摘要
第一部分血管超负荷指数和原发性高血压合并代谢综合征患者靶器官损害相关性研究
目的:
观察新诊断的未治疗的高血压病患者合并代谢综合征组(MS+)与非合并代谢综合征组(MS-)的血管超负荷指数(VOI)及临床靶器官的损害情况,进一步研究血管超负荷指数是否和高血压合并代谢综合征的患者的靶器官损害相关。
方法:
研究对象为2006年3月至2008年1月份我院就诊的新诊断的高血压患者187例,其中合并代谢综合征组(MS+,n=79例)和非合并组(MS-,n=108例)。所有患者进行血压测量和心电图检查,计算出血管超负荷指数(VOI),测定血和尿生化指标,检查发现存在的靶器官损害指标,包括左室重量指数(LVMI)、颈动脉中层内膜厚度(CITM)、尿微量白蛋白(MUA)。
结果:
1.合并(MS+)组和非合并组(MS-)相比,年龄、性别、SBP、DBP无显著性差异。FBG、HDL-C、BMI、TG、VOI在两组间比较差异有统计学意义(P<0.01)。
2.MS(+)和MS(-)两组比较:LVH(53.24±10.4 vs 44.2±11.9,P<0.001);CIMT(0.71±0.15 vs 0.65±0.15,P<0.001);LogACR(0.31±0.07 vs 0.06±0.04,P<0.001)差异有统计学意义。MS+组同时伴随着较高的VOI值(64.03±2.15vs 48.23±1.58,P<0)。
3.单变量相关分析发现,VOI和年龄(r=0.147;P≤0.033),SBP(r=0.154;P≤0.0181)、BMI(r=0.220;P≤0.0029)、TG(r=0.175;P≤0.089)正相关。而且和早期靶器官损害LVMI(r=0.125;P≤0.0360)、LogACR(r=0.257;P≤0.0012)、CIMT(r=0.199;P≤0.0142)正相关.
4.多元线性回归分析发现,在调整了年龄、性别、吸烟及血糖的影响外,LVH、CIMT、MUA和VOI有独立的相关性(P<0.001)。
结论:
1.和非合并代谢综合征的高血压组相比,合并代谢综合征组的VOI值明显升高,提示血流循环的负荷增加。
2.高血压合并代谢综合征患者,在检测到心脏损害的同时,伴随着尿微量白蛋白和颈动脉中层内膜增厚、斑块增多,大部分患者可以发现至少一种靶器官损害。临床上对合并代谢综合征的高血压患者应进行亚临床疾病的早期检测和预防。
3.血管超负荷指数和原发性高血压患者的靶器官损害相关,试验证实了VOI可以作为代谢综合征患者的心血管疾病危险因子,血管超负荷指数增加,心血管不利事件发生也增加。
第二部分静息心率和原发性高血压合并代谢综合征患者靶器官损害相关性研究
目的:研究静息心率增加是否与高血压合并代谢综合征患者的靶器官损害相关。
方法:入选对象同第一部分,依据静息心率进行分组处理(A组<60;B组60-80;C组≥80)次/分,每组又分为MS+和MS-亚组,其他检查同第一部分。
结果:
1.三组靶器官损害检出率:LVH(32%vs 43%vs 59%,P均<0.01)、CIMT(5%v27%vs 56%,P均≤0.05)和MUA(21%vs 18%vs 19%,P均<0.05)。随着静息心率的增加,靶器官损害的检出率增加,且有显著性差异。
2.MS+和MS-亚组比较,LVH、CIMT、MUA的发生率MS+组比MS-组增高(40%vs 37%,29%vs 15%,29%vs9%,P均≤0.05)。
3.超声心动图检测值LVMI(176.8±52.3 vs 210.9±57:182.2±49.8 vs 217.8±59;200.8±44.1 vs 218.4±52.3);LVH(39.9±9.8 vs 45.1±10.6;47.2±11.9 vs 53.4±13.4:51.4±12.5 vs 55.3±12.8);以及CIMT(0.54±0.08 vs 0.61±0.11:0.70±0.12 vs0.73±0.19;0.85±0.14 vs 0.92±0.17)值随着静息心率的增加而呈上升趋势。尽管ACR的趋势并不明显(2.97±0.35 vs 6.39±1.22;2.42±1.25 vs 5.52±3.10:4.44±1.87 vs 10.30±3.22)。所有亚组靶器官损害指标在合并MS+组的值高于MS-组,有显著性差异(P均≤0.05)。
结论:
1.静息心率增加仍然是高血压合并代谢综合征的患者靶器官损害的很强的预测因子,尽管是传统的心血管危险因子在临床上仍有意义。
2.代谢综合征增加了高血压病患者的静息心率和靶器官损害,同时静息心率增加的患者合并代谢异常的组分增加,表明代谢综合征和静息心率二者对靶器官的损害可能存在协同作用。
Part one:The Relationship of the blood vascular overload index(VOI) with target organ damage(TOD) in the essential hypertensives with metabolic syndrome.
