参考文献/References:
样本大小及类型 结局 研究类型 主要发现 Ohkubo等[4] 1 542例，一般人群 全因死亡 前瞻性（5年） 超杓型血压患者（61岁）与杓型血压患者无显著差异 Hoshide等[26] 811例，老年高血压患者 脑卒中 回顾性（3.4年） 在用药组[（71.0±9.7）岁]与未用药组[（70±8.5）岁]，超杓型血压患者的脑梗死发生率均高于杓型血压患者 Kario等[27] 575例，老年高血压患者 脑卒中 前瞻性（41个月） 超杓型血压患者[（70.0±9.2）岁]的脑卒中发生率高于杓型血压患者 Metoki等[28] 1 430例，一般人群 脑卒中 前瞻性（10年） 超杓型血压患者[（61.1±10.6）岁]的脑卒中发生率高于杓型血压患者 Bastos等[15] 1 200例，已接受/未经治疗的高血压患者 CVEs 前瞻性（8.2年） 超杓型血压患者[（51.1±12.7）岁]与杓型血压患者无显著差异 Lo等[11] 1 199例，已接受/未经治疗的高血压患者 CVEs及全因死亡 回顾性（6.4年） 超杓型血压患者[（63.8±8.7）岁]与杓型血压患者无显著差异 Muxfeldt等[29] 556例，难治性高血压患者 CVEs 前瞻性（4.8年） 超杓型血压患者[（61.1±11.7）岁]与杓型血压患者无显著差异 Cardoso等[30] 1 726例，难治性高血压患者 CVEs 前瞻性（8.3年） 超杓型血压患者[（58.3±11.0）岁]与杓型血压患者无显著差异 Fagard等[31] 3 468例，已接受/未经治疗的高血压患者 CVEs 荟萃分析 超杓型血压患者[（63.2±11.1）岁]与杓型血压患者无显著差异 Palatini等[8] 10 868例，已接受/未经治疗的高血压患者 CVEs 回顾性（5.7年） 在年龄≥70岁的患者中，超杓型血压患者相比杓型血压患者CVEs风险显著增加（70岁以下超杓型血压患者与CVEs风险增加无关） Ishikawa等[32] 811例，老年高血压患者 CVEs 前瞻性（20个月） 超杓型血压患者（67～71岁）发生脑卒中及心肌梗死的风险高于杓型血压患者 注：CVEs，心血管事件。
Hoshide等[26]为了探究降压治疗的益处与血压昼夜模式之间的关系，对811例老年高血压患者进行了动态血压监测，随访期平均41个月。该研究结果显示，超杓型血压患者的脑梗死发生率为12%（用药组）和13%（未用药组），高于杓型血压患者的脑梗死发生率（用药组4.7%，未用药组8.8%）。Kario等[27]在575例老年高血压患者中分析了血压昼夜模式与脑血管疾病之间的关系，发现53%的超杓型血压患者存在无症状性脑梗死。随后的随访研究发现超杓型血压患者发生卒中事件的比例（12%）显著高于杓型血压患者（6.1%）。此外，Metoki等[28]基于Ohasama研究发现10年随访中夜间血压下降幅度20%的患者发生脑出血的风险高于下降幅度＜20%的患者[HR=2.69(95% CI 1.14～6.36)，P=0.02]。这表明与超杓型血压相关的夜间脑灌注不足很可能是脑卒中发生的危险因素。
关于超杓型血压与心血管事件（cardiovascular events，CVEs）之间的关系，Bastos等[15]前瞻性研究（平均随访时间8.2年）发现，在4种血压昼夜模式中，超杓型血压的CVEs发生率（9.8%）最低。最近的一项针对1 199例中国高血压患者的回顾性研究[11]（平均6.4年）显示超杓型血压患者的心血管预后与杓型血压患者之间无显著差异（P=0.975），Muxfeldt等[29]与Cardoso等[30]对难治性高血压患者进行的前瞻性研究亦得到类似结果。此外，一项荟萃分析[31]纳入在欧洲进行的4项前瞻性研究中的3 468例高血压患者的数据，该分析结果亦显示超杓型血压患者的CVEs发生率与杓型血压患者无显著差异。但以上研究均未在不同年龄中进行亚组分析。