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Circulation. 2001;104:191-196

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(Circulation. 2001;104:191.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients

Francesco Perticone, MD; Roberto Ceravolo, MD; Arturo Pujia, MD; Giorgio Ventura, MD; Saverio Iacopino, MD; Angela Scozzafava, MD; Alessandro Ferraro, MD; Massimo Chello, MD; Pasquale Mastroroberto, MD; Paolo Verdecchia, MD; Giuseppe Schillaci, MD

From the Internal Medicine and Cardiovascular Diseases Unit (F.P., R.C., A.P, G.V., S.I., A.S., A.F.) and Cardiovascular Surgery Unit (M.C., P.M.), Department of Medicina Sperimentale e Clinica "G. Salvatore," University of Catanzaro Magna Græcia, Catanzaro, Italy, and Cardiologia e Fisiopatologia Cardiovascolare (P.V.) and Medicina Interna (G.S.), Angiologia e Malattie da Arteriosclerosi, University of Perugia, Perugia, Italy.

Correspondence to Francesco Perticone, MD, Department of Medicina Sperimentale e Clinica, Policlinico Mater Domini, Via Tommaso Campanella, 88100 Catanzaro, Italy. E-mail perticone{at}unicz.it


*    Abstract
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Background— Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown.

Methods and Results— Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure.

Conclusions— Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.


Key Words: endothelium • cardiovascular diseases • hypertension


*    Introduction
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Many experimental and clinical studies have shown a strong link between atherosclerosis and cardiovascular risk.15 Atherosclerosis is a progressive process that initially involves endothelial dysfunction and accumulation and peroxidation of intimal lipids, followed by release of inflammatory cells and growth factors, resulting in vascular smooth muscle cell (VSMC) proliferation and collagen matrix production.68 The normal endothelium—an autocrine, paracrine, and endocrine organ—plays a key role in regulating vascular tone, thrombogenesis, lipid breakdown, inflammation, and vessel growth.911 There is growing evidence that endothelial dysfunction may influence the progression of atherosclerotic lesions.8,11,12

Traditional risk factors such as hypertension,1315 cigarette smoking,16 diabetes,17 age,18 and hypercholesterolemia19 induce coronary and brachial artery endothelial dysfunction owing to decreased bioavailability of nitric oxide (NO). A dysfunctioning endothelium may lose its ability to exert its protective effect on the vascular system by reducing its antiatherosclerotic and antithrombotic actions and thus playing a key pathophysiological role in the development and progression of the atherosclerotic process.

Endothelial function is most commonly measured as the vasodilating response to physical or pharmacological stimuli such as shear stress, acetylcholine (ACh), bradykinin, thrombin, substance P, and serotonin.11 Each agonist acts through a cellular membrane receptor, with signal transduction operating through G proteins. In this way, it has recently been demonstrated that depressed coronary endothelial function in humans may be associated with myocardial ischemia.20,21 Furthermore, cholesterol-lowering agents significantly improve outcomes in secondary35 and primary22 prevention, and it has been speculated that these beneficial effects may be mediated, at least in part, by an improvement in endothelial dysfunction. More recently, it has been shown that coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular events rate.23,24 Thus, coronary endothelial vasoreactivity may provide diagnostic and prognostic information in patients at risk for coronary artery disease (CAD). At present, however, no data exist on the prognostic significance of forearm endothelial dysfunction evaluated by strain-gauge plethysmography.

On the basis of these observations, the aim of this study was to evaluate prospectively the outcomes in initially untreated and uncomplicated hypertensive patients with forearm endothelial dysfunction.


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Study Population
A total of 225 outpatients at Catanzaro University Hospital, 106 men and 119 women 35 to 54 years of age (mean±SD, 46.4±5.3 years) with well-documented history of essential hypertension and complete follow-up data who were enrolled between March 1992 and April 2000, are included in the present analysis. All patients were white and underwent physical examination and review of their medical histories. Causes of secondary hypertension were excluded by clinical and biochemical tests. At the time of vascular evaluation, none of the patients had a history or clinical evidence of angina, myocardial infarction (MI), valvular heart disease, diabetes, hyperlipidemia, peripheral vascular disease, coagulopathy, or any disease predisposing them to vasculitis or Raynaud’s phenomenon. The following risk factors for atherosclerosis were assessed at the time of the first evaluation: glucose, cholesterol, triglycerides, smoking, and a positive family history of CAD. Body mass index ranged between 24.0 and 28.0 kg/m2. All participants had never been treated with antihypertensive drugs.

