常染色体显性多囊肾病动脉功能研究
摘要
常染色体显性多囊肾病(autosomal dominant polycystic kidney disease, ADPKD)是人类最常见、危害最大的单基因遗传病之一,在世界范围的发病率为1/400~1/1000,我国目前约有150多万人罹患此病,其中50%患者在60岁时会进展至终末期肾衰竭。但是目前对于该病发病机制及病理生理尚不明了,从而导致治疗方面也无重大突破。因此ADPKD及其并发症的发生、发展仍然是今后工作的重点。
心血管并发症是ADPKD最早发生、最常见的并发症之一,也是其主要死因之一。囊肿扩张和局部肾缺血导致的肾素-血管紧张素-醛固酮系统(RAAS)激活对ADPKD患者动脉粥样硬化、高血压等心血管病发生及肾衰竭进展起重要作用。RAAS在靶器官损害如动脉粥样硬化、左室肥厚、心力衰竭及肾衰竭中起一定作用。RAAS激活开始于疾病早期阶段,故在主要临床表现出现之前即可发生血管损害,如能早期发现、早期干预,则有利于延缓其心血管并发症的进程。
流行病学和临床研究显示动脉损伤是心血管疾病发病和死亡的重要影响因素,其主要的改变包括内皮功能不良、内中膜厚度(IMT)增加及僵硬度增加等。
本研究的目的主要在于观察ADPKD动物模型和患者动脉血管病变,为早期评价ADPKD心血管病危险因素提供依据。
本研究由两部分组成:
1.观察ADPKD模型Han:SPRD大鼠不同表现型不同周龄的血管内皮损伤病理改变,选取4、8、12周龄雄性及雌性SPRD杂合子(Cy/+)和正常(+/+)大鼠各5只,共45只作为研究对象,取降主动脉进行苏木精-伊红染色观察病理形态学变化;免疫组化染色观察细胞间黏附分子-1(ICAM-1)的表达分布。处死动物前测定血压和肾功能。结果发现,光镜下,4周龄大鼠各组均未见明显改变,但8周龄和12周龄雄性Han:SPRD大鼠出现明显的内皮损伤表现,如内皮肿胀、鞋钉样及内皮细胞脱落等,并且12周龄大鼠表现更重。进一步行免疫组织化学检测显示,各周龄雄性SPRD杂合子大鼠内皮细胞表达ICAM-1均增加,由于ICAM-1是内皮细胞损伤的早期标志,故提示内皮细胞功能受损。并且内皮损伤程度与病变严重程度有一定关联,随着血管内皮功能损伤的逐渐加重,雄性SPRD杂合子大鼠肾功能损伤和高血压逐步进展,而病变程度较轻的雌性SPRD杂合子大鼠内皮损伤不明显。不仅如此,早期4周龄的雄性SPRD杂合子大鼠在肾功能尚未出现明显异常及血压尚未显著升高及光镜下未见到显著形态学改变时,即已存在血管内皮功能异常,主动脉内皮细胞ICAM-1表达强度和范围明显增加,显著高于同周龄的雌性SPRD杂合子大鼠和正常大鼠。
2.应用高频超声分别探测ADPKD高血压、ADPKD正常血压、原发性高血压及正常对照4组人群的肱动脉内皮依赖性舒张功能、颈动脉内中膜厚度(IMT)及颈动脉扩张性。结果发现①反应性充血后肱动脉内径变化ADPKD高血压组显著小于原发性高血压组和ADPKD正常血压组,并且ADPKD正常血压组显著小于正常对照;②ADPKD高血压组和原发性高血压组IMT均显著高于ADPKD正常血压组和正常对照;并且ADPKD正常血压组IMT也显著高于正常对照;③横断面扩张性(CD)和弹性模量增值(Einc)ADPKD高血压组和原发性高血压组与ADPKD正常血压组和正常对照有显著差异,并且ADPKD正常血压组与正常对照也有显著差异。
以上研究结果表明:
Han:SPRD大鼠存在内皮功能损伤,该病变可能在ADPKD早期肾功能及血压正常时即已发生。肾功能正常的ADPKD高血压和正常血压患者存在显著的内皮功能受损、IMT增加和颈动脉扩张性降低,提示疾病早期即可能发生动脉损伤。因此,在疾病早期,监测动脉血管功能、采取有效措施延缓动脉损伤的发生、控制其进展对于有效预防ADPKD心血管疾病具有十分重要的意义。
Autosomal dominant polycystic kidney disease(ADPKD) is one of the most common human hereditary kidney diseases with a prevalence of 1/400-1/1000, estimated to affect more than 1.5 million people and account for about 5% of end stage renal disease patients requiring renal replacement therapy in China. The disease is characterized by the progressive formation of multiple renal cysts affecting all segments of the renal tubules and about 50% patients develop renal insufficiency in the fifth and sixth decades of life. However, at present the unclearness of pathogenesis and pathophysiology of ADPKD results in no effective treatment to this disease. Therefore, the development of ADPKD and its complications remains the focus.
Cardiovascular diseases are one of the earlier and more common complications of ADPKD, and also one of its main causes of death. Renin-angiotensin-aldosterone system (RAAS) plays a role in target organ injuries such as atherosclerosis, left ventricular hypertrophy, heart failure and renal failure. RAAS activation starts at early stage of ADPKD, so arteries injury may occur before clinical menifestation appearance. Early diagnosis and intervention may be benefit to postpone the development of cardiovascular complications.
The purpose of our research is observing the arterial changes in animal model and patients of ADPKD, in order to offerring evidence to assess the risk factor of cardiovascular disease in ADPKD.
This study consists of 2 sections:
1. We observed the pathology of thoracic aorta in Han:SPRD rat with difference phenotype and age. The subject included 45 male heterozygous, female heterozygous (Cy / +) and normal (+ / +) SPRD rats ( 4, 8, 12 weeks old). The blood pressure and renal function were measured, and then the rats were killed , descending aorta was obmined to observe the pathomorphological changes with haematine-eosin staining , and the distribution of the expression of intercellular adhesion molecule-1(ICAM-1) was observed with immunohistochemical staining.It was found that there were distinct changes in male heterozygous rats of 8 and 12 weeks old under light microscope, and the expression of ICAM-1 increased in endothelial cell of male heterozygous rats. The extent of damage in endothelium related to severity of disease. With the aggravation of endothelium injury, the renal function damage and hypertension gradually developed. whereas the endothelial injury in female rats whose diseases were not serious. Moreover, the expression of ICAM-1 in 4-week-old male rats increased significantly when its renal function and blood pressure still remained normal.
2. We observed the morphologic, mechanical and functional sonographic parameters of arteties in ADPKD patients with normal renal function. Thirty-two hypertensive and 28 normotensive patients with ADPKD with preserved renal function, 25 patients with essential hypertension, and 30 healthy subjects were included in the study. By means of high-resolution vascular ultrasound, brachial artery endothelial dependent vasodilation (EDV), carotid intima-media thickness (IMT) and distensibility were measured. It is founded that EDV was significant worse in hypertensive patients with ADPKD compared with patients with essential hypertension and normotensive patients with ADPKD, and even in normotensive patients with ADPKD compared with healthy subjects. Carotid IMT was significant greater in both hypertensive and normotensive patients with ADPKD compared with healthy subjects. Moreover, carotid cross-sectional distensibility (CD) and incremental elastic modulus (Einc) differed significantly between both hypertensive and normotensive patients with ADPKD and healthy subjects.
It proved that The endothelium injury of Han:SPRD rat might occurred when renal function and blood pressure were nomal. Both hypertensive and normotensive patients with ADPKD show significant endothelial dysfunction, increased IMT and decreased distensibility, which are predictors of artery injury The endothelium injury might occurred when renal function and blood pressure were nomal. Therefore, it is important for prevention cardiovascular disease in ADPKD to monitor arterial function and control it development and advancement.
