高血压患者血压近日节律特点分析及其与靶器官损害的相关性研究
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摘要
目的：通过分析高血压患者血压近日节律特点,探讨高血压与血压近日节律特点之间的关系。通过分析合并靶器官损害的高血压患者血压近日节律特点,探讨靶器官损害发生、发展与血压近日节律特点之间的关系,为高血压患者判断预后和高血压的时间治疗学提供相关参考。方法：收集2009年5月至2009年11月在宜宾市第二人民医院心内科住院的早期轻、中度高血压患者和体检中心部分体检者共109例的24h动态血压、心率数据和一般临床资料(包括身高、体重、既往病史、吸烟史、生化检查、心脏彩超检查、颈动脉彩超检查、24h尿蛋白定量检查、心电图检查)。首先,使用时间生物学奠基人Halberg创立的单一余弦法对每一研究对象连续记录的24h动态血压、心率数据进行近日节律分析。然后根据中国高血压防治指南2005年修订版高血压诊断标准和1999年中国高血压防治指南建议的24h动态血压(ABPM)高血压诊断标准将所有研究对象分为高血压组(HP)72例和正常对照组(NM)37例。使用时间生物学奠基人Halberg创立的群体平均余弦法分别对高血压组和正常对照组24h动态血压、心率数据进行近日节律分析并作统计学处理。最后,根据第七版内科学用于危险分层的靶器官损害标准将高血压组分为高血压合并靶器官损害组(HPTD)42例和高血压未合并靶器官损害组(HPN)30例。使用时间生物学奠基人Halberg创立的群体平均余弦法对高血压合并靶器官损害组、高血压未合并靶器官损害组、正常对照组的24h动态血压、心率数据进行近日节律分析并作统计学处理。结果：1.明尼苏达单一余弦分析结果：所有研究对象24h收缩压、舒张压、心率变化均表现出明显的近日节律(P<0.05)。2.高血压组与正常对照组群体平均余弦分析结果：收缩压群体平均余弦分析结果表明高血压组和正常对照组收缩压整体近日节律存在(P<0.05),高血压组调整中值明显高于正常对照组(P<0.01),振幅明显低于正常对照组(P<0.05)；舒张压群体平均余弦分析结果表明二组人群舒张压整体近日节律存在(P<0.01),高血压组调整中值明显高于正常对照组(P<0.01),振幅与正常对照组无明显差异(P>0.05)；心率群体平均余弦分析结果表明二组人群心率整体近日节律存在(P<0.01),高血压组调整中值明显高于正常对照组(P<0.05),振幅明显低于正常对照组(P<0.05)。3.高血压合并靶器官损害组、高血压未合并靶器官损害组、正常对照组群体余弦分析结果：收缩压群体平均余弦分析结果表明高血压合并靶器官损害组收缩压整体近日节律消失(p>0.05),高血压未合并靶器官损害组、正常对照组收缩压整体近日节律存在(P<0.05)；高血压合并靶器官损害组、高血压未合并靶器官损害组调整中值明显高于正常对照组(P<0.01),高血压合并靶器官损害组振幅明显低于正常对照组(P<0.05),高血压未合并靶器官损害组振幅与正常对照组无明显差异(P>0.05),高血压合并靶器官损害组与高血压未合并靶器官损害组间调整中值、振幅无明显差异(P>0.05)；舒张压群体余弦分析结果表明三组人群舒张压整体近日节律均存在(p<0.05),高血压合并靶器官损害组、高血压未合并靶器官损害组调整中值明显高于正常对照组(P<0.01),高血压合并靶器官损害组振幅明显低于正常对照组(P<0.05)；高血压未合并靶器官损害组振幅与正常对照组无明显差异(P>0.05),高血压合并靶器官损害组与高血压未合并靶器官损害组间调整中值、振幅无明显差异(P>0.05)；心率群体余弦分析结果表明三组人群心率整体近日节律均存在(P<0.05),高血压合并靶器官损害组、高血压未合并靶器官损害组调整中值明显高于正常对照组(P<0.05),高血压合并靶器官损害组振幅明显低于正常对照组(P<0.05),高血压未合并靶器官损害组振幅与正常对照组无明显差异(P>0.05),高血压合并靶器官损害组与高血压未合并靶器官损害组间调整中值、振幅无明显差异(P>0.05)。
结论：1.高血压患者与正常血压患者24h收缩压、舒张压、心率变化均呈明显的近日节律。2.与正常血压者比较,未服用降压药物或停用降压药物的早期轻、中高血压患者血压、心率近日节律特点表现为收缩压、舒张压、心率调整中值升高,收缩压、心率振幅下降。3.高血压患者靶器官损害的发生、发展与血压、心率近日节律改变的发生明显相关,与正常血压者比较,合并靶器官损害的高血压患者血压、心率近日节律特点表现为收缩压整体近日节律消失,收缩压、舒张压、心率的调整中值升高和振幅下降；4.了解高血压患者近日节律特点可以为高血压患者判断预后以及高血压的时间治疗学提供一定参考价值。
Objective:By analyze the circadian rhythm characteristics of blood pressure in hypertensions, discuss the relations between hypertension and the circadian rhythm characteristics of blood pressure. By analyze the circadian rhythm characteristics of blood pressure in hypertensions with tatget organ damage, discuss the relations between the occur and development of target organ damage and blood pressure circadian rhythm characteristics. Provide some valuable reference for hypertension in prognosis s diagnosis and chronotherapy. Methods:This research has collected 24h ambulatory blood pressure data and general clinical information data (including height, weight, past medical history, smoking history, biochemical tests, echocardiography examination, carotid ultrasonography examination,24h urine protein examination, ECG) of 109 cases who were early hypertions degreed 1 or 2 in Department of Cardiology and Department of Physical examination, the second People Hospital of Yibin, First of all, using Single cosinor created by Halberg, the founder of Chronobiology, to study the data of each 24h ambulatory blood pressure, heart rate. Then according to the hypertension'diagnostic criteria in hypertension guidance in China in 2005 and the hypertension'diagnostic criteria of 24h ambulatory blood pressure (ABPM) in hypertension guidance in China in 1999, all subjects were divided into hypertensive (HP) 72 cases and normal control (NM) 37 cases. Using the Population mean cosinor created by Halberg, the founder of Chronobiology, to study the data of 24h ambulatory blood pressure, heart rate of hypertension group and normal control group. Finally, according to the diagnostic criteria of target organ damage, hypertension group was divided into the hypertension with target organ damage group (HPTD) 42 cases and hypertension not with target organ damage group (HPN) 30 cases. Using the Population mean cosinor created by Halberg, the founder of Chronobiology, to study the data of 24h ambulatory blood pressure, heart rate of hypertension with target organ damage group and hypertension not with target organ damage and normal control group. Results:1. Minnesota single cosine analysis:all subjects 24-hour systolic