Objective:
The study was aimed to measure the blood vascular overload index(VOI) in hypertensives with MS and without MS,to search for subclinical target organ damage,We sought to evaluate whether VOI was associated with TOD in the essential hypertensives with MS。
Methods:
The study population was recruited from untreated hypertensive individuals who attended the Clinic of our Department during the period of 2006 Mar to 2008 Jan。All patients had undergone BP measurement and ECG,to calculate the blood vascular overload index(VOI),physical examination and routine biochemical analyses of blood and urineo All patients underwent extensive investigations searching for subclinical target organ damage(TOD),Including LVMI、CTIM and MUA。
Result:
1 Compared without MS-,age、gender、SBP、DBP was no significantly different;FBG、HDC-L、BMI、TG、VOI was significantly higher in the MS+ group(P≤0.001)。
2.Hypertensive patients with the metabolic syndrome had a greater LVH(53.2±10.4 vs 44.2±11.9,P<0.001);CIMT(0.71±0.15 vs 0.65±0.15,P<0.001); LogACR(0.31±0.47 vs 0.06±0.54,P<0.001)。and a greater VOI(64.03±2.15 vs 48.23±1.58,P≤0.001).
3.Nivariate regression analysis show that VOI had significantly positive correlations with age(r=0.147;P≤0.033),SBP(r=0.154;P≤0.0181)、BMI(r=0.220;P≤0.0029)、TG(r=0.175;P≤0.089),and had significantly positive correlation with clinic TOD:LVMI(r=0.125;P≤0.0360), LogACR(r=0.257;P≤0.0012);CIMT(r=0.199;P≤0.0142)
4.Multiple linear regression analysis show VOI was found to be independently associated with LVH、IMT(P≤0.002) and MUA(P≤0.01)、after adjusting for age、gender、and FBG。
Conclusions:
1.Hypertensives with the metabolic syndrome had a greater VOI。It confirms that alterations in vascular structure and function as assessed by LVMI、CTIM and MUA were more frequent in patients with MS than in those without MS。
2.The more pronounced cardiac involvement of hypertensives with MS was paralleled by an increased prevalence of microalbuminuria and carotid artery wall thickening or plaques,hypertensives with MS should underwent extensive investigations searching for subclinical organ damage(TOD)。
3.Blood vascular overload index(VOI) is associated with organ damage in primary hypertension.With MS.The study strengthen the role of this index as a marker of risk and help to explain the high cardiovascular mortality reported in patients with high blood vessel overload index。
Part two:The Relationship of resting heart rate(RHR) with target organ damage (TOD) in the essential hypertensives with MS
Objective:
We sought to evaluate whether increasing resting heart rate has a greater impact on target organ damage in the essential hypertensives with MS。
Methods:
The subjects was the same as the former:A total of 187 hypertensive patients underwent ECG to measure resting heart rate,categorized in three groups(group A≤60;group B:60-80;group C:≥80)beat/min,according to resting heart rate。
Result:
1 Prevalence of LVH(32%vs 43%vs 59%,P≤0.01 for all)、CIMT(5%vs 27%vs 56%,P≤0.05 for all) and MUA(21%vs 18%vs 19%,P≤0.05 for all) was significantly different in three groups.