心血管并发症是ADPKD最早发生、最常见的并发症之一,也是其主要死因之一。囊肿扩张和局部肾缺血导致的肾素-血管紧张素-醛固酮系统(RAAS)激活对ADPKD患者动脉粥样硬化、高血压等心血管病发生及肾衰竭进展起重要作用。RAAS在靶器官损害如动脉粥样硬化、左室肥厚、心力衰竭及肾衰竭中起一定作用。RAAS激活开始于疾病早期阶段,故在主要临床表现出现之前即可发生血管损害,如能早期发现、早期干预,则有利于延缓其心血管并发症的进程。
流行病学和临床研究显示动脉损伤是心血管疾病发病和死亡的重要影响因素,其主要的改变包括内皮功能不良、内中膜厚度(IMT)增加及僵硬度增加等。
本研究的目的主要在于观察ADPKD动物模型和患者动脉血管病变,为早期评价ADPKD心血管病危险因素提供依据。
本研究由两部分组成:
1.观察ADPKD模型Han:SPRD大鼠不同表现型不同周龄的血管内皮损伤病理改变,选取4、8、12周龄雄性及雌性SPRD杂合子(Cy/+)和正常(+/+)大鼠各5只,共45只作为研究对象,取降主动脉进行苏木精-伊红染色观察病理形态学变化;免疫组化染色观察细胞间黏附分子-1(ICAM-1)的表达分布。处死动物前测定血压和肾功能。结果发现,光镜下,4周龄大鼠各组均未见明显改变,但8周龄和12周龄雄性Han:SPRD大鼠出现明显的内皮损伤表现,如内皮肿胀、鞋钉样及内皮细胞脱落等,并且12周龄大鼠表现更重。进一步行免疫组织化学检测显示,各周龄雄性SPRD杂合子大鼠内皮细胞表达ICAM-1均增加,由于ICAM-1是内皮细胞损伤的早期标志,故提示内皮细胞功能受损。并且内皮损伤程度与病变严重程度有一定关联,随着血管内皮功能损伤的逐渐加重,雄性SPRD杂合子大鼠肾功能损伤和高血压逐步进展,而病变程度较轻的雌性SPRD杂合子大鼠内皮损伤不明显。不仅如此,早期4周龄的雄性SPRD杂合子大鼠在肾功能尚未出现明显异常及血压尚未显著升高及光镜下未见到显著形态学改变时,即已存在血管内皮功能异常,主动脉内皮细胞ICAM-1表达强度和范围明显增加,显著高于同周龄的雌性SPRD杂合子大鼠和正常大鼠。
2.应用高频超声分别探测ADPKD高血压、ADPKD正常血压、原发性高血压及正常对照4组人群的肱动脉内皮依赖性舒张功能、颈动脉内中膜厚度(IMT)及颈动脉扩张性。结果发现①反应性充血后肱动脉内径变化ADPKD高血压组显著小于原发性高血压组和ADPKD正常血压组,并且ADPKD正常血压组显著小于正常对照;②ADPKD高血压组和原发性高血压组IMT均显著高于ADPKD正常血压组和正常对照;并且ADPKD正常血压组IMT也显著高于正常对照;③横断面扩张性(CD)和弹性模量增值(Einc)ADPKD高血压组和原发性高血压组与ADPKD正常血压组和正常对照有显著差异,并且ADPKD正常血压组与正常对照也有显著差异。
以上研究结果表明:
Han:SPRD大鼠存在内皮功能损伤,该病变可能在ADPKD早期肾功能及血压正常时即已发生。肾功能正常的ADPKD高血压和正常血压患者存在显著的内皮功能受损、IMT增加和颈动脉扩张性降低,提示疾病早期即可能发生动脉损伤。因此,在疾病早期,监测动脉血管功能、采取有效措施延缓动脉损伤的发生、控制其进展对于有效预防ADPKD心血管疾病具有十分重要的意义。
Autosomal dominant polycystic kidney disease(ADPKD) is one of the most common human hereditary kidney diseases with a prevalence of 1/400-1/1000, estimated to affect more than 1.5 million people and account for about 5% of end stage renal disease patients requiring renal replacement therapy in China. The disease is characterized by the progressive formation of multiple renal cysts affecting all segments of the renal tubules and about 50% patients develop renal insufficiency in the fifth and sixth decades of life. However, at present the unclearness of pathogenesis and pathophysiology of ADPKD results in no effective treatment to this disease. Therefore, the development of ADPKD and its complications remains the focus.
Cardiovascular diseases are one of the earlier and more common complications of ADPKD, and also one of its main causes of death. Renin-angiotensin-aldosterone system (RAAS) plays a role in target organ injuries such as atherosclerosis, left ventricular hypertrophy, heart failure and renal failure. RAAS activation starts at early stage of ADPKD, so arteries injury may occur before clinical menifestation appearance. Early diagnosis and intervention may be benefit to postpone the development of cardiovascular complications.
The purpose of our research is observing the arterial changes in animal model and patients of ADPKD, in order to offerring evidence to assess the risk factor of cardiovascular disease in ADPKD.
This study consists of 2 sections:
1. We observed the pathology of thoracic aorta in Han:SPRD rat with difference phenotype and age. The subject included 45 male heterozygous, female heterozygous (Cy / +) and normal (+ / +) SPRD rats ( 4, 8, 12 weeks old). The blood pressure and renal function were measured, and then the rats were killed , descending aorta was obmined to observe the pathomorphological changes with haematine-eosin staining , and the distribution of the expression of intercellular adhesion molecule-1(ICAM-1) was observed with immunohistochemical staining.It was found that there were distinct changes in male heterozygous rats of 8 and 12 weeks old under light microscope, and the expression of ICAM-1 increased in endothelial cell of male heterozygous rats. The extent of damage in endothelium related to severity of disease. With the aggravation of endothelium injury, the renal function damage and hypertension gradually developed. whereas the endothelial injury in female rats whose diseases were not serious. Moreover, the expression of ICAM-1 in 4-week-old male rats increased significantly when its renal function and blood pressure still remained normal.
2. We observed the morphologic, mechanical and functional sonographic parameters of arteties in ADPKD patients with normal renal function. Thirty-two hypertensive and 28 normotensive patients with ADPKD with preserved renal function, 25 patients with essential hypertension, and 30 healthy subjects were included in the study. By means of high-resolution vascular ultrasound, brachial artery endothelial dependent vasodilation (EDV), carotid intima-media thickness (IMT) and distensibility were measured. It is founded that EDV was significant worse in hypertensive patients with ADPKD compared with patients with essential hypertension and normotensive patients with ADPKD, and even in normotensive patients with ADPKD compared with healthy subjects. Carotid IMT was significant greater in both hypertensive and normotensive patients with ADPKD compared with healthy subjects. Moreover, carotid cross-sectional distensibility (CD) and incremental elastic modulus (Einc) differed significantly between both hypertensive and normotensive patients with ADPKD and healthy subjects.
It proved that The endothelium injury of Han:SPRD rat might occurred when renal function and blood pressure were nomal. Both hypertensive and normotensive patients with ADPKD show significant endothelial dysfunction, increased IMT and decreased distensibility, which are predictors of artery injury The endothelium injury might occurred when renal function and blood pressure were nomal. Therefore, it is important for prevention cardiovascular disease in ADPKD to monitor arterial function and control it development and advancement.