Palatini等[8]对不同年龄段超杓型血压患者与CVEs的相关性进行了分析，研究结果显示在70岁以下的人群中，与杓型血压患者相比，超杓型血压患者并未表现出较差的预后[HR=0.99(95% CI 0.73～1.34)，P=0.93]。然而，70岁以上的受试者风险显著增加[HR=1.88(95% CI 1.14～3.11)，P=0.013]。Ishikawa等[32]对811例伴或不伴CKD的老年高血压患者[平均年龄分别为（67.4±8.3）岁和（71.8±9.6）岁]进行的一项前瞻性研究发现，超杓型血压模式是CVEs的独立危险因素，这从侧面印证了Palatini等的研究结果。超杓型血压模式与CVEs之间的关系尚存在争议，但在70岁以上的老年人群中，似乎应着重看待超杓型血压，其很有可能会增加CVEs的发生风险。
3 血压昼夜节律异常的可能机制
血压昼夜节律由生物钟调控，包括中枢和外周生物钟，这些生物钟因食物和光线的提示而同步，并通过激素及神经信号进行交流[33]。生物钟的核心调节基因包括BMAL1、CLOCK、PER、CRY和REV-ERB等[34]。在哺乳动物中，BMAL1和CLOCK在昼夜节律机制中起正反馈作用，它们驱动PER、CRY和REV-ERB等基因的表达，而PER、CRY和REV-ERB等基因则对BMAL1和CLOCK基因的表达起负反馈作用，这一反馈机制可能是大多数生理功能昼夜变化的基础[35]。如机体生物钟的核心调节基因发生变化，血压昼夜节律则会发生异常改变，从而导致多种疾病的发生[36-37]。
夜间睡眠时，交感神经活性下降，体内去甲肾上腺素和肾上腺素水平会降至每日最低点，进而降低心输出量和外周血管阻力，引发夜间血压下降[38-39]。此外肠道菌群的不同亦会导致昼夜血压的变化[40]。总体而言，血压昼夜节律的产生是一个复杂现象，是由多种生理机制相互作用所导致，且夜间血压下降程度与多种因素相关。
4 小结
随着诊断标准及研究人群临床特征的不同，超杓型血压的流行病学数据存在差异，结合目前研究，其在一般人群中所占比例不低，对这部分人群仍需大样本的前瞻性研究来探究超杓型血压对一般人群的影响。此外，目前大多数关于血压昼夜模式与HMOD关联的研究未能找到一致的结果来支持超杓型血压会对心脏结构及功能、血管、肾脏等产生不利影响。但就主要不良事件而言，现有的数据表明夜间血压的剧烈下降可能导致大脑低灌流，从而导致脑血管意外事件的发生，但这种机制不适用于年轻、无并发症的高血压患者。另外70岁以上的超杓型血压患者应受到临床医生的关注，因为超杓型血压很有可能增加CVEs发生风险。总之，应对超杓型血压进行深入研究，探讨其相关机制，进一步探索纠正异常血压昼夜模式的临床意义，从而为异常血压昼夜模式的防治提供更多证据。
[1] Habas E Sr,Akbar RA,Alfitori G,et al. Effects of nondipping blood pressure changes:a nephrologist prospect[J]. Cureus,2023,15(7):e42681.
[2] Birmingham WC,Jorgensen A,Hancock S,et al. Social support:the effect on nocturnal blood pressure dipping[J]. Int J Environ Res Public Health,2023,20(5):4579.
[3] Dahle N,?rnl?v J,Leppert J,et al. Nondipping blood pressure pattern predicts cardiovascular events and mortality in patients with atherosclerotic peripheral vascular disease[J]. Vasc Med,2023,28(4):274-281.