2 Prevalence rates of LVH,carotid plaques,and microalbuminuria were significantly higher in patients with MS than without MS((40%vs 37%,29%vs 15%,29%vs 9%,P<0.05 for all)。
3 Echocardiography values LVMI(176.8±52.3 vs210.9±57;182.2±49.8vs 217.8±59;200.8±44.1 vs 218.4±52.3);LVH(39.9±9.8 vs 45.1±10.6;47.2±11.9 vs 53.4±13.4;51.4±12.5 vs 55.3±12.8);CIMT(0.54±0.08 vs 0.61±0.11;0.70±0.12 vs 0.73±0.19;0.85±0.14 vs 0.92±0.17) showed a progressive increase from the Low-HR group to higher-HR group o Although,without showing an RHR-related increase for the prevalence of ACR(2.97±0.35 vs 6.39±1.22;2.42±1.25 vs 5.52±3.10;4.44+1.87 vs 10.30±3.22)。In all groups values were markedly altered in patients with MS as compared to those without MS,the difference being statistically significant(P<0.05)。
Conclusions
1.In conclusion,Resting heart rate is still strongly predictors of clinical target organ damage in essential hypertension with metabolic syndrome and that it maintains its role regardless of it is classic cardiovascular risk factor。
2.Metabolism syndrome increases resting heart rate and the target organ damage in hypertension patient,simultaneously increasing resting heart rate followed by increased metabolic anomalies,indicated that metabolism syndrome and increasing resting heart rate have possibly the synergism to the target organ damage in hypertension patients。
引文
1.吴兆苏。我国心血管流行病学发展30年回顾。中华心血管病杂志,2003,31:881-884.
2.武阳丰、王增武、高润霖。中国医疗卫生人员高血压防治观念和防治知识调查。中华心血管病杂志,2004,32(3):264-269
3.王薇、赵冬、刘静,等。中国35-64岁人群心血管病危险因素与发病危险预测模型的前瞻性研究。中华心血管病杂志,2003,31:902-908
4.Vakili BA,Okin PM,Devereux RB:Prognostic implications of left ventricular hypertrophy.Am Heart J 2001;141:334-341.
5.Devereux RB,Bella JN,Palmieri V,Oberman A,Kitzman DW,Hopkins PN,Rao DC,Morgan D,Paranicas M,Fishman D,Arnett DK:Left ventricular systolic dysfunction in a biracial sample of hypertensive adults:the Hypertension Genetic Epidemiology Network(HyperGEN) Study.Hypertension 2001;38:417-423.
6.Simone G,Roman MJ,Alderman MH,Galderisi M,de Divitiis O,Devereux RB:Is high pulse pressure a marker ofpreclinical cardiovascular disease?Hypertension 2005;45:575-579
7.Eckel RH,Grundy SM,Zimmet PZ:The metabolic syndrome.Lancet 2005;365:1415-1428.
8.Grundy SM,Brewer HB Jr,Cleeman JI,Smith SC Jr,Lenfant C:Definition of metabolic syndrome:report of the National Heart,Lung and Blood Institute/American Heart Association conference on scientific issues related to definition.Circulation 2004;109:433-438.
9.Polonsky KS,Given BD,Hirsch LJ,Tillil H,Shapiro ET,Beebe C,et al.Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.N Engl J Med 1988;318:1231-9.
10.O'Rahilly S,Turner RC,Matthews DR.Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes.N Engl J Med.1988;318:1225-30.
11.Cerasi E,Luft R.The plasma insulin response to glucose infusion inhealthy subjects and in diabetes mellitus.Acta Endocrinol(Kbh) 1967;55:278-304.
12.World Health Organization.Definition,diagnosis and classification of Diabetes Mellitus and its complication.Report of a WHO Consultation.Part 1:Diagnosis and Classification of Diabetes mellitus.Geneva,Switzerland:World Health Organization;1999.
13.The IDF consensus worldwide definition of metabolic syndrome.Avaliable from:http://www.idf.org.
14.中华医学会糖尿病分会MS研究协作组.中华医学会糖尿病分会关于MS 的议[J].中华糖尿病杂志,2004,12(3):156.