引文
[1] DAI Bing, MEI Chang-lin. Research on autosomal dominant polycystic kidney disease in China. Chinese Medical Journal, 2006, 119(22):1915-1924
[2] Witzgall R. New developments in the field of cystic kidney diseases. Curr Mol Med, 2005, 5(5):455~465
[3] Bogdanova N, Markoff A, Horst J. Autosomal dominant polycystic kidney disease - clinical and genetic aspects. Kidney Blood Press Res, 2002,25(5):265~283
[4] Kennefick T, AN imriM, Oyama T, et al. Hypertension and renal injury in experimental polycystic kidney disease. Kidney Int, 1999, 56(9):2181~2190
[5] Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease.Curt Opin Lipidol, 2001, 12:383~389
[6] Ross R. Athemsclemsis: an inflammatory disease. N E J Med, 1999, 340:115~126
[7] Ray KK, Morrow DA, Shui A, et al. Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22). Am J Cardiol, 2006, 98(7):861~865
[8] Jenny NS, Arnold AM, Kuller LH, et al. Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults. J Thromb Haemost, 2006, 4(1):107~113
[9] Brazil M. Atherosclerosis: Go with the flow. Nat Rev Drug Discov, 2005, 4(11):883
[10] Dessein PH, Joffe BI, Singh S. Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Arthritis Res Ther, 2005, 7(3):R634~R643
[11] Larsson PT, Hallerstam S, Rosfors S, et al. Circulating markers of inflammation are related to carotid artery atherosclerosis. Int Angiol, 2005, 24(1):43~51
[12] Hillis GS, Flapan AD. Cell adhesion molecules in cardiovascular disease: a clinical perspective. Heart, 1998, 79:429~431
[13] Tzoulaki I, Murray GD, Lee AJ, et al. C-reactive protein, interleukin-6, andsoluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation, 2005, 112(7):976~983
[14] Hwang SJ, Ballantyne CM, Sharrett AR, et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities(ARIC)study. Circulation, 1997, 96:4219~4225
[15] Silvestro A, Brevetti G, Schiano V, et al. Adhesion molecules and cardiovascular risk in peripheral arterial disease. Soluble vascular cell adhesion molecule-1 improves risk stratification. Thromb Haemost, 2005, 93(3):559~563
[16] Boyle JJ. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol, 2005, 3(1):63~68
[17] Filippo C, Luigi MB, Antonion B, et al. Role ofinflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol,1997,80:10~16
[18] Davies MJ, Gordon, Gearing AJ,et al. The expression of the adhesion molecule ICAM-1,BCAM-1,PECAM-1 and E-selectin in human atherogenesis.J Patho1, 1993, 171:223~229
[19] Calabresi L, Gomaraschi M, Villa B, et al. Elevated soluble ceHular adhesion molecules in subjects with low HDL-cholesterol.Arterioscler Thromh Vase Binl, 2002, 22:656~661
[20] Matsumoto K, Sera Y, Nakamura H, et al. Serum concentrations of soluble adhesion molecules are related to degree of hyperglycemia and insulin resistance in patients with type 2 diabetes mellitus. Diabets Res Clin Pract, 2002, 55:131~138
[21] Wu KK, Aleksic N, Ballantyne CM, et al. sICAM had a significant increase in the risk of CHD event. Circulation, 2003, 107:I729~1732
[22] Ridker PM, Hennekens CH, Roitman-Johnsion B, et al. Plasma concentration of soluble intercellular adhesion molecule-1 and risks of future myocardial infarction in apparently healthy men. Lancet, 1998, 351:88~92
[23] Luc G, Arveiler D, Evans A, et al. Circulating soluble adhesion moleculesICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study. Atherosclerosis, 2003, 170:169~176
[24] Andrew D, Brann G, Jean A, et al. Circulation endothelial cell/leucocyte adhesion molecules in ischaemic heart disease. Br J Haematology, I996, 95:23~26
[25] Inoue T, Hoshi K, Yaguchi J, et al. Serum levels of circulating adhesion moleeules after coronary angioplasty.Cardiology, 1999, 83:3842
[26] Yamazaki T, Seko Y, Tamatani T, et al. Expression of ICAM-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. Circulation, I994, 85:546~578
[27] Cowley BD Jr, Gudapaty S, Kraybill AL, et al. Autosomal-dominant polycystic kidney disease in the rat. Kidney Int, 1993, 43: 522~534,
[28] Messow C,Heider JJ,Hackbarth H, et al. Morphometric studies of the proximal tubules of the rat kidney considering the effect of the method of killing.Berl Munch Tierarztl Wochenschr. 1992, 105(9):294~299
[29] Zeier M, Pohlmeyer G, Deerberg F,et al. Progression of renal failure in the Han: SPRD polycystic kidney rat. Nephrology Dialysis Transplantation, 1994, 9: 1734~1739
[30] Gile RD, Cowley BD Jr, Gattone VH 2nd, et al. Effect of lovastatin on the development of polycystic kidney disease in the Han:SPRD rat. Am J Kidney Dis, 1995, 26(3):501~507
[31] Schafer K, Gretz N, Bader M, et al. Characterization of the Han:SPRD rat model for hereditary polycystic kidney disease. Kidney Int, 1994, 46(1):134~152
1 梅长林。常染色体显性遗传性多囊肾病研究的热点问题。第二军医大学学报,2003,24(1):1~4
2 Brunner HR. Experimental and clinical evidence that angiotensinⅡis an independent risk factor for cardiovascular disease. Am J Cardiol, 2001, 87:3C~9C
3 Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardial, 2002, 39:257~265
4 O’Leary DH, Polak JF. Intima-media thickness: A tool for atherosclerosis imaging and event prediction. Am J Cardiol, 2002, 90:18L~21L
5 Arnett DK, Boland LL, Evans GW, et al. Hypertension and arterial stiffness: the Atherosclerosis Risk in Communities Study. ARIC Investigators. Am J Hypertens, 2000,13:317~323
6 Sinibaldi D, Malenas S, Mingarelli R, et a1. Prenatal ultrasonographic findings of dominant polycystic kidney disease and postnatal renal evolution. Am J Med Gen,1996,65:237
7 Fick-Brosnahan GM, Belz MM, McFann KK, et al. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis, 2002,39:1127~1134
8 Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheralartery tone in humans. Circulation, 1989, 79(1):93~100
9 Kawasaki M, Takatsu H, Noda T, et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. J Am Coll Cardiol, 2001,38(2):486~492
10 Aggoun Y, Bonnet D, Sidi D et al. Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol, 2000,20:2070~2075
11 Wang D, Iversen J, Wilcox CS, et al. Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease. Kidney Int, 2003, 64:1381~1388
12 Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardial, 2002, 39:257~265
13 Esper RJ, Nordaby RA, Vilarino JO, et al. The Endothelial Dysfunction. Cardiovasc Diabetol, 2006, 23, 5(1):4
14 Widlansky ME, et al. The Clinical implication of endothelial dysfunction. JACC, 2003, 42: 449
15 Ganz P, et al. Testing endothelial vasomotor function: NO, a multipotent molecule. Circulation, 2003,108: 2049
16 Targonsks PV, et al. coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation, 2003, 107:2805
17 Kali A, Janosi A. Endothelial function in high risk cardiovascular patients. Orv Hetil, 2006, 22, 147(3):99~106
18 Kawasaki M, Takatsu H, Noda T et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. J Am Coll Cardiol, 2001,38(2):486~492
19 Muto S, Aiba A, Saito Y, et al. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet 2002; 11:1731~1742
20 Devuyst O, Persu A, Stoenoiu MS, et al. ENOS polymorphism and renal diseaseprogression in autosomal dominant polycystic kidney disease. Am J Kidney Dis, 2003, 41: 1124~1125
21 Simon A, Megnien JL, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia. Circulation, 1997, 96(7):2449~2452
22 Aminbakhsh A, Frohlich J, Mancini GB. Detection of early atherosclerosis with B mode carotid ultrasonography: assessment of a new quantitative approach. Clin Invest Med, 1999,22(6):265~274
23 Sass C, Zannad F, Herbeth B, et al. Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort. Atherosclerosis, 1998, 140(1):89~95
24 Kauma H, Paivansalo M, Savolainen MJ, et al. Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis. J Hypertens, 1996, 14(10):1183~1187
25 Bots ML, Launer LJ, Lindemans J, et al. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study. J Intern Med, 1997, 242(4):339~347
26 Megnien JL, Gariepy J, Saudubray JM, et al. Evidence of carotid artery wall hypertrophy in homozygous homocystinuria. Circulation, 1998,98(21):2276~2281