[4] Ohkubo T,Imai Y,Tsuji I,et al. Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study[J]. Am J Hypertens,1997,10(11):1201-1207.
[5] Terracciano A,Strait J,Scuteri A,et al. Personality traits and circadian blood pressure patterns:a 7-year prospective study[J]. Psychosom Med,2014,76(3):237-243.
[6] Cuspidi C,Facchetti R,Quarti-Trevano F,et al. Clinical correlates and subclinical cardiac organ damage in different extreme dipping patterns[J]. J Hypertens,2020,38(5):858-863.
[7] Tadic M,Cuspidi C,Majstorovic A,et al. The association between 24-h blood pressure patterns and left ventricular mechanics[J]. J Hypertens,2020,38(2):282-288.
[8] Palatini P,Verdecchia P,Beilin LJ,et al. Association of extreme nocturnal dipping with cardiovascular events strongly depends on age[J]. Hypertension,2020,75(2):324-330.
[9] Triantafyllidi H,Birmpa D,Schoinas A,et al. Is there any true distinction in extreme dipping versus nondipping or dipping phenotype regarding hypertension-mediated organ damage in newly diagnosed and never-treated hypertensive patients?[J]. J Hum Hypertens,2022,36(1):51-60.
[10] Cuspidi C,Caffi G,Dell’Oro R,et al. Extreme dipping:always means nocturnal hypotension?[J]. Am J Hypertens,2019,32(9):842-847.
[11] Lo L,Hung SWS,Chan SSW,et al. Prognostic value of nocturnal blood pressure dipping on cardiovascular outcomes in Chinese patients with hypertension in primary care[J]. J Clin Hypertens(Greenwich),2021,23(7):1291-1299.
[12] Cho SMJ,Lee H,Yoo TH,et al. Association between nocturnal blood pressure dipping and chronic kidney disease among patients with controlled office blood pressure[J]. Am J Hypertens,2021,34(8):821-830.
[13] Ivanovic BA,Tadic MV,Celic VP. To dip or not to dip? The unique relationship between different blood pressure patterns and cardiac function and structure[J]. J Hum Hypertens,2013,27(1):62-70.
[14] Kario K,Eguchi K,Nakagawa Y,et al. Relationship between extreme dippers and orthostatic hypertension in elderly hypertensive patients[J]. Hypertension,1998,31(1):77-82.
[15] Bastos JM,Bertoquini S,Polónia J. Prognostic value of subdivisions of nighttime blood pressure fall in hypertensives followed up for 8.2 years. Does nondipping classification need to be redefined?[J]. J Clin Hypertens(Greenwich),2010,12(7):508-515.
[16] Woodiwiss AJ,Libhaber CD,Sareli P,et al. Impact of blunted nocturnal blood pressure dipping on cardiac systolic function in community participants not receiving antihypertensive therapy[J]. Am J Hypertens,2018,31(9):1002-1012.
[17] Rodrigues JCL,Amadu AM,Ghosh Dastidar A,et al. Noctural dipping status and left ventricular hypertrophy:a cardiac magnetic resonance imaging study[J]. J Clin Hypertens(Greenwich),2018,20(4):784-793.
[18] Cuspidi C,Tadic M,Sala C,et al. Extreme dipping:is the cardiovascular risk increased? An unsolved issue[J]. J Hypertens,2019,37(10):1917-1926.
[19] Jerrard-Dunne P,Mahmud A,Feely J. Circadian blood pressure variation:relationship between dipper status and measures of arterial stiffness[J]. J Hypertens,2007,25(6):1233-1239.
[20] Amah G,Ouardani R,Pasteur-Rousseau A,et al. Extreme-dipper profile,increased aortic stiffness,and impaired subendocardial viability in hypertension[J]. Am J Hypertens,2017,30(4):417-426.
