessed by analysis of covariance to adjust for clinically relevant covariates (24 h baseline BP level, age, sex, number of antihypertensive drugs, baseline AHI, and previous cardiovascular events). The statistical package Stata (StataCorp), version 11, was used for analysis. The general characteristics and treatments of the included patients have been published elsewhere5Martínez-García M.A. Capote F. Campos-Rodríguez F. et al.Spanish Sleep NetworkEffect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial.JAMA. 2013; 310: 2407-2415Crossref PubMed Scopus (500) Google Scholar: the mean age was 56 (SD 9.5) years, with 68.6% men. At baseline, the mean AHI was 40.4 (SD 19.8) events/h; the mean 24 h SBP and DBP were 144.2 (SD 12.5) and 83.0 (SD 10.5) mm Hg, respectively; and the mean nocturnal SBP and DBP were 141.2 (SD 15.8) and 78.5 (SD 12.4) mm Hg, respectively. There were no differences in the baseline 24 h SBP (142 [SD 12.9], 144.4 [SD 10.9], and 146.1 [SD 13.3] mm Hg; P = .23) and 24 h DBP (82.4 [SD 8.9], 83.9 [SD 10.7], and 82.3 [SD 11.4] mm Hg; P = .59) in the groups according to the nocturnal pattern (dipper, nondipper, and riser, respectively). The patients were taking an average 3.8 antihypertensive drugs, and 21.4% of them had experienced at least one previous cardiovascular event. Good adherence to CPAP (at least 4 h/d) was observed in 72.4% of patients. The average use of CPAP was 5 (SD 1.9) h/d, the mean titrated CPAP pressure was 8 (SD 2.1) mm Hg, and the residual AHI was 4.1 (SD 5.3) events/h. According to the definitions of the European Society of Hypertension Practice Guidelines for Office and Out-of-Office Blood Pressure Measurement,6Stergiou G.S. Palatini P. Parati G. et al.2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement.J Hypertens. 2021; 39: 1293-1302Crossref PubMed Scopus (296) Google Scholar the patients were divided according to their dipping status as follows: 50 (25.8%) participants with dips or extreme dips, 83 (42.8%) participants without dips, and 61 (31.4%) participants with a rising nocturnal SBP pattern. As observed in Table 1, both 24 h SBP and 24 h DBP were significantly reduced only in the CPAP-treated group with a nondipping or rising profile. Moreover, the more uncontrolled the nocturnal BP, the better the BP-lowering effect of CPAP after adjustment for confounders. The decrease in 24 h SBP in participants without dips or rising profiles was significantly greater than that observed for participants with dips (no dips vs dips, P = .012; and rising vs dips, P = .001). No differences were observed between participants with no dips and those with a rising profile. Regarding 24 h DBP, similar results were seen (no dips vs dips; P = .003; rising vs dips, P = .001, with no differences between participants with no dips and those with a rising profile). The P-trend values for 24 h SBP and 24 h DBP were statistically significant (P = .013 and P = .033, respectively).Table 1CPAP Effect on 24 h Systolic and Diastolic BP, Depending on the Nocturnal BP PatternNocturnal PatternControl (n = 96)CPAP (n = 98)AdjustedIntergroupDifference (95% CI)∗Results adjusted by 24 h baseline BP level, age, sex, number of antihypertensive drugs, baseline apnea-hypopnea index, and previous cardiovascular events.P ValueDifference in 24 h SBP (from baseline to follow-up BP) Dips (n = 50)1.48 (13.2)2.96 (10.9)1.51 (0.8-7.7).25 No dips (n = 83)–2.60 (12.7)2.60 (11.6)5.49 (1.7-8.5).012 Rising (n = 61)2.03 (11.7)8.30 (14.1)6.33 (1.2-6.9).001Difference in 24 h DBP (from baseline to follow-up BP) Dips (n = 50)0.67 (7.24)3.80 (6.95)3.23 (1.2-5.8).035 No dips (n = 83)–1.00 (9.23)3.36 (8.68)4.56 (1.4-6.1).003 Rising (n = 61)1.10 (6.81)5.80 (9.79)4.99 (1.6-5.9).001Positive values indicate a decrease in BP, and negative values indicate an increase in BP, from the baseline to the final values. Entries in boldface indicate statistical significance. SBP = systolic BP; DBP = diastolic BP.