27 Coles KA, Plant AJ, Riley T et al. Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. Am J Cardiol, 1999, 84(7): 825~828
28 Nieto FJ, Adam E, Sorlie P, et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation, 1996, 94(5):922~927
29 Sorlie PD, Adam E, Melnick SL, et al. Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol, 1994, 42(1):33~37
30 Denarie N, Gariepy J, Chironi G, et al. Distribution of ultrasonographically- assessed dimensions of common carotid arteries in healthy adults of both sexes. Atherosclerosis, 2000,148(2):297~302
31 Demirovic J, Nabulsi A, Folsom AR, et al. Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation, 1993,88(6):2787~2793
32 Lamont D, Parker L, White M, et al. Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study. BMJ, 2000, 320(7230): 273~278
33 Schmidt-Trucksass AS, Grathwohl D, et al. Relation of leisure-time physical activity to structural and functional arterial properties of the common carotid artery in male subjects. Atherosclerosis, 1999,145(1):107~114
34 Bensen JT, Li R, Hutchinson RG, et al. Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities. Genet Epidemiol, 1999, 16(2): 165~178
35 Lindberg G, Rastam L, Lundblad A, et al. The association between serum sialic acid and asymptomatic carotid atherosclerosis is not related to antibodies to herpes type viruses or Chlamydia pneumoniae. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Int J Epidemiol, 1997, 26(6):1386~1391
36 Chen L, Patsch W, Boerwinkle E. HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid phenotypes and carotid artery atherosclerosis. Hum Genet, 1996,98(5):551
37 Saskia JV, Isabel F, Jos WRT, et al. Birthweight and arterial stiffness and blood pressure in adulthood—Results from the Amsterdam Growth and Health Longitudinal Study. Int J Epidem, 2004, 33(1):154~161
38 Stefan S, Annewieke WB, Clemens S, et al. Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation, 2004,110:344~348
39 Hausberg M, Kisters K, Kosch M, et al. Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients. Kidney Int, 1999,55:1104~1110
1 Simon A, Megnien JL, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia. Circulation, 1997,96(7):2449-52
2 Aminbakhsh A, Frohlich J, Mancini GB. Detection of early atherosclerosis with B mode carotid ultrasonography: assessment of a new quantitative approach. Clin Invest Med, 1999,22(6):265-74
3 Greenland P, Abrams J, Aurigemma GP, et al. Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden: Writing Group III. Circulation, 2000 ,101(1):E16-22
4 Agewall S, Wikstrand J, Samuelsson O. The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. Risk Factor Intervention Study Group J Intern Med, 1994 ,236(6):651-9
5 Kanters SD, Algra A, van Leeuwen MS, et al. Reproducibility of in vivo carotid intima-media thickness measurements: a review. Stroke, 1997,28(3):665-71
6 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation, 1986,74(6):1399-406
7 Howard G, Sharrett AR, Heiss G et al. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. Stroke, 1993,24(9):1297-304
8 Gariepy J, Salomon J, Denarie N, et al. Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study. Arterioscler Thromb Vasc Biol, 1998,18(4):584-90
9 Graf S, Gariepy J, Massonneau M et al. Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing. Ultrasound Med Biol, 1999,25(9):1353-63
10 Tang R, Hennig M, Thomasson B et al. Baseline reproducibility of B-mode ultrasonic measurement of carotid arte ry intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA). .J Hypertens, 2000,18(2):197-201
11 Denarie N, Gariepy J, Chironi G. et al. Distribution of ultrasonographically- assessed dimensions of common carotid arteries in healthy adults of both sexes. Atherosclerosis, 2000,148(2):297-302
12 Sharrett AR, Sorlie PD, Chambless Le et al. Relative importance of various risk factors for asymptomatic carotid atherosclerosis versus coronary heart disease incidence: the Atherosclerosis Risk in Communities Study. Am J Epidemiol, 1999,149(9):843-52
13 Mannami T, Baba S, Ogata J. Strong and significant relationships betweenaggregation of major coronary risk factors and the acceleration of carotid atherosclerosis in the general population of a Japanese city: the Suita Study. Arch Intern Med, 2000,160(15):2297-303
14 Zanchetti A, Crepaldi G, Bond MG. Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group. J Hypertens, 2001,19(1):79-88
15 Gariepy J, Simon A, Massonneau M, et al. Wall thickening of carotid and femoral arteries in male subjects with isolated hypercholesterolemia. PCVMETRA Group. Prevention Cardio-Vasculaire en Medecine du Travail. Atherosclerosis, 1995,113(2):141-51
16 Mykkanen L, Zaccaro DJ, O'Leary DH, et al. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke, 1997 ,28(9):1710-6
17 Persson J, Formgren J, Israelsson B, et al. Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb, 1994,14(2):261-4
18 Skoglund-Andersson C, Tang R, Bond MG, et al. LDL particle size distribution is associated with carotid intima-media thickness in healthy 50-year-old men. Arterioscler Thromb Vasc Biol, 1999 ,19(10):2422-30
19 Terry JG, Howard G, Mercuri M et al. Apolipoprotein E polymorphism is associated with segment-specific extracranial carotid artery intima-media thickening. Stroke, 1996,27(10):1755-9
20 Schreiner PJ, Heiss G, Tyroler HA, et al. Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol, 1996,16(3):471-8
21 Fukumoto M, Shoji T, Emoto M, et al. Antibodies against oxidized LDL and carotid artery intima-media thickness in a healthy population. Arterioscler Thromb Vasc Biol, 2000,20(3):703-7
22 Matthews KA, Owens JF, Kuller LH, et al. Are hostility and anxiety associated with carotid atherosclerosis in healthy postmenopausal women? Psychosom Med, 1998,60(5):633-8
23 Diez-Roux AV, Nieto FJ, Tyroler HA, et al. Social inequalities and atherosclerosis. The atherosclerosis risk in communities study. Am J Epidemiol, 1995,141(10):960-72
24 Levenson J, Gariepy J, Del-Pino M, et al. Association of plasma viscosity and carotid thickening in a French working cohort. Am J Hypertens, 2000,13(7):753-8
25 Bots ML, van Swieten JC, Breteler Mm, et al. Cerebral white matter lesions and atherosclerosis in the Rotterdam Study. Lancet, 1993,341(8855):1232-7
26 Crouse JR 3rd, Craven TE, Hagaman AP, et al. Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery. Circulation, 1995,92(5):1141-7
27 Cuspidi C, Lonati L, Sampieri L et al. Left ventricular concentric remodelling and carotid structural changes in essential hypertension.J Hypertens, 1996,14(12):1441-6
28 Mykkanen L, Zaccaro DJ, O'Leary DH, et al. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke, 1997 ,28(9):1710-6
29 Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997 ,96(5):1432-7
30 Hashimoto M, Eto M, Akishita M et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol, 1999 ,19(11):2795-800
31 Shinozaki K, Hattori Y, Suzuki M et al. Insulin resistance as an independent risk factor for carotid artery wall intima media thickening in vasospastic angina. Arterioscler Thromb Vasc Biol, 1997,17(11):3302-10
32 Olsen MH, Fossum E, Hjerkinn E et al. Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS,a LIFE sub study. Insulin Carotids US Scandinavia. J Hypertens, 2000,18(1):75-81
33 Haffner SM, D'Agostino R, Mykkanen L et al. Proinsulin and insulin concentrations in relation to carotid wall thickness: Insulin Resistance Atherosclerosis Study. Stroke, 1998,29(8):1498-503
34 Chen L, Patsch W, Boerwinkle E. HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid phenotypes and carotid artery atherosclerosis. Hum Genet, 1996,98(5):551-6
35 Sass C, Zannad F, Herbeth B, et al. Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort. Atherosclerosis, 1998,140(1):89-95
36 Kauma H, Paivansalo M, Savolainen MJ, et al. Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis. J Hypertens, 1996,14(10):1183-7
37 Bots ML, Launer LJ, Lindemans J, et al. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study. J Intern Med, 1997,242(4):339-47