The local ethics committee approved the study, and all participants gave written, informed consent for all procedures.

Blood Pressure Measurements
A physician measured blood pressure (BP) 3 times using a mercury sphygmomanometer with the patient seated for >=5 minutes, and the mean of the last 2 measurements was used. Hypertension was defined as systolic BP >=160 mm Hg, diastolic BP >=95 mm Hg, or both.

Ambulatory BP monitoring was obtained with A&D TM 2420 and A&D TM 2421 (Takeda) recorders. Recordings were taken every 10 minutes during the day (from 7 AM to 11 PM) and every 20 minutes during the night (from 11 PM to 7 AM). The patients were invited to observe these periods of rest and activity closely.

Vascular Function
All studies were performed at 9 AM after subjects had fasted overnight, with the subjects lying supine in a quiet, air-conditioned room (22°C to 24°C); the protocol previously described by Panza et al13 and subsequently used by our group15,25,26 was employed for the present study. Subjects were requested to refrain from smoking >=4 hours before starting the examination. All patients underwent measurement of forearm blood flow (FBF) and BP during intra-arterial infusion of saline, ACh, and sodium nitroprusside (SNP) at increasing doses. All participants rested 30 minutes after artery cannulation to reach a stable baseline before data collection; measurements of FBF and vascular resistance (VR), expressed in units, were repeated every 5 minutes until stable. Endothelium-dependent and -independent vasodilation was assessed by a dose-response curve to intra-arterial ACh infusions (7.5, 15, and 30 µg · mL-1 · min-1, each for 5 minutes) and SNP infusions (0.8, 1.6, and 3.2 µg · mL-1 · min-1, each for 5 minutes), respectively. The sequence of administration of ACh and SNP was randomized to avoid any bias related to the order of drug infusion. The drug infusion rate, adjusted for forearm volume of each subject, was 1 mL/min.

Follow-Up and Cardiovascular Events
Follow-up included periodic control visits in the outpatient clinic of our university hospital for most patients. To improve long-term follow-up, a questionnaire was also mailed to family physicians. All patients were treated with the purpose of reducing clinic BP to <140/90 mm Hg through standard lifestyle and pharmacological treatment. Antihypertensive agents included diuretics, ß-blockers, ACE inhibitors, calcium channel blockers, angiotensin II receptor antagonists, and {alpha}1-blockers alone or in various associations. Contact with family physicians and telephone interviews were periodically undertaken to assess the incidence of major cardiovascular events. All information regarding potential cardiovascular events was validated by source data, including hospital record forms, death certificates, and other available original documents.

The following cardiovascular events were assessed during long-term follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, transient cerebral ischemic attack (TIA), unstable angina, coronary revascularization procedures (bypass surgery or angioplasty), and symptomatic aortoiliac occlusive disease documented with angiography. MI was defined as an increase in creatine kinase exceeding 2-fold the upper limit and new ST elevation >=2 leads. Unstable angina was defined by typical chest pain associated with ischemic ECG changes and successively documented by provocative tests (treadmill exercise test or/and stress echocardiography, myocardial scintigraphy, or coronary angiography). TIA was defined by physician diagnosis of any sudden focal neurological deficit that cleared completely in <24 hours.

Most patients were referred periodically to our university hospital for clinical and BP control and other diagnostic procedures.

Drugs
ACh (Sigma) was obtained from commercially available sources and freshly diluted to the desired concentration by the addition of saline. SNP (Malesci) was diluted in 5% glucose solution immediately before each infusion and protected from light with aluminum foil.