∗ Results adjusted by 24 h baseline BP level, age, sex, number of antihypertensive drugs, baseline apnea-hypopnea index, and previous cardiovascular events. Open table in a new tab Positive values indicate a decrease in BP, and negative values indicate an increase in BP, from the baseline to the final values. Entries in boldface indicate statistical significance. SBP = systolic BP; DBP = diastolic BP. Our study provides evidence that the various nocturnal BP pattern predicted changes in 24 h BP after CPAP treatment in patients with OSA and RH. In fact, on the basis of the data shown in Table 1, the reduction in 24 h BP levels from baseline to follow-up was only significant in participants with a rising profile and those with no dips but not in those with dips, after adjusting for confounders including baseline 24 h BP values. These results are of clinical relevance as they can help clinicians to make decisions when assessing patients with RH and OSA, particularly in the absence of excessive daytime sleepiness. These data are consistent and further extend the results of a systematic review and meta-analysis7Pengo M.F. Soranna D. Giontella A. et al.Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis.Eur Respir J. 2020; 551901945Crossref Scopus (84) Google Scholar in which BP at baseline was one of the main predictors of BP reduction in patients with OSA treated with CPAP. Most importantly, the results of the present analysis reinforce the importance of a more thorough assessment of the BP profile of patients with OSA by means of 24 h arterial BP monitoring, as proposed in a clinical framework,8Pengo M. Gozal D. Martinez-Garcia M.A. Should we treat with continuous positive airway pressure severe non-sleepy obstructive sleep apnea individuals without underlying cardiovascular disease?.Sleep. 2022; 45: zsac208Crossref PubMed Scopus (4) Google Scholar as well as in the joint recommendations by the European Society of Hypertension and the European Respiratory Society.9Parati G. Lombardi C. Hedner J. et al.European Respiratory SocietyEU COST ACTION B26 MembersPosition paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea.J Hypertens. 2012; 30: 633-646Crossref PubMed Scopus (169) Google Scholar Because not all patients respond equally to OSA treatment in terms of BP control, it is important to determine which phenotypes achieve better BP control with CPAP, to progress toward a more personalized treatment of OSA. Regarding patients with RH, an analysis of the HIPARCO trial showed that those with uncontrolled baseline BP and more severe OSA-related nocturnal hypoxia achieved a more consistent BP reduction with CPAP. However, the baseline BP pattern was not previously studied as a predictor of CPAP response in patients with RH and OSA.10Martinez-Garcia M.A. Pengo M. Clinical phenotype of resistant hypertension responders to continuous positive airway pressure treatment: results from the HIPARCO randomized clinical trial.Hypertension. 2021; 78: 559-561Crossref PubMed Scopus (3) Google Scholar The main limitation of our study is that some confounders associated with changes in BP patterns, such as diet, genetic factors, and BP treatment (dosage and time of day administered), were not assessed.1Kario K. Hoshide S. Mizuno H. et al.JAMP Study GroupNighttime blood pressure phenotype and cardiovascular prognosis: practitioner-based nationwide JAMP study.Circulation. 2020; 142: 1810-1820Crossref PubMed Scopus (129) Google Scholar Moreover, the sleep studies performed in the HIPARCO trial were attended cardiorespiratory poligraphies, and therefore we were not able to measure sleep fragmentation or other sleep disorders such as insomnia or leg movement during sleep. Furthermore, compared with the no dips and rising profile subgroups, the lower number of patients in the dips group could have obscured a statistically significant effect of CPAP in the adjusted intergroup comparison. Last, the low number of patients without nocturnal hypertension meant that we could not run an analysis comparing the effect of CPAP on nocturnal hypertension. Our results highlight the need to monitor BP profiles by means of 24 h arterial BP monitoring in patients with OSA, instead of relying only on office BP measurements, as nocturnal BP patterns may have an important predictive value with respect to the effect of CPAP treatment. In conclusion, the worse the pretreatment nocturnal BP control, the better the effect of CPAP in controlling 24 h BP in patients with RH and OSA. Compared with a control group, CPAP seems not effective in reducing 24 h SBP in RH with a nocturnal dipping pattern. The positive effect of CPAP on nocturnal BP patterns confers additional cardiovascular protection, independent of its effect on daytime BP levels.11Navarro-Soriano C. Martínez-García M.A. Torres G. et al.Spanish Sleep NetworkLong-term effect of CPAP treatment on cardiovascular events in patients with resistant hypertension and sleep apnea: data from the HIPARCO-2 study.Arch Bronconeumol (Engl Ed). 2021; 57: 165-171Crossref PubMed Google Scholar None declared.