38 Megnien JL, Gariepy J, Saudubray JM, et al. Evidence of carotid artery wall hypertrophy in homozygous homocystinuria. Circulation, 1998,98(21):2276-81
39 Coles KA, Plant AJ, Riley T, et al. Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. Am J Cardiol, 1999,84(7):825-8
40 Nieto FJ, Adam E, Sorlie P, et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation, 1996,94(5):922-7
41 Sorlie PD, Adam E, Melnick SL, et al. Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol, 1994,42(1):33-7
42 Demirovic J, Nabulsi A, Folsom AR, et al. Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation,1993,88(6):2787-93
43 Lamont D, Parker L, White M, et al. Risk of cardiovascular disease measured by carotid intima-media thic kness at age 49-51: lifecourse study. BMJ, 2000,320(7230):273-8
44 Schmidt-Trucksass AS, Grathwohl D, et al. Relation of leisure-time physical activity to structural and functional arterial properties of the common carotid artery in male subjects. Atherosclerosis, 1999,145(1):107-14
45 Bensen JT, Li R, Hutchinson RG, et al. Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities. Genet Epidemiol, 1999,16(2):165-78
46 Lindberg G, Rastam L, Lundblad A, et al. The association between serum sialic acid and asymptomatic carotid atherosclerosis is not related to antibodies to herpes type viruses or Chlamydia pneumoniae. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Int J Epidemiol, 1997,26(6):1386-91
47 Rohde LE, Lee RT, Rivero J, et al. Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol, 1998,18(11):1765-70
48 Bizbiz L, Bonithon-Kopp C, Ducimetiere P, et al. Relation of serum elastase activity to ultrasonographically assessed carotid artery wall lesions and cardiovascular risk factors. The EVA study. Atherosclerosis, 1996,120(1-2):47-55
49 Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb, 1991,11(5):1245-9
50 Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol, 2000,151(5):478-87
51 O'Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.N Engl J Med, 1999,340(1):14-22
52 Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997,96(5):1432-7
53 Hodis HN, Mack WJ, LaBree L, et al. The role of carotid arterial intima-media thickness in predicting clinical coronary events.Ann Intern Med, 1998,128(4):262-9
54 Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation, 1995,92(7):1758-64
55 Mercuri M, Bond MG, Sirtori CR, et al. Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study. Am J Med, 1996,101(6):627-34
56 Crouse JR 3rd, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II) Am J Cardiol, 1995,75(7):455-9
57 de Groot E, Jukema JW, Montauban van, et al. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).J Am Coll Cardiol, 1998,31(7):1561-7
58 Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.Circulation, 1994,90(4):1679-87
59 Smilde TJ, van Wissen S, Wollersheim H, et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet, 2001,357(9256):577-81
60 Borhani NO, Mercuri M, Borhani PA, et al. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.JAMA, 1996,276(10):785-91
61 Zanchetti A, Rosei EA, Dal Palu C, et al. The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens, 1998,16(11):1667-76
62 Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation, 2000,102(13):1503-10
63 Lonn E, Yusuf S, Dzavik V, et al. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation, 2001,103(7):919-25
64 Blankenhorn DH, Selzer RH, Crawford DW, et al. Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation, 1993,88(1):20-8
65 Hodis HN, Mack WJ, LaBree L, et al. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled clinical trial. Ann Intern Med, 1996,124(6):548-56
66 MacMahon S, Sharpe N, Gamble G, et al. Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group. Circulation, 1998,97(18):1784-90
67 Simon A, Gariepy J, Moyse D, et al. Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes. Circulation, 2001,103(24):2949-54
68 Linhart A, Gariepy J, Giral P, et al. Carotid artery and left ventricular structural relationship in asymptomatic men at risk for cardiovascular disease. Atherosclerosis, 1996,127(1):103-12
69 Cooke JP. The endothelium: a new target for therapy. Vasc Med, 2000;5(1):49-53
70 Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet,1992, 340(8828):1111-5
71 chachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease.Circulation, 2000, 1(16):1899-906
72 O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.Circulation, 1997, 95(5):1126-31
73 Vogel RA. Cholesterol lowering and endothelial function. Am J Med, 1999, 107(5):479-87
74 Mombouli JV, Vanhoutte PM. Endothelial dysfunction: from physiology to therapy.J Mol Cell Cardiol, 1999, 31(1):61-74
75 YangY, Loscalzo J. Regulation of tissue factor expression in human microvascular e ndothelial cells by nitric oxide.Circulation, 2000, 101(18):2144-8
76 Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, 288(5789):373-6
77 ai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress.Circ Res. 2000, 87(10):840-4
78 Pepine CJ. Clinical implications of endothelial dysfunction. Clin Cardiol, 1998, 21(11):795-9
79 Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.Circulation, 2000, 7;101(9):948-54
80 aitakari OT, Celermajer DS. Testing for endothelial dysfunction. Ann Med, 2000, 32(5):293-304
81 Wang J, Brown MA, Tam SH, et al. Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol, 1997, 24(6):418-20
82 Huggins GS, Pasternak RC, Alpert NM, et al. Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. Circulation,1998, 98(13):1291-6
83 Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation, 1989, 79(1):93-100
84 Dimmeler S, Fleming I, Fisslthaler B, et al. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature, 1999,399(6736):601-5
85 Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation. Clin Sci (Lond), 2000, 99(4):261-7
86 Vogel RA. Measurement of endothelial function by brachial artery flow-mediated vasodilation. Am J Cardiol, 2001, 88(2A):31E-34E
87 Gokce N, Holbrook M, Hunter LM, et al. Acute effects of vasoactive drug treatment on brachial artery reactivity. J Am Coll Cardiol, 2002, 40(4):761-5
88 Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol, 1995, 26(5):1235-41
89 Celermajer DS, Sorensen KE, Bull C, et al. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol, 1994, 24(6):1468-74
90 Enderle MD, Schroeder S, Ossen R, Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease. Heart, 1998, 80(4):349-54
91 Kuvin JT, Patel AR, Sliney KA, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol, 2001, 38(7):1843-9
92 Gokce N, Keaney JF Jr, Hunter LM, Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation, 2002, 105(13):1567-72
93 Woodman RJ, Playford DA, Watts GF, et al. Improved analysis of brachial artery ultrasound using a novel edge-detection software system.J Appl Physiol, 2001,91(2):929-37
94 Bressler B, Chan S, Mancini GB. Temporal response of brachial artery dilation after occlusion and nitroglycerin. Am J Cardiol, 2000, 85(3):396-400, A10
95 van der Heijden-Spek JJ, Staessen JA, Fagard RH, et al. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study.Hypertension, 2000, 35(2):637-42
96 Herrington DM, Fan L, Drum M, et al. Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk, 2001, 8(5):319-28
97 Lieberman EH, Gerhard MD, Uehata A, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med, 1994, 121(12):936-41
98 Ringqvist A, Caidahl K, Petersson AS, Wennmalm A. Diurnal variation of flow-mediated vasodilation in healthy premenopausal women.Am J Physiol Heart Circ Physiol, 2000, 279(6):H2720-5
99 Etsuda H, Takase B, Uehata A, Morning attenuation of endothelium-dependent, flow-mediated dilation in healthy young men: possible connection to morning peak of cardiac events? Clin Cardiol, 1999, 22(6):417-21
100 Perregaux D, Chaudhuri A, Rao S. Brachial vascular reactivity in blacks.Hypertension, 2000, 36(5):866-71
[2] Witzgall R. New developments in the field of cystic kidney diseases. Curr Mol Med, 2005, 5(5):455~465
