Bedtime hypertension treatment increases ambulatory blood pressure control and reduces cardiovascular risk in resistant hypertension

The cross-sectional 24h ambulatory blood pressure (BP) monitoring (ABPM) study by de la Sierra et al. reported 37.5% incidence of isolated-office (“white-coat“) resistant hypertension (RH), defined as clinic BP ≥140/90 mmHg plus 24h BP mean <130/80 mmHg; it was even higher (44.1%) when defined by daytime BP mean <135/85 mmHg. This is markedly higher than the 17.4% estimate based on more reproducible 48h ABPM and defined as clinic BP ≥140/90 mmHg plus daytime and nighttime BP means of <135/85 mmHg and <120/70 mmHg, respectively. The findings of de la Sierra et al. might well be an overestimation, because: (i) among patients defined as “white-coat RH”, 34.4% ingested ≥4 hypertension medications/daily; by definition, treatment with >3 medications/daily is true RH, regardless of BP values; accordingly, inclusion of RH patients treated with ≥4 medications would decrease the prevalence of white-coat RH to 24.6%; (ii) RH is characterized by high prevalence of nocturnal hypertension and abnormal non-dipper BP pattern; current guidelines designate separate diagnostic thresholds for daytime and nighttime ABPM means; mean nighttime BP ≥120/70 mmHg should be considered hypertensive, regardless of mean daytime or clinic BP. The investigator-promoted, government-funded Hygia Project, designed to prospectively evaluate cardiovascular disease (CVD) risk in primary care centers of Northwest Spain using highly reproducible 48h ABPM, substantiates elevated sleep-time BP is highly prevalent in diabetes, chronic kidney disease, and RH, and significantly more frequent than elevated daytime BP. Furthermore, prevalence of isolated-office hypertension was up to three times higher when defined only by the daytime BP mean, than jointly by the daytime and nighttime BP means. Despite current recommendations, use of the 24h BP mean to diagnose isolated-office hypertension, as done by de la Sierra et al., is inadequate; a “normal” 24h BP mean is not a guarantee of a normal nighttime BP mean. Subjects with the same 24h BP mean might have a BP pattern ranging from extreme-dipping to rising (asleep BP mean > awake BP mean), with potentially markedly different CVD risk. Elevated sleep-time BP is a better predictor of CVD risk than awake or 24h BP means, and treatment-induced reduction of sleep-time BP in hypertension has been prospectively shown to be the most significant independent predictor of event-free survival. In conclusion, de la Sierra et al. cannot challenge findings from randomized, prospective clinical trials consistently reporting that bedtime ingestion of hypertension medications improves BP control and increases CVD event-free survival of RH patients.