Statistical Analysis
Standard descriptive and comparative analyses were undertaken. Events rate is reported as the number of events per 100 patient-years based on the ratio of the number of events observed to the total number of patient-years of exposure up to the terminating event or censor. For the patients without events, the date of censor was that of the last contact with the patient. For patients who experienced multiple events, survival analysis was restricted to the first event. Survival curves were estimated by use of the Kaplan-Meier product-limit method and compared by using the Mantel (log-rank) test. The effect of prognostic factors on survival was evaluated by use of the stepwise Cox semiparametric regression model. The assumption of linearity for the Cox model was tested through visual inspection, and no violation of proportional hazards was found. We tested the following variables: age, sex, body mass index, triglycerides, serum cholesterol, smoking habits (previous or current smokers or never smoked), and clinic and ambulatory BP. FBF was tested either as a continuous variable or by tertiles. Significant differences were assumed to be at P<0.05. All group data are reported as mean±SD.


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Study Population
Intra-arterial infusion of ACh caused a dose-dependent and significant increase in FBF and decrease in forearm VR. The FBF increments from basal at the 3 incremental doses of ACh were 1.9±1.9 mL · 100 mL-1 tissue · min-1 (55%), 3.0±1.9 mL · 100 mL-1 tissue · min-1 (142%), and 10.8±6.3 mL · 100 mL-1 tissue · min-1 (293%). At the highest dose of ACh (30 µg/min), FBF increased to 14.6±9.0 mL · 100 mL-1 tissue · min-1, and VR decreased to 10.1±5.0 U. Intra-arterial infusion of ACh caused no changes in BP or heart rate values. The peak percent increase on FBF during ACh infusion was considered both as a continuous variable and according to specific tertiles: from a 30% to 184% increase from basal (first tertile), from a 185% to 333% increase from basal (second tertile), and from a 339% to 760% increase from basal (third tertile).

During SNP infusion, a significant increase in FBF and a decrease in forearm VR were observed, but no significant differences were found between tertiles. Peak increases in FBF in the 3 tertiles were 346±89%, 345±90%, and 358±90%, respectively (P=0.614 by ANOVA); the increases in VR were 7.8±2.8, 7.4±2.3, and 7.2±1.9 (P=0.287 by ANOVA).

Table 1 reports the clinical, humoral, and hemodynamic characteristics of the study population by tertiles of ACh-stimulated FBF. In the total population, the baseline clinic and ambulatory BP values were 158/95±13/7 and 148/89±9/7 mm Hg. After 6 months and 1 year of treatment, the clinic BP values decreased to 140/87±12/8 and 136/84±10/9 mm Hg, respectively. The BP reduction was similar in the 3 tertiles. Finally, the different treatment strategy in the study population, divided by ACh tertiles, is reported in Table 2.


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Table 1. Subject Characteristics by Tertiles of Peak Percent Increase in FBF During ACh Infusions


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Table 2. Antihypertensive Drugs in the Study Population by Tertiles of ACh-Stimulated FBF

Outcome Events
During a mean follow-up period of 31.5±23.9 months (range, 4 to 84 months), there were 29 new cardiovascular morbid events (4.9 events per 100 patient-years) at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level, as reported in Table 3. In particular, there were 6 patients with MI (1 fatal), 10 with unstable angina pectoris, 3 with coronary revascularization procedures, 7 with stroke (1 fatal), 2 with transient cerebral ischemia, and 1 with new-onset aortoiliac occlusive disease. Indications for the revascularization procedures were put forward by physicians not involved in this study.


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Table 3. Cardiovascular Events in the Study Population by Tertiles of ACh-Stimulated FBF

As reported in Figure 1, the rate of total (fatal plus nonfatal) cardiovascular events (per 100 patient-years) was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. Event-free survival curves in the 3 tertiles of FBF are graphically reported in Figure 2. The cumulative cardiovascular events rate in the first tertile was 57.2% at 7 years compared with a cumulative rate of 14.4% in the third tertile (P=0.0012, log-rank test). Differences across tertiles remained significant (P=0.0166) after exclusion of soft cardiovascular events (TIA, unstable angina, coronary revascularization procedures, and aortoiliac occlusive disease).



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Figure 1. Rate of total (fatal and nonfatal) cardiovascular events and mean values of percent increase in ACh-stimulated FBF in 3 tertiles.