blood pressure, diastolic blood pressure, heart rate showed a significant circadian rhythm (P<0.05).2. the results of hypertensive groups and normal control group'population mean cosinor analysis:sistolic blood pressure population mean cosinor analysis showed that the hypertension group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.05), hypertension was significantly higher than the control group in mesor (P<0.01), the amplitude was significantly lower than the control group (P<0.05); diastolic blood pressure population mean cosinor analysis showed that the hypertension group and normal control group' systolic blood pressure whole circadian rhythm is existed (P<0.01), hypertension group was significantly higher than the normal control group in mesor (P<0.01), the amplitude is no significant difference than the normal control group (P>0.05); heart rate population mean cosinor analysis showed that the hypertension group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.01), hypertension group was significantly higher than the normal control group in mesor (P<0.05), the amplitude was significantly lower than the control group (P<0.05).3. the results of hypertensive with target organ damage groups and hypertension not with target organ damage groups and normal control group'population mean cosinor analysis:sistolic blood pressure population mean cosinor analysis showed that the hypertension with target organ group'systolic blood pressure whole circadian rhythm is not existed (p>0.05), hypertension not with target organ damage group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.05); hypertension with target organ damage group and hypertension not with target organ damage group was significantly higher the normal control group in mesor (P<0.01), hypertension with target organ damage group was significantly lower than the normal control group in amplitude (P<0.05), hypertension not with target organ damage group and the normal control group was no significant difference in amplitude (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no sigmificant difference in the mesor and the amplitude was no significant difference (P>0.05); diastolic blood pressure population mean cosinor analysis showed that three groups'diastolic blood pressure whole circadian rhythm is existed (p<0.05), hypertension with target organ damage group and hypertension not with target organ damage group was significantly higher than the normal control group in mesor(P<0.01), hypertension with target organ damage group were significantly lower than the normal control group in amplitude (P<0.05); hypertension not with target organ damage group and the normal control group was no significant difference (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no significant difference in the mesor and the amplitude (P>0.05); heart rate population mean cosinor analysis showed that three group'heart rate whole circadian rhythm is existed (p<0.05), hypertension with target organ damage group, hypertension not with target organ damage group was significantly higher than the control group in mesor(P<0.05), hypertension with target organ damage group is significantly lower than normal comtrol group in amplitude (P<0.05), hypertension not with target organ damage group and the normal control group was no significant difference in amplitude (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no significant difference in mesor and amplitede(P>0.05). Conclusions: 1.hypertensions and normal blood pressures,24h systolic blood pressure, diastolic blood pressure, heart rate showed a significant circadian rhythm; 2. compared with normal blood pressures, the characteristics of blood pressure and heart rate circadian rhythm in hypertensions is the systolic blood pressure, diastolic blood pressure, heart rate increased in mesor and systolic blood pressure, heart rate decreased in amplitude; 3. target organ damage in the hypertensions is associated with the circadian rhythm characteristics of blood pressure, heart rate. compared with normal blood pressures, hypertensions with target organ damage systolic blood pressure whole circadian rhythm is not exsisted, systolic blood pressure, diastolic blood pressure, heart rate increased in mesor and decreased in amplitudes; 4. to find out the characteristics of blood pressure and heart rate circadian rhythm is useful for diagnosis of prognosis and chronotherapy to the hypertensions.