[21] García-Ortiz L,Gómez-Marcos MA,Martín-Moreiras J,et al. Pulse pressure and nocturnal fall in blood pressure are predictors of vascular,cardiac and renal target organ damage in hypertensive patients(LOD-RISK study)[J]. Blood Press Monit,2009,14(4):145-151.
[22] Marinakis AG,Vyssoulis GP,Michaelides AP,et al. Impact of abnormal nocturnal blood pressure fall on vascular function[J]. Am J Hypertens,2003,16(3):209-213.
[23] Park CH,Jhee JH,Chun KH,et al. Nocturnal systolic blood pressure dipping and progression of chronic kidney disease[J]. Hypertens Res,2023,47(1):215-224.
[24] Duarte T,Gon?alves S,Brito R,et al. Relationship between nocturnal blood pressure profiles and the presence and severity of hypertensive retinopathy[J]. Rev Port Cardiol(Engl Ed),2018,37(2):169-173.
[25] Bowe A,Grünig M,Schubert J,et al. Circadian variation in arterial blood pressure and glaucomatous optic neuropathy—A systematic review and meta-analysis[J]. Am J Hypertens,2015,28(9):1077-1082.
[26] Hoshide Y,Kario K,Schwartz JE,et al. Incomplete benefit of antihypertensive therapy on stroke reduction in older hypertensives with abnormal nocturnal blood pressure dipping(extreme-dippers and reverse-dippers)[J]. Am J Hypertens,2002,15(10 Pt 1):844-850.
[27] Kario K,Pickering TG,Matsuo T,et al. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives[J]. Hypertension,2001,38(4):852-857.
[28] Metoki H,Ohkubo T,Kikuya M,et al. Prognostic significance for stroke of a morning pressor surge and a nocturnal blood pressure decline:the Ohasama study[J]. Hypertension,2006,47(2):149-154.
[29] Muxfeldt ES,Cardoso CR,Salles GF. Prognostic value of nocturnal blood pressure reduction in resistant hypertension[J]. Arch Intern Med,2009,169(9):874-880.
[30] Cardoso CRL,Salles GF. Associations of the nocturnal blood pressure fall and morning surge with cardiovascular events and mortality in individuals with resistant hypertension[J]. J Hypertens,2021,39(6):1177-1187.
[31] Fagard RH,Thijs L,Staessen JA,et al. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension[J]. J Hum Hypertens,2009,23(10):645-653.
[32] Ishikawa J,Shimizu M,Hoshide S,et al. Cardiovascular risks of dipping status and chronic kidney disease in elderly Japanese hypertensive patients[J]. J Clin Hypertens(Greenwich),2008,10(10):787-794.
[33] Mitchell JW,Gillette MU. Development of circadian neurovascular function and its implications[J]. Front Neurosci,2023,17:1196606.
[34] BaHammam AS,Pirzada A. Timing matters:the interplay between early mealtime,circadian rhythms,gene expression,circadian hormones,and metabolism—A narrative review[J]. Clocks Sleep,2023,5(3):507-535.
[35] Shafer BM,Kogan SA,McHill AW. Pressure building against the clock:the impact of circadian misalignment on blood pressure[J]. Curr Hypertens Rep,2023,26(1):31-42.
[36] Fan R,Peng X,Xie L,et al. Importance of Bmal1 in Alzheimer’s disease and associated aging-related diseases:mechanisms and interventions[J]. Aging Cell,2022,21(10):e13704.
[37] Zheng Y,Pan L,Wang F,et al. Neural function of Bmal1:an overview[J]. Cell Biosci,2023,13(1):1.
[38] Toffoli B,Tonon F,Giudici F,et al. Preliminary study on the effect of a night shift on blood pressure and clock gene expression[J]. Int J Mol Sci,2023,24(11):9309.
[39] Ko YE,Jhee JH. Short-term blood pressure variability as a potential therapeutic target for kidney disease[J]. Clin Hypertens,2023,29(1):23.