15.Lakka HM,Laaksonen DE,Lakka TA,Niskanen LK,Kumpusalo E,Tuomilehto J,Salonen JT:The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.JAMA 2002;288:2709-2716.
16.Hu G,Oiao O,Tuomilehto J,Balkau B,Borch-Johnsen K,Pyorala K,for the DECODE Study Group:Prevalence of the metabolic syndrome and its relation to all cause and cardiovascular mortality in nondiabetic European men and women.Arch Intern Med 2004;164:1066-107
17.RecasensM,RicartW,Fernandez2Real JM.Obesity and inflammation[J].Re2 vista DeMedicina De La Universidad De Navarra,2004,48(2):49254.
18.Han TS,Williams K,SattarN,et al.Analysis of obesity and hyperinsulinemia in the development of metabolic syndrome:San Antonio Heart Study[J].Obesity
19.Haffner SM.Obesity and the metabolic syndrome:The San Antonio Heart Study
20.Bloomgarden ZT:Obesity,hypertension,and insulin resistance.Diabetes Care 2002;25:2088-2097.
21.Stamler J,Elliott P,Appel L,Chan Q,Buzzard M,Dennis B,Dyer AR, Elmer P, Greenland P, Jones D, Kesteloot H, Kuller L, Labarthe D, Liu K, Moag-Stahlberg A, Nichaman M, Okayama A, Okuda N, Robertson C, Rodriguez B, Stevens M, Ueshima H, Horn LV, Zhou B: Higher blood pressure in middle-aged American adults with less education-role of multiple dietary factors: the INTERMAP study. J Hum Hypertens 2003; 17:655-775.
22. Mahamat A, Richard F, Arveiler D, Bongard V, Yarnell J, Ducimetiere P, Ruidavets JB, Haas B, Bingham A, Evans A, Amouyel P, Dallongeville J: Body mass index, hypertension and 5-year coronary heart disease incidence in middle aged men: the PRIME study.J Hypertens 2003;21:519 -524.
23. Palmiefi V, Wachtell K, Gerdts E, et al. Left ventficular function and hemodynamic features of inappropriate left ventricular hypertrophy in patients with systemic hypertension: the LIFE study[J]. Am Heart J, 2001, 141(2): 784—791.
24. Celentano A, Palmieri V, Arezzi E, et al. Gender differences in left ventricular chamber and midwall systolic function in normotensive and hypertensive adults[J]. J Hypertens, 2003, 21(7): 1415-1423.
25. Wong CY, O Moore-Sullivan T, Leano N, et aL Alterations of left ventricular myocardial characteristics associated with obesity[J]. Circulation, 2004, 110(19): 3081-3087.
26. Kenchaiah S, Evans JC, Levy D, et aL Obesity and the risk ofheart failureI-J]. N Engl J Med, 2002, 347(5): 305—313.
27. Emoto M, Nishizawa Y, Kawagishi T, et al: Stiffness indexes beta of the common carotid and femoral arteries are associated with insulin resistance in NIDDM. Diabetes Care 1998; 21: 1178-1182.
28. Sarafidis PA, Lasaridis AN, Nilsson PM, et al: Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase. J Hypertens 2004; 22:1769-1777.
29. Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities(?) the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996; 334: 374-381.
30. Safar ME: Systolic hypertension in the elderly: arterial wall mechanical properties and the rennin angiotensin aldosterone system. J Hypertens 2005; 23:673-681.
31. Landsberg L: Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986; 61:1081-1090.
32. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z: Hyperinsulinemia. A link between hypertension, obesity and glucose intolerance. J Clin Invest 1985; 75:809-817.
33. Safar ME, Levy BI, Struijker-Boudier H: Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation 2003; 107: 28642869.
34. Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR: Noninsulin dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes-the ARIC Study.Circulation 1995; 91:1432-1443.
35. Scuteri A, Najjar SS, Muller DC, et al: Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness. J Am Coll Cardiol 2004; 43: 1388-1395.
36. Popele NM, Westendorp IC, Bots ML, et al: Variables of the insulin resistance syndrome are associated with reduced arterial distensibility in healthy non-diabetic middle- aged women. Diabetologia 2000; 43: 665672.