结论：1.高血压患者与正常血压患者24h收缩压、舒张压、心率变化均呈明显的近日节律。2.与正常血压者比较,未服用降压药物或停用降压药物的早期轻、中高血压患者血压、心率近日节律特点表现为收缩压、舒张压、心率调整中值升高,收缩压、心率振幅下降。3.高血压患者靶器官损害的发生、发展与血压、心率近日节律改变的发生明显相关,与正常血压者比较,合并靶器官损害的高血压患者血压、心率近日节律特点表现为收缩压整体近日节律消失,收缩压、舒张压、心率的调整中值升高和振幅下降；4.了解高血压患者近日节律特点可以为高血压患者判断预后以及高血压的时间治疗学提供一定参考价值。
Objective:By analyze the circadian rhythm characteristics of blood pressure in hypertensions, discuss the relations between hypertension and the circadian rhythm characteristics of blood pressure. By analyze the circadian rhythm characteristics of blood pressure in hypertensions with tatget organ damage, discuss the relations between the occur and development of target organ damage and blood pressure circadian rhythm characteristics. Provide some valuable reference for hypertension in prognosis s diagnosis and chronotherapy. Methods:This research has collected 24h ambulatory blood pressure data and general clinical information data (including height, weight, past medical history, smoking history, biochemical tests, echocardiography examination, carotid ultrasonography examination,24h urine protein examination, ECG) of 109 cases who were early hypertions degreed 1 or 2 in Department of Cardiology and Department of Physical examination, the second People Hospital of Yibin, First of all, using Single cosinor created by Halberg, the founder of Chronobiology, to study the data of each 24h ambulatory blood pressure, heart rate. Then according to the hypertension'diagnostic criteria in hypertension guidance in China in 2005 and the hypertension'diagnostic criteria of 24h ambulatory blood pressure (ABPM) in hypertension guidance in China in 1999, all subjects were divided into hypertensive (HP) 72 cases and normal control (NM) 37 cases. Using the Population mean cosinor created by Halberg, the founder of Chronobiology, to study the data of 24h ambulatory blood pressure, heart rate of hypertension group and normal control group. Finally, according to the diagnostic criteria of target organ damage, hypertension group was divided into the hypertension with target organ damage group (HPTD) 42 cases and hypertension not with target organ damage group (HPN) 30 cases. Using the Population mean cosinor created by Halberg, the founder of Chronobiology, to study the data of 24h ambulatory blood pressure, heart rate of hypertension with target organ damage group and hypertension not with target organ damage and normal control group. Results:1. Minnesota single cosine analysis:all subjects 24-hour systolic blood pressure, diastolic blood pressure, heart rate showed a significant circadian rhythm (P<0.05).2. the results of hypertensive groups and normal control group'population mean cosinor analysis:sistolic blood pressure population mean cosinor analysis showed that the hypertension group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.05), hypertension was significantly higher than the control group in mesor (P<0.01), the amplitude was significantly lower than the control group (P<0.05); diastolic blood pressure population mean cosinor analysis showed that the hypertension group and normal control group' systolic blood pressure whole circadian rhythm is existed (P<0.01), hypertension group was significantly higher than the normal control group in mesor (P<0.01), the amplitude is no significant difference than the normal control group (P>0.05); heart rate population mean cosinor analysis showed that the hypertension group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.01), hypertension group was significantly higher than the normal control group in mesor (P<0.05), the amplitude was significantly lower than the control group (P<0.05).3. the results of hypertensive with target organ damage groups and hypertension not with target organ damage groups and normal control group'population mean cosinor analysis:sistolic blood pressure population mean cosinor analysis showed that the hypertension with target organ group'systolic blood pressure whole circadian rhythm is not existed (p>0.05), hypertension not with