[40] Huart J,Persu A,Lengelé JP,et al. Pathophysiology of the nondipping blood pressure pattern[J]. Hypertension,2023,80(4):719-729.
相似文献/References:
[1]孙刚,黄冠华,综述.高血压合并心力衰竭的治疗策略[J].心血管病学进展,2016,(2):201.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.027]
SUN Gang,HUANG Guanhua.Treatment Strategy of Hypertension with Heart Failure[J].Advances in Cardiovascular Diseases,2016,(5):201.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.027]
[2]范贵娟,综述,徐瑞,等.盐敏感性高血压的研究进展[J].心血管病学进展,2016,(4):364.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.010]
FAN Guijuan,XU Rui.Research Progress of Salt Sensitive Hypertension[J].Advances in Cardiovascular Diseases,2016,(5):364.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.010]
[3]陈源源.钙通道阻滞剂在降压治疗中的应用[J].心血管病学进展,2015,(6):662.[doi:10.3969/j.issn.1004-3934.2015.06.002]
CHEN Yuanyuan.Application of Calcium Channel Blockers in Hypertension Treatment[J].Advances in Cardiovascular Diseases,2015,(5):662.[doi:10.3969/j.issn.1004-3934.2015.06.002]
[4]张瑞 毛露 孙硕 Dirk Hermann 陈艾东.内皮素-1干预成为高血压治疗新靶点的展望[J].心血管病学进展,2019,(7):969.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.000]
ZHANG Rui MAO LuSUN ShuoDIRK Hermann CHEN Aidong.The Prospect of Endothelin-1 Intervention as A New Target for the Treatment of Hypertension[J].Advances in Cardiovascular Diseases,2019,(5):969.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.000]
[5]张毅,柳志红.动态血压监测在高血压中的应用现状与问题[J].心血管病学进展,2019,(6):848.[doi:10.16806/j.cnki.issn.1004-3934.2019.06.003]
ZHANG Yi,LIU Zhihong.Current status and nsolved Pproblems of Ambulatory Blood Pressure Monitoring for the Management of Hypertension[J].Advances in Cardiovascular Diseases,2019,(5):848.[doi:10.16806/j.cnki.issn.1004-3934.2019.06.003]
[6]黄秋瑾 胡蓉.高血压合并糖尿病患者血压控制率和控制目标的探讨[J].心血管病学进展,2019,(7):973.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.002]
HUANG QiujinHU Rong.Discussion on Blood Pressure Control Rate and Control Target in Patients with Hypertension Complicated with Diabetes[J].Advances in Cardiovascular Diseases,2019,(5):973.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.002]
[7]张旭明 王曦.高血压对认知功能的影响[J].心血管病学进展,2019,(7):977.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.003]
ZHANG Xuming,WANG Xi.The Relationship Between Hypertension and Cognitive Function[J].Advances in Cardiovascular Diseases,2019,(5):977.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.003]
[8]凌梦军 陈明凌梦军.阻塞性睡眠呼吸暂停低通气综合征与高血压关系的研究进展[J].心血管病学进展,2019,(5):722.[doi:10.16806/j.cnki.issn.1004-3934.2019.05.015]
[9]李波 郭毅 田进文 邓珏琳.高血压合并2型糖尿病的治疗进展[J].心血管病学进展,2019,(9):1196.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.002]
LI Bo,GUO Yi,TIAN Jinwen,et al.Therapy in Hypertensive Patients with Type 2 Diabetes Mellitus[J].Advances in Cardiovascular Diseases,2019,(5):1196.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.002]
[10]王继航 赵施皓 李开亮 田进文 李玉龙 付士辉 沈明志 邓珏琳.远程医疗在高血压病管理中的研究进展[J].心血管病学进展,2019,(9):1199.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.003]
WANG Jihang,ZHAO Shihao,LI Kailiang,et al.Telemedicine in Hypertension Management[J].Advances in Cardiovascular Diseases,2019,(5):1199.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.003]