37. Dijk RA, Bakker SJ, Scheffer PG, Heine RJ, Stehouwer CD: Associations of metabolic variables with arterial stiffness in type 2 diabetes mellitus: focus on insulin sensitivity and postprandial triglyceridaemia. Eur J Clin Invest 2003; 33:307315.
38. Facchini F, Chen Y-DI, Clinkingbeard C, Jeppesen J, Reaven GM: Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension. Am J Hypertens 1992; 5:694-699.
39. Karalliedde J, Viberti G.; Evidence for renoprotection by blockade of the renin-angiotensin-aldosterone system in hypertension and diabetes.J Hum Hypertens. 2006 Apr; 20(4):239-53. Review.
40. Fonseca VA. Insulin resistance, diabetes, hypertension, and renin-angiotensin system inhibition: reducing risk for cardiovascular disease.J Clin Hypertens (Greenwich). 2006 Oct;8(10):713-20; quiz 721-2. Review
41. Leung PS, de Gasparo M..Involvement of the pancreatic renin-angiotensin system in insulin resistance and the metabolic syndrome. J Cardiometab Syndr. 2006 Summer; 1(3): 197-203. Review.
42. Nosadini R, Tonolo G.The role of the renin angiotensin hormonal system in the metabolic syndrome and type 2 diabetes. Nutr Metab Cardiovasc Dis. 2004 Apr;14(2):88-93. Review.
43. Engeli S.Role of the renin-angiotensin- aldosterone system in the metabolic syndrome.Contrib Nephrol. 2006; 151:122-34. Review.
44. Sibley S.Hypertension, obesity, and the renin-angiotensin system: a tale of tight associations. Minn Med. 2003 Jan;86(1):46-8.
45. Lewis GF,Carpentier A,Adeli K,et al.Sisordered FAT storage and mobilization in pathogensis of insulin resistence and type 2 diabetes [J].Endocr Rev,2002,23;201-229
46. Abbasi F, McLaughlin T, Lamendola C, et al. Insulin regulation of plasma free fatty acid concentration is abnormal in healthy subjects with muscle insulin resistance [J] Metabolism,2000,49;151-154.
47. eynisdottir S ,Angelin B ,Langin D ,et al. Adipose tissue lipoprotein lipase and hormone -sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome [J] . Arterioscler Thromb Vasc Biol,1997,17;2287-2292
48. Byne CD, Wareham NJ, Brown DC, et al. Hypertriglyceridaemia in subjects with normal an abnormal glucose tolerance relative contribution of insulin secretion, insulin resistance and suppression of plasma non-esterified fatty acids [J] . diabetologia, 1994,37;889-896
49. Kwiterovich PO Jr.Clinical relevance of the biochemical,metabolic,and genetic factors that influence low-density lipprotein heterogeneity [J].Atherosclerosis,1998,140;71-79.
50. Friedwald WT, Levy R, Fredrickson DS: Estimations of serum low density lipoprotein cholesterol without use of preparative ultracentrifuge. Clin Chem 1972; 18:499-502.
51. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N : Echocardiographic assessment of left ventricular hypertrophy. Comparison to necropsy findings. Am J Cardiol 1986; 57: 450-458.
52. Teichholz LE, Kreulen T, Herman MV, Gorlin R: Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence absence of asynergy. Am J Cardiol 1976;37:7-11.
53. Pontremoli R, Sofia A, Ravera M et al. Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications. Hypertension 1997; 30:1135-1143.
54. Hammond IW, Devereux RB, Alderman MH, Lutas EM, Spitzer MC, Crowley JS, Laragh JH: The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension J Am Coll Cardiol 1986; 7:639-650.
55. Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and of their capacity to predict cardiovascular risk. J Am Coll Cardiol. 1995;25:1056 -1062.
56. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 , European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003; 21:1011-1053.
57. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association; National Heart, Lung,and Blood Institute: Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-438.
58. Tomiyama H, Koji Y, Yambe M, et al: Elevated C-reactive protein augments increased arterial stiffness in subjects with metabolic syndrome. Hypertension 2005: 45: 997-1003.