target organ damage group and normal control group'systolic blood pressure whole circadian rhythm is existed (P<0.05); hypertension with target organ damage group and hypertension not with target organ damage group was significantly higher the normal control group in mesor (P<0.01), hypertension with target organ damage group was significantly lower than the normal control group in amplitude (P<0.05), hypertension not with target organ damage group and the normal control group was no significant difference in amplitude (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no sigmificant difference in the mesor and the amplitude was no significant difference (P>0.05); diastolic blood pressure population mean cosinor analysis showed that three groups'diastolic blood pressure whole circadian rhythm is existed (p<0.05), hypertension with target organ damage group and hypertension not with target organ damage group was significantly higher than the normal control group in mesor(P<0.01), hypertension with target organ damage group were significantly lower than the normal control group in amplitude (P<0.05); hypertension not with target organ damage group and the normal control group was no significant difference (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no significant difference in the mesor and the amplitude (P>0.05); heart rate population mean cosinor analysis showed that three group'heart rate whole circadian rhythm is existed (p<0.05), hypertension with target organ damage group, hypertension not with target organ damage group was significantly higher than the control group in mesor(P<0.05), hypertension with target organ damage group is significantly lower than normal comtrol group in amplitude (P<0.05), hypertension not with target organ damage group and the normal control group was no significant difference in amplitude (P>0.05), hypertension with target organ damage group and hypertension not with target organ damage group was no significant difference in mesor and amplitede(P>0.05). Conclusions: 1.hypertensions and normal blood pressures,24h systolic blood pressure, diastolic blood pressure, heart rate showed a significant circadian rhythm; 2. compared with normal blood pressures, the characteristics of blood pressure and heart rate circadian rhythm in hypertensions is the systolic blood pressure, diastolic blood pressure, heart rate increased in mesor and systolic blood pressure, heart rate decreased in amplitude; 3. target organ damage in the hypertensions is associated with the circadian rhythm characteristics of blood pressure, heart rate. compared with normal blood pressures, hypertensions with target organ damage systolic blood pressure whole circadian rhythm is not exsisted, systolic blood pressure, diastolic blood pressure, heart rate increased in mesor and decreased in amplitudes; 4. to find out the characteristics of blood pressure and heart rate circadian rhythm is useful for diagnosis of prognosis and chronotherapy to the hypertensions.
引文
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45.蒋晓云.高血压患者动态血压监测价值探讨[J].现代中西医结合杂志,2003,12(20)：2171-2172.
46.吴洪霞.动态血压监测与靶器官损害[J].实用临床医学,2002,3(6)：65-66.
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21.T. Ohkubo, A. Hozawa, J. Yamaguchi, et al.Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure:the Ohasama study, J. Hypertens.20 (2002) 2183-2189.
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43. T. Ohkubo, A. Hozawa, J. Yamaguchi, et al.Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure:the Ohasama study, J. Hypertens.20 (2002) 2183-2189.
44.夏梦宁,司芩,张文杰.动态血压监测对防治靶器官损害应用价值的研究[J].中国热带医学.2009,9(12)：2260-62.
45.蒋晓云.高血压患者动态血压监测价值探讨[J].现代中西医结合杂志,2003,12(20)：2171-2172.
46.吴洪霞.动态血压监测与靶器官损害[J].实用临床医学,2002,3(6)：65-66.
1.河野雄平.高血压与生物节律[J].日是本医学介绍,2000,21(2)：50.
2. Ramon C. Hermida a, Diana E, et al. Circadian variation of blood pressure: The basis for the chronotherapy of hypertension. Advanced Drug Delivery Reviews,2007,59,904-922.
3. T.G. Pickering, J.E. Hall, L.J. Appel,et al. Recommendations for blood pressure measurement in humans and experimental animals:part 1:blood pressure measurement in humans:a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research, Circulation 111 (2005)697-716.