[3] Bogdanova N, Markoff A, Horst J. Autosomal dominant polycystic kidney disease - clinical and genetic aspects. Kidney Blood Press Res, 2002,25(5):265~283
[4] Kennefick T, AN imriM, Oyama T, et al. Hypertension and renal injury in experimental polycystic kidney disease. Kidney Int, 1999, 56(9):2181~2190
[5] Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease.Curt Opin Lipidol, 2001, 12:383~389
[6] Ross R. Athemsclemsis: an inflammatory disease. N E J Med, 1999, 340:115~126
[7] Ray KK, Morrow DA, Shui A, et al. Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22). Am J Cardiol, 2006, 98(7):861~865
[8] Jenny NS, Arnold AM, Kuller LH, et al. Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults. J Thromb Haemost, 2006, 4(1):107~113
[9] Brazil M. Atherosclerosis: Go with the flow. Nat Rev Drug Discov, 2005, 4(11):883
[10] Dessein PH, Joffe BI, Singh S. Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis. Arthritis Res Ther, 2005, 7(3):R634~R643
[11] Larsson PT, Hallerstam S, Rosfors S, et al. Circulating markers of inflammation are related to carotid artery atherosclerosis. Int Angiol, 2005, 24(1):43~51
[12] Hillis GS, Flapan AD. Cell adhesion molecules in cardiovascular disease: a clinical perspective. Heart, 1998, 79:429~431
[13] Tzoulaki I, Murray GD, Lee AJ, et al. C-reactive protein, interleukin-6, andsoluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation, 2005, 112(7):976~983
[14] Hwang SJ, Ballantyne CM, Sharrett AR, et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities(ARIC)study. Circulation, 1997, 96:4219~4225
[15] Silvestro A, Brevetti G, Schiano V, et al. Adhesion molecules and cardiovascular risk in peripheral arterial disease. Soluble vascular cell adhesion molecule-1 improves risk stratification. Thromb Haemost, 2005, 93(3):559~563
[16] Boyle JJ. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol, 2005, 3(1):63~68
[17] Filippo C, Luigi MB, Antonion B, et al. Role ofinflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol,1997,80:10~16
[18] Davies MJ, Gordon, Gearing AJ,et al. The expression of the adhesion molecule ICAM-1,BCAM-1,PECAM-1 and E-selectin in human atherogenesis.J Patho1, 1993, 171:223~229
[19] Calabresi L, Gomaraschi M, Villa B, et al. Elevated soluble ceHular adhesion molecules in subjects with low HDL-cholesterol.Arterioscler Thromh Vase Binl, 2002, 22:656~661
[20] Matsumoto K, Sera Y, Nakamura H, et al. Serum concentrations of soluble adhesion molecules are related to degree of hyperglycemia and insulin resistance in patients with type 2 diabetes mellitus. Diabets Res Clin Pract, 2002, 55:131~138
[21] Wu KK, Aleksic N, Ballantyne CM, et al. sICAM had a significant increase in the risk of CHD event. Circulation, 2003, 107:I729~1732
[22] Ridker PM, Hennekens CH, Roitman-Johnsion B, et al. Plasma concentration of soluble intercellular adhesion molecule-1 and risks of future myocardial infarction in apparently healthy men. Lancet, 1998, 351:88~92
[23] Luc G, Arveiler D, Evans A, et al. Circulating soluble adhesion moleculesICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study. Atherosclerosis, 2003, 170:169~176
[24] Andrew D, Brann G, Jean A, et al. Circulation endothelial cell/leucocyte adhesion molecules in ischaemic heart disease. Br J Haematology, I996, 95:23~26
[25] Inoue T, Hoshi K, Yaguchi J, et al. Serum levels of circulating adhesion moleeules after coronary angioplasty.Cardiology, 1999, 83:3842
[26] Yamazaki T, Seko Y, Tamatani T, et al. Expression of ICAM-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. Circulation, I994, 85:546~578
[27] Cowley BD Jr, Gudapaty S, Kraybill AL, et al. Autosomal-dominant polycystic kidney disease in the rat. Kidney Int, 1993, 43: 522~534,
[28] Messow C,Heider JJ,Hackbarth H, et al. Morphometric studies of the proximal tubules of the rat kidney considering the effect of the method of killing.Berl Munch Tierarztl Wochenschr. 1992, 105(9):294~299
[29] Zeier M, Pohlmeyer G, Deerberg F,et al. Progression of renal failure in the Han: SPRD polycystic kidney rat. Nephrology Dialysis Transplantation, 1994, 9: 1734~1739
[30] Gile RD, Cowley BD Jr, Gattone VH 2nd, et al. Effect of lovastatin on the development of polycystic kidney disease in the Han:SPRD rat. Am J Kidney Dis, 1995, 26(3):501~507
[31] Schafer K, Gretz N, Bader M, et al. Characterization of the Han:SPRD rat model for hereditary polycystic kidney disease. Kidney Int, 1994, 46(1):134~152
1 梅长林。常染色体显性遗传性多囊肾病研究的热点问题。第二军医大学学报,2003,24(1):1~4
2 Brunner HR. Experimental and clinical evidence that angiotensinⅡis an independent risk factor for cardiovascular disease. Am J Cardiol, 2001, 87:3C~9C
3 Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardial, 2002, 39:257~265
4 O’Leary DH, Polak JF. Intima-media thickness: A tool for atherosclerosis imaging and event prediction. Am J Cardiol, 2002, 90:18L~21L
5 Arnett DK, Boland LL, Evans GW, et al. Hypertension and arterial stiffness: the Atherosclerosis Risk in Communities Study. ARIC Investigators. Am J Hypertens, 2000,13:317~323
6 Sinibaldi D, Malenas S, Mingarelli R, et a1. Prenatal ultrasonographic findings of dominant polycystic kidney disease and postnatal renal evolution. Am J Med Gen,1996,65:237
7 Fick-Brosnahan GM, Belz MM, McFann KK, et al. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am J Kidney Dis, 2002,39:1127~1134
8 Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheralartery tone in humans. Circulation, 1989, 79(1):93~100
9 Kawasaki M, Takatsu H, Noda T, et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. J Am Coll Cardiol, 2001,38(2):486~492
10 Aggoun Y, Bonnet D, Sidi D et al. Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol, 2000,20:2070~2075
11 Wang D, Iversen J, Wilcox CS, et al. Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease. Kidney Int, 2003, 64:1381~1388
12 Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardial, 2002, 39:257~265
13 Esper RJ, Nordaby RA, Vilarino JO, et al. The Endothelial Dysfunction. Cardiovasc Diabetol, 2006, 23, 5(1):4
14 Widlansky ME, et al. The Clinical implication of endothelial dysfunction. JACC, 2003, 42: 449
15 Ganz P, et al. Testing endothelial vasomotor function: NO, a multipotent molecule. Circulation, 2003,108: 2049
16 Targonsks PV, et al. coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation, 2003, 107:2805
17 Kali A, Janosi A. Endothelial function in high risk cardiovascular patients. Orv Hetil, 2006, 22, 147(3):99~106
18 Kawasaki M, Takatsu H, Noda T et al. Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. J Am Coll Cardiol, 2001,38(2):486~492
19 Muto S, Aiba A, Saito Y, et al. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet 2002; 11:1731~1742
20 Devuyst O, Persu A, Stoenoiu MS, et al. ENOS polymorphism and renal diseaseprogression in autosomal dominant polycystic kidney disease. Am J Kidney Dis, 2003, 41: 1124~1125
21 Simon A, Megnien JL, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia. Circulation, 1997, 96(7):2449~2452
22 Aminbakhsh A, Frohlich J, Mancini GB. Detection of early atherosclerosis with B mode carotid ultrasonography: assessment of a new quantitative approach. Clin Invest Med, 1999,22(6):265~274
23 Sass C, Zannad F, Herbeth B, et al. Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort. Atherosclerosis, 1998, 140(1):89~95
24 Kauma H, Paivansalo M, Savolainen MJ, et al. Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis. J Hypertens, 1996, 14(10):1183~1187
25 Bots ML, Launer LJ, Lindemans J, et al. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study. J Intern Med, 1997, 242(4):339~347
26 Megnien JL, Gariepy J, Saudubray JM, et al. Evidence of carotid artery wall hypertrophy in homozygous homocystinuria. Circulation, 1998,98(21):2276~2281
27 Coles KA, Plant AJ, Riley T et al. Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. Am J Cardiol, 1999, 84(7): 825~828
28 Nieto FJ, Adam E, Sorlie P, et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation, 1996, 94(5):922~927