59. Tomiyama H, Hirayama Y, Hashimoto H, et al: The effects of changes in the metabolic syndrome detection status affect on arterial stiffening: a prospective study. Hypertens Res 2006; 29: 673-678.
60. McLeod AL, Uren NG, Wilkinson IB, et al: Non-invasive measures of pulse wave velocity correlate with coronary arterial plaque load in humans. J Hypertens 2004; 22: 363-368.
61. Imanishi R, Seto S, Toda G, et al: High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men. Hypertens Res 2004; 27:71-78.
62. Weber T, Auer J, O'Rourke MF, et al: Arterial stiffness, wave reflections, and the risk of coronary artery disease.Circulation 2004; 109: 184-189.
63. Cockcroft JR, Wilkinson IB, Evans M, et al: Pulse pressure predicts cardiovascular risk in patients with type 2 diabetes mellitus. Am J Hypertens 2005; 18: 1463-1467.
64. Benetos A, Rudnichi A, Safar m, Guize L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension. 1998; 32:560-564.
65. Franklin SS, Khan SA, Wong SA, Larson MG, Levy D. Is pulse pressure useful in predicting coronary heart disease? The Framingham Heart Study. Circulation. 1999; 100:354-360.
66. Chae CU, Pfeffer MA, Glynn RJ, Mitchell GF, Taylor JO, HennekensCH. Increased pulse pressure and risk of heart failure in the elderly. JAMA. 1999; 281:934-639.
67. Stephane Laurent, Pierre Boutouyrie, Roland Asmar, et al. Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients (Hypertension. 2001;37:1236-1241.).
68. Veterans Administration Cooperative Study Groups on Antihypertensive Agents. Effects of treatment on morbidity: results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202:116-22.
69. Veterans Administration Cooperative Study Groups on Antihypertensive Agents. Effects of treatment on morbidity in hypertension: II. Results in patients with diastolic blood pressure averaging 90 through 114mmHg. JAMA 1970; 213: 1143-52.
70. Kannel WB. Blood pressure and-risk of coronary heart disease: the Framineham Study. Dis Chest 1969:56:43-52.
71. Kannel WBY Wolf PA: Verter J, McNa&ra PM. Epidemiologicassessment of the role of blood pressure in stroke: the Framingham Study. JAMA 1970; 214:301-10.
72. Nichols WW, O'Rourke MF. McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed. London, England: Oxford University Press; 1990:77-142,216-269, 283-359,398-37.
73. Safar ME. Pulse pressure in essential hypertension: clinical and therapeutical implications. J Hypertens.1989; 7:769-776.
74. van Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS, Hoeks AP, van der Kuip DA, Hofrnan A, Witteman JC.Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke. 2001; 32:454-460.
75. Blacher J, Safar ME, Guerin AP, Pannier B, Marchais SJ, London GM. Aortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int. 2003; 63:1852-1860.
76. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L,Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension.2001; 37:1236-1241.
77. Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation.2002; 106:2085-2090.
78. Schillaci G, Pirro M, Pucci G, Mannarino MR, Gemelli F, Siepi D,Vaudo G, Mannarino E: Different impact of the metabolic syndrome on left ventricular structure and function in hypertensive men and women. Hypertension 2006; 47:881-886.
79. Sutton-Tyrrell K, Newman A, Simonsick EM, et al. Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition. Hypertension 2001; 38:429-33.
80. Lim JY, Prk SJ, Hwang HY, Park EJ, Nam JH, Kim J, Park SI:TGF-betal induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation. J Mol Cell Cardiol 2005; 39:627-636.
81. Devereux RB, Alderman MH. Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events. Circulation. 1993; 88:1444-1455.
82. FranklinSS, Weber MA.Measuring hypertensive cardiovascular risk: the vascular overload concept [J].Am Heart J.1994 Oct; 128(4):793-803.
83. Smith WM. Treatment of mild hypertension: results of a ten-year intervention trial.Circ Res1977;40(suppl I):198-205
84.Medical Research Council Working Party.MRC trial of treatment of mild hypertension:principal results.Br MED J 1985;291:97-104.