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Figure 2. Kaplan-Meier analysis. Event-free survival curves in hypertensive patients (pts) were subdivided into tertiles of FBF.

Finally, when we divided the study population in the SNP subgroups, the rate of total cardiovascular events (per 100 patient-years) was 4.3, 5.9, and 4.5 in the first, second, and third tertiles of peak percent increase in FBF (log-rank=1.664, P=0.44).

Multivariate Analysis
To identify the effect of endothelial dysfunction and the classic risk factors for atherosclerosis as independent predictors of cardiovascular events, we performed a multivariate Cox regression analysis. As shown in Table 4, the only independent predictors of cardiovascular events were mean 24-hour ambulatory BP and the peak percent increase in FBF. In the first tertile of peak percent increase in FBF, event risk was about twice that in the third tertile (adjusted hazard ratio, 2.084; 95% CI, 1.249 to 3.477; P=0.0049). When the peak percent increase in FBF entered the equation as a continuous variable, results did not change (adjusted hazard ratio for every 1% increase in FBF, 0.994; 95% CI, 0.991 to 0.998; P=0.0014). A marked risk gradient for adverse cardiovascular events was noted across the tertiles of FBF after adjustment for other covariates.


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Table 4. Independent Predictors of Cardiovascular Morbid Events (Cox Model)


*    Discussion
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This study shows for the first time that forearm endothelial dysfunction is a marker for future cardiovascular morbid events in initially untreated and uncomplicated subjects with essential hypertension. This relation, statistically significant and clinically consistent, persisted after adjustment for established risk factors for atherosclerosis. Results did not change when FBF changes were analyzed as a continuous variable or divided by tertiles. We used the tertiles partition because currently there is no agreed-on definition of normal FBF change.

Our data are in agreement with those recently reported by Suwaidi et al23 and Schächinger et al,24 who demonstrated a link between endothelial coronary dysfunction and subsequent cardiovascular events. The basic mechanisms by which forearm endothelial dysfunction may predispose to subsequent cardiovascular morbid events are largely unknown. The reduced NO bioavailability that characterizes the endothelial dysfunction may induce important steps in the appearance and progression of the atherosclerotic lesions, including monocyte and leukocyte adhesion and platelet-vessel wall interaction.68,27 NO also reduces vascular tone, decreases endothelial permeability,28 and inhibits VSMC migration and proliferation in vitro and in vivo.68 Thus, a persistent decrease in NO availability might represent a pivotal basic mechanisms predisposing to clinical adverse events associated to human atherosclerosis.

Hypertension, Endothelial Function, and Atherosclerosis
An abnormal endothelial function has been implicated in the pathophysiology of essential hypertension.1214 Endothelial cells produce some potent vasoactive substances such as the vasodilator molecule NO and the vasoconstrictor peptide endothelin-1. Reduction of NO synthesis and/or its increased inactivation by oxygen free radicals may account for the increased VR in hypertensive patients and contribute to clinical consequences of this condition such as vascular and cardiac hypertrophy, CAD, and stroke. The mechanisms underlying reduced NO availability in human essential hypertension are almost certainly multifactorial; however, there is substantial evidence that NO bioavailability is reduced because of oxidative inactivation by excessive production of superoxide anions.12,29 In the vascular wall, an increase in oxidative stress is thought to modify several important physiological functions. Regulation of vascular tone and blood flow, increased platelet and monocyte adhesion to the endothelium, and control of cellular growth are strongly influenced by reactive oxygen species. These phenomena ultimately modulate vessel diameter and remodeling and formation of atherosclerotic lesions.68,27,28 These vascular abnormalities that induce structural and mechanical changes may offer important insights into the development and progression of vasculature-initiated end-organ damage in cardiovascular diseases. Thus, a depressed endothelium-dependent vasodilation may be considered an earlier modification, present in essential hypertension and other cardiovascular risk factors, that may promote and develop the coronary and extracoronary atherosclerotic process by stimulating the proliferation of VSMCs and fibroblasts. Finally, chronic endothelial dysfunction often may be associated with an erosion and/or rupture of the atherosclerotic plaque that promotes plaque instability and acute vascular syndromes.8

