Bioengineering and Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, Pontevedra, Spain.
Chronobiol Int. 2013 Mar;30(1-2):328-39. doi: 10.3109/07420528.2012.701885. Epub 2012 Oct 25.
Several previous studies found that too great a reduction of clinic blood pressure (BP) by treatment increased cardiovascular disease (CVD) risk, whereas moderate reduction decreased it. Thus, it has been suggested that the relationship between BP and CVD events is J-shaped, with CVD risk decreasing as BP is lowered, and then rising as BP is further decreased. Correlation between BP level and CVD risk, however, is stronger for ambulatory BP monitoring (ABPM) than clinical BP measurements. We previously established that the hypertension treatment-time regimen, upon awakening versus at bedtime, exerts differential effect on BP control during the day and nighttime, which translates into a differential degree of CVD risk prevention. We, therefore, investigated the role of hypertension treatment-time scheme on the nature of the relationship between achieved clinic and ambulatory BP and CVD risk in the MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares, i.e., Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events) study, a prospective, open-label, blinded-endpoint trial on 2156 hypertensive patients (1044 men/1112 women), 55.6 ± 13.6 (mean ± SD) yrs of age, randomized to ingest all prescribed once-a-day hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime. Ambulatory BP was measured for 48-h at baseline and annually thereafter, and more frequently (quarterly) when adjustment of treatment was necessary. After a median follow-up of 5.6 yrs, a J-shaped relationship was detected between total CVD events and clinic as well as awake BP mean, but only for the group of patients ingesting all medications upon awakening. The relationship was different in the group of patients who ingested ≥1 medications at bedtime; the risk of CVD events progressively diminished in a linear, rather than J-shaped, manner with treatment-induced decrease in awake BP mean. The adjusted hazard ratio of CVD events was significantly lower with the progressive reduction in the asleep BP mean, independent of the hypertension treatment-time regimen. There was no single major event, i.e., CVD death, myocardial infarction, or stroke, in patients who achieved an asleep systolic BP mean <103 mm Hg. Our findings indicate that bedtime hypertension treatment is not associated with a J-shaped relationship between achieved BP and CVD risk. The decreased CVD risk associated with the progressive reduction in asleep BP, more feasible by bedtime than morning hypertension treatment, has clinical implications, in particular, the need to consider the proper timing of hypertension medications, in conjunction with ABPM for proper assessment of BP control, as an improved and potentially safer means of reducing CVD risk of hypertensive patients.
先前有几项研究发现，治疗时过度降低诊所血压（BP）会增加心血管疾病（CVD）风险，而适度降低则会降低风险。因此，有人提出 BP 与 CVD 事件之间的关系呈 J 形，随着 BP 的降低，CVD 风险降低，而随着 BP 的进一步降低，CVD 风险又升高。然而，与临床 BP 测量相比，动态血压监测（ABPM）与 BP 水平和 CVD 风险之间的相关性更强。我们之前已经确定，醒来时与睡前相比，高血压治疗时间方案对日间和夜间的 BP 控制有不同的影响，这转化为 CVD 风险预防的不同程度。因此，我们在 MAPEC（Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events，即用于预测心血管事件的动态血压监测）研究中研究了高血压治疗时间方案对实现诊所和动态血压与 CVD 风险之间关系的性质的作用，这是一项前瞻性、开放标签、盲终点试验，涉及 2156 名高血压患者（1044 名男性/1112 名女性），年龄 55.6±13.6（均值±标准差），随机分为两组，一组在醒来时服用所有规定的每日一次的降压药物，另一组在睡前服用≥1 种药物的全部日剂量。在基线时进行了为期 48 小时的动态血压测量，此后每年进行一次，当需要调整治疗时则更频繁（每季度一次）。中位随访 5.6 年后，发现总 CVD 事件与诊所和清醒时 BP 平均值之间呈 J 形关系，但仅在醒来时服用所有药物的患者组中发现。在睡前服用≥1 种药物的患者组中，这种关系则不同；随着清醒时 BP 平均值的治疗诱导降低，CVD 事件的风险以线性而非 J 形方式逐渐降低。与高血压治疗时间方案无关，随着入睡时 BP 平均值的逐渐降低，CVD 事件的调整风险比显著降低。在实现入睡时收缩压平均值<103mmHg 的患者中，没有发生单一主要事件，即 CVD 死亡、心肌梗死或中风。我们的研究结果表明，睡前高血压治疗与已实现的 BP 与 CVD 风险之间的 J 形关系无关。与渐进性降低入睡时 BP 相关的降低 CVD 风险，通过睡前而非清晨的高血压治疗更可行，具有临床意义，特别是需要考虑高血压药物的适当时机，结合 ABPM 以适当评估 BP 控制，作为降低高血压患者 CVD 风险的一种改进且潜在更安全的手段。