85.Helgeland A.Treatment of mild hypertension:a five year controlled drug trail the OSLO study.Am J Med 1980;69:725-732
86.Management Committee:The Australian Therapeutic Trial in Mild Hypertension.Lancet 1980;1:1261-1267
87.SHEP Cooperative Research Group.Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.JAMA 1991;265:3255-64.
88.Kuramoto K,Matsushita S,Kuwajima I,Murakami M,prospective study on the treatment od mild hypertension in the aged.Jpn heart J.1981;22:75-85
89.Amery A,Brixko P,Clement D,De Schaepdryver A,Fagard R,Forte J,Henry JF,Leonetti G,O'Malley K,Strasser T,Birkenhager W,Bulpitt C,Deruyttere M,Dollery C,Forette F,Hamdy R,Joossens JV,Lund Johansen PL,Petrie J,Tuomilehto J,Williams B.Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial.Lancet 1985;1:1349-1354.
90.Dahlof B,Lindholm LH,Hansson L,Schersten B,Ekbom T,Wester PO.Morbidity and mortality in the Swedish trial in old patients with hypertension (STOP-Hypertension).Lancet 1991;338:1281-1285.
91.王小欣,吕建。高血压病左室质量指数与血管负荷过重指数的关系。中国学影像学杂志,1997,5;226-227
92.文丹 杨琼。中老年高血压患者血管超负荷指数、脉压与左室重量指数相关性的比较[J].高血压杂志,2006,14(3):189-192.
93.吕键 张艳蕾。血管负荷过重指数对高血压病合并脑出血患者的急诊监测,中国综合临床,2001,17(4):253
94.Morcet JF,Safar M,Thomas F,Guize L,Benetos A:Associations between heart rate and other risk factors in a large French population.J Hypertens 1999;17:1671-1676.
95.Ferrieres J,Ruidavets JB:Association between resting heart rate and hypertension treatment in a general population.Am J Hypertens 1999;12:628-631.
96.李玉冰,杨健威,莫丽丽,等.静息心率与冠心病的临床探讨[J].中国心脏起搏与心电生理杂志,2004,18(5):3662368.
97.魏玲,杨丽霞,齐峰,等.冠心病静息心率的变化及其临床意义研究[J].中国心起博与心电生理杂志,2002,16(6):444-446
98.Kristal-Boneh E,Silber H,Harari G,Froom P.The association of resting heart rate with cardiovascular,cancer and all-cause mortality:Eight year follow-up of 3527 male Israeli employees(the CORDIS Study) Eur Heart J 2000;21:116-124.
99.王亚蓉,张丕德,韦建瑞,等,原发性高血压患者静息心率与血脂及靶器官损害的相关性研究[J].广东药学院学报,2006;22(3);328-330
100.Okamura T,HayakawaT,Kadowaki T,Kita Y,Okayama A,Elliott P,et al;NIPPONDATA80 Research Group.Resting heart rate and cause-specific death in a 16.5-year cohort study of the Japanese general population.Am Heart J 2004;147:1024-1032.
101.Fujiura Y,Adachi H,Tsuruta M,Jacobs DR Jr,Hirai Y,Imaizumi T.Heart rate and mortality in a Japanese general population:An 18-year follow-up study.J Clin Epidemiol 2001;54:495-500.
102.Benetos A,Rudnichi A,Thomas F,Safar M,Guize L.Influence of heart rate on mortality in a French population:Role of age,gender,and blood pressure.Hypertensi on 1999;33:44-52.
103.Diaz A,Bourassa MG,Guertin MC,Tardif JC:Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease.Eur HeartJ 2005;26:967-974.
104.Palatini P:Elevated heart rate as a predictor of increased cardiovascular morbidity.J Hypertens 1999;17(Suppl 3):S3-S10
105.FerrieresJ,Ruidavets JB:Association between resting heart rate and hypertension treatment in a general population.Am J Hypertens1999;12:628-631)。
106.Julius S,Palatini P,Nesbitt SD.Tachycardia,an important terminant of coronary risk in hypertension[J].J Hypertens,1998,16:S9-15.
107.Tochikubo O,Mizushima S,WatanabeJ,et al.Base heart rate during sleep in hypertensive and normotensive subjects[J].Hypertens,2001,19:1131-1137.