29 Sorlie PD, Adam E, Melnick SL, et al. Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol, 1994, 42(1):33~37
30 Denarie N, Gariepy J, Chironi G, et al. Distribution of ultrasonographically- assessed dimensions of common carotid arteries in healthy adults of both sexes. Atherosclerosis, 2000,148(2):297~302
31 Demirovic J, Nabulsi A, Folsom AR, et al. Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation, 1993,88(6):2787~2793
32 Lamont D, Parker L, White M, et al. Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study. BMJ, 2000, 320(7230): 273~278
33 Schmidt-Trucksass AS, Grathwohl D, et al. Relation of leisure-time physical activity to structural and functional arterial properties of the common carotid artery in male subjects. Atherosclerosis, 1999,145(1):107~114
34 Bensen JT, Li R, Hutchinson RG, et al. Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities. Genet Epidemiol, 1999, 16(2): 165~178
35 Lindberg G, Rastam L, Lundblad A, et al. The association between serum sialic acid and asymptomatic carotid atherosclerosis is not related to antibodies to herpes type viruses or Chlamydia pneumoniae. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Int J Epidemiol, 1997, 26(6):1386~1391
36 Chen L, Patsch W, Boerwinkle E. HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid phenotypes and carotid artery atherosclerosis. Hum Genet, 1996,98(5):551
37 Saskia JV, Isabel F, Jos WRT, et al. Birthweight and arterial stiffness and blood pressure in adulthood—Results from the Amsterdam Growth and Health Longitudinal Study. Int J Epidem, 2004, 33(1):154~161
38 Stefan S, Annewieke WB, Clemens S, et al. Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation, 2004,110:344~348
39 Hausberg M, Kisters K, Kosch M, et al. Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients. Kidney Int, 1999,55:1104~1110
1 Simon A, Megnien JL, Levenson J. Coronary risk estimation and treatment of hypercholesterolemia. Circulation, 1997,96(7):2449-52
2 Aminbakhsh A, Frohlich J, Mancini GB. Detection of early atherosclerosis with B mode carotid ultrasonography: assessment of a new quantitative approach. Clin Invest Med, 1999,22(6):265-74
3 Greenland P, Abrams J, Aurigemma GP, et al. Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden: Writing Group III. Circulation, 2000 ,101(1):E16-22
4 Agewall S, Wikstrand J, Samuelsson O. The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. Risk Factor Intervention Study Group J Intern Med, 1994 ,236(6):651-9
5 Kanters SD, Algra A, van Leeuwen MS, et al. Reproducibility of in vivo carotid intima-media thickness measurements: a review. Stroke, 1997,28(3):665-71
6 Pignoli P, Tremoli E, Poli A, et al. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation, 1986,74(6):1399-406
7 Howard G, Sharrett AR, Heiss G et al. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. Stroke, 1993,24(9):1297-304
8 Gariepy J, Salomon J, Denarie N, et al. Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study. Arterioscler Thromb Vasc Biol, 1998,18(4):584-90
9 Graf S, Gariepy J, Massonneau M et al. Experimental and clinical validation of arterial diameter waveform and intimal media thickness obtained from B-mode ultrasound image processing. Ultrasound Med Biol, 1999,25(9):1353-63
10 Tang R, Hennig M, Thomasson B et al. Baseline reproducibility of B-mode ultrasonic measurement of carotid arte ry intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA). .J Hypertens, 2000,18(2):197-201
11 Denarie N, Gariepy J, Chironi G. et al. Distribution of ultrasonographically- assessed dimensions of common carotid arteries in healthy adults of both sexes. Atherosclerosis, 2000,148(2):297-302
12 Sharrett AR, Sorlie PD, Chambless Le et al. Relative importance of various risk factors for asymptomatic carotid atherosclerosis versus coronary heart disease incidence: the Atherosclerosis Risk in Communities Study. Am J Epidemiol, 1999,149(9):843-52
13 Mannami T, Baba S, Ogata J. Strong and significant relationships betweenaggregation of major coronary risk factors and the acceleration of carotid atherosclerosis in the general population of a Japanese city: the Suita Study. Arch Intern Med, 2000,160(15):2297-303
14 Zanchetti A, Crepaldi G, Bond MG. Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group. J Hypertens, 2001,19(1):79-88
15 Gariepy J, Simon A, Massonneau M, et al. Wall thickening of carotid and femoral arteries in male subjects with isolated hypercholesterolemia. PCVMETRA Group. Prevention Cardio-Vasculaire en Medecine du Travail. Atherosclerosis, 1995,113(2):141-51
16 Mykkanen L, Zaccaro DJ, O'Leary DH, et al. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke, 1997 ,28(9):1710-6
17 Persson J, Formgren J, Israelsson B, et al. Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb, 1994,14(2):261-4
18 Skoglund-Andersson C, Tang R, Bond MG, et al. LDL particle size distribution is associated with carotid intima-media thickness in healthy 50-year-old men. Arterioscler Thromb Vasc Biol, 1999 ,19(10):2422-30
19 Terry JG, Howard G, Mercuri M et al. Apolipoprotein E polymorphism is associated with segment-specific extracranial carotid artery intima-media thickening. Stroke, 1996,27(10):1755-9
20 Schreiner PJ, Heiss G, Tyroler HA, et al. Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol, 1996,16(3):471-8
21 Fukumoto M, Shoji T, Emoto M, et al. Antibodies against oxidized LDL and carotid artery intima-media thickness in a healthy population. Arterioscler Thromb Vasc Biol, 2000,20(3):703-7
22 Matthews KA, Owens JF, Kuller LH, et al. Are hostility and anxiety associated with carotid atherosclerosis in healthy postmenopausal women? Psychosom Med, 1998,60(5):633-8
23 Diez-Roux AV, Nieto FJ, Tyroler HA, et al. Social inequalities and atherosclerosis. The atherosclerosis risk in communities study. Am J Epidemiol, 1995,141(10):960-72
24 Levenson J, Gariepy J, Del-Pino M, et al. Association of plasma viscosity and carotid thickening in a French working cohort. Am J Hypertens, 2000,13(7):753-8
25 Bots ML, van Swieten JC, Breteler Mm, et al. Cerebral white matter lesions and atherosclerosis in the Rotterdam Study. Lancet, 1993,341(8855):1232-7
26 Crouse JR 3rd, Craven TE, Hagaman AP, et al. Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery. Circulation, 1995,92(5):1141-7
27 Cuspidi C, Lonati L, Sampieri L et al. Left ventricular concentric remodelling and carotid structural changes in essential hypertension.J Hypertens, 1996,14(12):1441-6
28 Mykkanen L, Zaccaro DJ, O'Leary DH, et al. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke, 1997 ,28(9):1710-6
29 Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997 ,96(5):1432-7
30 Hashimoto M, Eto M, Akishita M et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol, 1999 ,19(11):2795-800
31 Shinozaki K, Hattori Y, Suzuki M et al. Insulin resistance as an independent risk factor for carotid artery wall intima media thickening in vasospastic angina. Arterioscler Thromb Vasc Biol, 1997,17(11):3302-10
32 Olsen MH, Fossum E, Hjerkinn E et al. Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS,a LIFE sub study. Insulin Carotids US Scandinavia. J Hypertens, 2000,18(1):75-81
33 Haffner SM, D'Agostino R, Mykkanen L et al. Proinsulin and insulin concentrations in relation to carotid wall thickness: Insulin Resistance Atherosclerosis Study. Stroke, 1998,29(8):1498-503
34 Chen L, Patsch W, Boerwinkle E. HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid phenotypes and carotid artery atherosclerosis. Hum Genet, 1996,98(5):551-6
35 Sass C, Zannad F, Herbeth B, et al. Apolipoprotein E4, lipoprotein lipase C447 and angiotensin-I converting enzyme deletion alleles were not associated with increased wall thickness of carotid and femoral arteries in healthy subjects from the Stanislas cohort. Atherosclerosis, 1998,140(1):89-95
36 Kauma H, Paivansalo M, Savolainen MJ, et al. Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis. J Hypertens, 1996,14(10):1183-7