4. A.M. Birkenhager, A.H. van den Meiracker. Causes and consequences of a non-dipping blood pressure profile.The netherland journal of medicine, 2007,65(4):127-131.
5. Cuspidi C,Meami S,Salerno M,et al. Reproducibility of nocturnal blood pressure fall in early phases of untreated essential hypertension:a prospective observational study. J Hum Hypertens,2004 Jul;18(7):503-9.
6. O'Shea JC, Murphy MB. Nocturnal blood pressure dipping:a consequence of diurnal physical activity blipping?.
7. Am J Hypertens,2000,13:601-6. Takakuwa H, Ise T, Kato T, et al. Diurnal variation of hemodynamic indices in non-dipper hypertensive patients. Hypertens Res,2001,24:195-201.
8. Watanabe Y, Nishimura H, Sanaka S, Otsuka K, Ohkawa S. Does sodium sensitivity affect nocturnal blood pressure variation in outpatients with hypertension? Clin Exp Hypertens 2002;24:99-107.
9. Kanbay M, Turgut F,Uyar ME,et al. Causes and mechanisms of nondipping hypertension.Clin Exp hypertens,2008,Oct,30(7):585-597.
10.Routled F,McFetridge-Durdle. Nondipping blood pressure patterns among individuals with essential hypertension:a review of the literature. Eur J Cardiovasc Nurs,2007 Mar;6(1):9-26.
11.Hermida RC, Chayan L,Ayala DE,et al. Association of metabolic syndrome and blood pressure nondipping profile in untreated hypertension.Am J Hypertens,2009 Mar;22(3):307-13.
12.K. Shimada, K. Kario. Altered circadian rhythm of blood pressure and cerebrovascular damage, Blood Press, Monit,1997,2:333-338.
13.M.B. Davidson, J.K. Hix, D.G. Vidt, D.J. Brotman, Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate, Arch. Intern. Med.166 (2006) 846-852.
14.Turfaner N,Karter Y,Curqunlu A, et al. Blunted nocturnal fall of blood pressure in isolated clinical hypertension. Swiss Med Wkly,2009 May 2, 139(17-18):251-255.
15.Soylu A,Duxenli MA,Yaxici M, et al. The effect of nondipping blood pressure patterns on cardiac structural changes and left ventricular diastolic functions in normotensives. Echocardiography,2009, Apr;26(4):378-387.
16.J.A. Staessen, et al., for the Systolic Hypertension in Europe Trial Investigators, Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension, JAMA,1999,282:539-546.
17.Ersoylu ZD,Tuqcu A, Yildirimturd O,et al. Comparison of the incidences of left ventricular hypertrophy, left ventricular diastolic dysfunction, and arrhythmia between patients with dipper and non-dipper hypertension. Turk Kardiyol Dern Ars,2008 Jul; 36(5):310-317
18.Pierdomenico SD,Lapenna D,Cuccurullo F. Risk of atrial fibrillation in dipper and nondipper sustained hypertensive patients. Blood Press Monit,2008 Aug;13(4):193-197.
19.Rekhviashvili A, Tsinamdzgvrishvili B,Chkhetia M,et al. Relationship of 24-hour blood pressure rhythm with endothelial function and blood rheology. Georgian Med News,2008 Jun;(159):21-26.
20.K. Kario, T.G. Pickering, T. Matsuo, et al.Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives, Hypertension 38 (2001)852-857.
21.T. Ohkubo, A. Hozawa, J. Yamaguchi, et al.Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure:the Ohasama study, J. Hypertens.20 (2002) 2183-2189.
22.关俊文,刘衍宇,江舟,等.高血压病近日节律变化特征的研究.西部医学,2008,5,20(3)：480-484.
23.de la Sierra A,Redon J,Baneqas JR,et al. Prevalence and factors associated with circadian blood pressure patterns in hypertensive patients. Hypertension,2009 Mar;53(3):466-472.
24.Qiu YG,Yao XY,Tao QM,et al. Profile on circadian blood pressure and the influencing factors in essential hypertensive patients after treatment. Zhonghua liu xing Bing Xue Za Zhi,2004 Aug;25(8):710-714.
25.R.C. Hermida, D.E. Ayala, C. Calvo, Administration-time-dependent effects of antihypertensive treatment on the circadian pattern of blood pressure, Curr. Opin. Nephrol. Hypertens.2005,14:453-459.