Matthew Walters 英国格拉斯哥大学
Treatment of blood pressure is among the most important interventions in the prevention of cardiovascular disease. Reduction of absolute levels of blood pressure has, historically, been the goal treatment. However, in recent years, new data has prompted a re-evaluation of the mechanistic basis of blood-pressure induced cardiovascular disease, and a re-consideration of optimal treatment strategies.
In a series of recent papers, the Oxford group, led by Professor Peter Rothwell, have explored the importance of blood pressure variability and its effect on cardiovascular outcomes, particularly stroke. In post-hoc analyses of randomised trials, the visit-to-visit variability of systolic blood pressure was highly predictive of stroke and other vascular events. Significantly this relationship was found to be independent of the conventional therapeutic target of mean blood pressure. Further, the analyses suggest that calcium-channel blockers reduce variability to a greater extent than other antihypertensive agents and that the improvement in variability seen with these agents may explain the reduced risk of stroke observed in recipients of these agents in large clinical trials. These observations have rekindled interest in the prognostic significance of blood pressure variability and in its potential as a new therapeutic target in the prevention of cardiovascular disease. Earlier work in this area had largely been confined to measure of short-term variability using indices derived from ambulatory monitoring. The prognostic information yielded by analysis of long-term visit-to-visit variability in office measurements had not previously been subjected to detailed scrutiny.
This new appreciation of long-term variability as a potential marker of risk should be reflected in the design and conduct of future clinical trials further validation of the concept is required in other datasets, as is a greater understanding of the mechanisms of blood pressure variability. Similarly, more information on the effects of different classes of antihypertensive drugs on variability is required, as is a more detailed exposition of the relative contribution of variability to the development of surrogate markers of risk such as arterial stiffness and left ventricular hypertrophy, and to the risk of different stroke subtypes.
Whether clinicians in everyday practice need to take account of these new observations is more questionable. The measurement of variability during secondary analyses of clinical trial datasets is easy, but far less readily achieved in the clinic. If further prospective work validates the new variability hypothesis, its implementation will be challenging. At present we lack the infrastructure to record and calculate these indices, and it may be that a further challenge to researchers will be the development of a more readily applicable measure of variability which may be used to inform treatment decisions.
Finally, on a more philosophical note, the hypertension community may wish to reflect on the need for new blood pressure targets. Our best evidence suggests that despite decades of awareness of the benefit of reduction in absolute levels of blood pressure, a disappointingly high proportion of hypertensive individuals remain sub-optimally controlled. The development of a new target will not help us bridge the already wide evidence-practice gap. This remains the single greatest challenge facing clinicians treating hypertensive patients in the 21st century.
核心观点
1.多项随机试验事后分析显示:随访间的血压变异性能够很好的预测卒中和其他血管事件,且该作用独立于平均血压水平。
2.钙通道阻滞剂(CCB)在卒中预防中具有明显优势,而与之伴随的则是其在降低血压变异性方面的明显优势。
3.长期血压变异性作为心脑血管疾病预测指标,在未来临床试验设计及实施中应有所体现。但是,目前应用于临床还存在诸多困难,如缺乏记录和统计血压变异性的工具。