37 Bots ML, Launer LJ, Lindemans J, et al. Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study. J Intern Med, 1997,242(4):339-47
38 Megnien JL, Gariepy J, Saudubray JM, et al. Evidence of carotid artery wall hypertrophy in homozygous homocystinuria. Circulation, 1998,98(21):2276-81
39 Coles KA, Plant AJ, Riley T, et al. Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. Am J Cardiol, 1999,84(7):825-8
40 Nieto FJ, Adam E, Sorlie P, et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation, 1996,94(5):922-7
41 Sorlie PD, Adam E, Melnick SL, et al. Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol, 1994,42(1):33-7
42 Demirovic J, Nabulsi A, Folsom AR, et al. Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation,1993,88(6):2787-93
43 Lamont D, Parker L, White M, et al. Risk of cardiovascular disease measured by carotid intima-media thic kness at age 49-51: lifecourse study. BMJ, 2000,320(7230):273-8
44 Schmidt-Trucksass AS, Grathwohl D, et al. Relation of leisure-time physical activity to structural and functional arterial properties of the common carotid artery in male subjects. Atherosclerosis, 1999,145(1):107-14
45 Bensen JT, Li R, Hutchinson RG, et al. Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities. Genet Epidemiol, 1999,16(2):165-78
46 Lindberg G, Rastam L, Lundblad A, et al. The association between serum sialic acid and asymptomatic carotid atherosclerosis is not related to antibodies to herpes type viruses or Chlamydia pneumoniae. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Int J Epidemiol, 1997,26(6):1386-91
47 Rohde LE, Lee RT, Rivero J, et al. Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol, 1998,18(11):1765-70
48 Bizbiz L, Bonithon-Kopp C, Ducimetiere P, et al. Relation of serum elastase activity to ultrasonographically assessed carotid artery wall lesions and cardiovascular risk factors. The EVA study. Atherosclerosis, 1996,120(1-2):47-55
49 Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb, 1991,11(5):1245-9
50 Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol, 2000,151(5):478-87
51 O'Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.N Engl J Med, 1999,340(1):14-22
52 Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997,96(5):1432-7
53 Hodis HN, Mack WJ, LaBree L, et al. The role of carotid arterial intima-media thickness in predicting clinical coronary events.Ann Intern Med, 1998,128(4):262-9
54 Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation, 1995,92(7):1758-64
55 Mercuri M, Bond MG, Sirtori CR, et al. Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study. Am J Med, 1996,101(6):627-34
56 Crouse JR 3rd, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II) Am J Cardiol, 1995,75(7):455-9
57 de Groot E, Jukema JW, Montauban van, et al. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).J Am Coll Cardiol, 1998,31(7):1561-7
58 Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.Circulation, 1994,90(4):1679-87
59 Smilde TJ, van Wissen S, Wollersheim H, et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet, 2001,357(9256):577-81
60 Borhani NO, Mercuri M, Borhani PA, et al. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.JAMA, 1996,276(10):785-91
61 Zanchetti A, Rosei EA, Dal Palu C, et al. The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens, 1998,16(11):1667-76
62 Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation, 2000,102(13):1503-10
63 Lonn E, Yusuf S, Dzavik V, et al. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation, 2001,103(7):919-25
64 Blankenhorn DH, Selzer RH, Crawford DW, et al. Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation, 1993,88(1):20-8
65 Hodis HN, Mack WJ, LaBree L, et al. Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled clinical trial. Ann Intern Med, 1996,124(6):548-56
66 MacMahon S, Sharpe N, Gamble G, et al. Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group. Circulation, 1998,97(18):1784-90
67 Simon A, Gariepy J, Moyse D, et al. Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes. Circulation, 2001,103(24):2949-54
68 Linhart A, Gariepy J, Giral P, et al. Carotid artery and left ventricular structural relationship in asymptomatic men at risk for cardiovascular disease. Atherosclerosis, 1996,127(1):103-12
69 Cooke JP. The endothelium: a new target for therapy. Vasc Med, 2000;5(1):49-53
70 Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet,1992, 340(8828):1111-5
71 chachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease.Circulation, 2000, 1(16):1899-906
72 O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.Circulation, 1997, 95(5):1126-31
73 Vogel RA. Cholesterol lowering and endothelial function. Am J Med, 1999, 107(5):479-87
74 Mombouli JV, Vanhoutte PM. Endothelial dysfunction: from physiology to therapy.J Mol Cell Cardiol, 1999, 31(1):61-74
75 YangY, Loscalzo J. Regulation of tissue factor expression in human microvascular e ndothelial cells by nitric oxide.Circulation, 2000, 101(18):2144-8
76 Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, 288(5789):373-6
77 ai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress.Circ Res. 2000, 87(10):840-4
78 Pepine CJ. Clinical implications of endothelial dysfunction. Clin Cardiol, 1998, 21(11):795-9
79 Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.Circulation, 2000, 7;101(9):948-54
80 aitakari OT, Celermajer DS. Testing for endothelial dysfunction. Ann Med, 2000, 32(5):293-304
81 Wang J, Brown MA, Tam SH, et al. Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol, 1997, 24(6):418-20
82 Huggins GS, Pasternak RC, Alpert NM, et al. Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. Circulation,1998, 98(13):1291-6
83 Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation, 1989, 79(1):93-100
84 Dimmeler S, Fleming I, Fisslthaler B, et al. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature, 1999,399(6736):601-5
85 Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation. Clin Sci (Lond), 2000, 99(4):261-7
86 Vogel RA. Measurement of endothelial function by brachial artery flow-mediated vasodilation. Am J Cardiol, 2001, 88(2A):31E-34E
87 Gokce N, Holbrook M, Hunter LM, et al. Acute effects of vasoactive drug treatment on brachial artery reactivity. J Am Coll Cardiol, 2002, 40(4):761-5
88 Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol, 1995, 26(5):1235-41
89 Celermajer DS, Sorensen KE, Bull C, et al. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol, 1994, 24(6):1468-74
90 Enderle MD, Schroeder S, Ossen R, Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease. Heart, 1998, 80(4):349-54
91 Kuvin JT, Patel AR, Sliney KA, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol, 2001, 38(7):1843-9
92 Gokce N, Keaney JF Jr, Hunter LM, Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation, 2002, 105(13):1567-72
93 Woodman RJ, Playford DA, Watts GF, et al. Improved analysis of brachial artery ultrasound using a novel edge-detection software system.J Appl Physiol, 2001,91(2):929-37
94 Bressler B, Chan S, Mancini GB. Temporal response of brachial artery dilation after occlusion and nitroglycerin. Am J Cardiol, 2000, 85(3):396-400, A10
95 van der Heijden-Spek JJ, Staessen JA, Fagard RH, et al. Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study.Hypertension, 2000, 35(2):637-42
96 Herrington DM, Fan L, Drum M, et al. Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk, 2001, 8(5):319-28
97 Lieberman EH, Gerhard MD, Uehata A, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med, 1994, 121(12):936-41
98 Ringqvist A, Caidahl K, Petersson AS, Wennmalm A. Diurnal variation of flow-mediated vasodilation in healthy premenopausal women.Am J Physiol Heart Circ Physiol, 2000, 279(6):H2720-5
99 Etsuda H, Takase B, Uehata A, Morning attenuation of endothelium-dependent, flow-mediated dilation in healthy young men: possible connection to morning peak of cardiac events? Clin Cardiol, 1999, 22(6):417-21
100 Perregaux D, Chaudhuri A, Rao S. Brachial vascular reactivity in blacks.Hypertension, 2000, 36(5):866-71