Evaluation of End Points in Hypertension
The benefits of antihypertensive treatment in decreasing both cerebrovascular and cardiac events have been substantiated by meta-analyses of major randomized outcome trials.3032 Cardiovascular mortality, MI, and stroke remain undisputed hard end points in intervention trials. However, intermediate end points are frequently used as substitutes for the hard end points. These intermediate or substitute end points are sometimes referred to as surrogate end points, and it is reasonable to consider BP itself the chief validated surrogate marker of cardiovascular outcome in hypertensive patients. Nevertheless, event-based trials of antihypertensive therapy did not determine whether pharmacological treatment influences the development and progression of the atherosclerotic process.

The coronary and extracoronary endothelium of hypertensive patients has depressed ability to induce vascular relaxation because of an impaired response or increased inactivation of NO. Endothelial dysfunction may thus play a key role in myocardial, cerebral, and renal complications of hypertensive status. In this context, our data suggest a direct link between endothelial dysfunction and hypertensive vascular complications. Our findings imply that ACh-stimulated vasodilation could be considered a surrogate end point for assessing the time course of atherosclerosis and its clinical consequences. This concept may be reinforced by our previously published findings demonstrating a strong and significant relationship between echocardiographic cardiac mass and endothelial dysfunction.25 In fact, both cardiac hypertrophy and depressed ACh-stimulated vasodilation in hypertensive patients may be considered indicative of an increased risk for subsequent cardiovascular events. Finally, the demonstration that hypertension-associated endothelial dysfunction26,33 and cardiac hypertrophy34,35 may be reversed by a pharmacological treatment may represent a new target for therapeutic intervention in essential hypertension.

Received January 3, 2001; revision received April 12, 2001; accepted April 14, 2001.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
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*References
 
1. Anderson M, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from Framingham Study. JAMA. 1987; 257: 2176–2180.[Abstract/Free Full Text]

2. Multiple Risk Factors Intervention Trial Research Group Mortality rates after 10.5 years for participant in the Multiple Risk Factors Intervention Trial: findings related to a priori hypothesis of the trial. JAMA. 1990; 263: 1795–1801.[Abstract/Free Full Text]

3. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344: 1383–1389.[Medline] [Order article via Infotrieve]

4. Sacks FM, Pfeffer MA, Moye LA, et al. The effects of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996; 335: 1001–1009.[Abstract/Free Full Text]

5. Long Term Intervention with Pravastatin in Patients With Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1349–1357.[Abstract/Free Full Text]

6. Fuster V, Badimon L, Badimon JJ, et al. The pathogenesis of coronary artery disease. N Engl J Med. 1992; 326: 242–250.[Medline] [Order article via Infotrieve]

7. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1998; 334: 1349–1357.[Abstract/Free Full Text]

8. Vogel RA. Cholesterol lowering and endothelial function. Am J Med. 1999; 107: 479–487.[Medline] [Order article via Infotrieve]

9. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288: 373–376.[Medline] [Order article via Infotrieve]

10. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990; 323: 27–36.[Medline] [Order article via Infotrieve]

11. Lüscher TF, Vanhoutte PM. The Endothelium: Modulator of Cardiovascular Function. Boca Raton, Fla: CRC Press; 1990.

12. Quyyumi AA. Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med. 1998; 105: 32S–39S.[Medline] [Order article via Infotrieve]

13. Panza JA, Quyyumi AA, Brush JE, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990; 323: 22–27.[Abstract]

14. Taddei S, Virdis A, Mattei P, et al. Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension. 1993; 21: 929–933.[Abstract/Free Full Text]

15. Perticone F, Ceravolo R, Maio R, et al. Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never-treated hypertensive patients. Hypertension. 1998; 31: 900–905.[Abstract/Free Full Text]

16. Zeiher AM, Schächinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilation function. Circulation. 1995; 92: 1094–1100.[Abstract/Free Full Text]

17. Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent coronary arterial vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993; 88: 2510–2516.[Abstract/Free Full Text]

18. Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995; 91: 1981–1987.[Abstract/Free Full Text]

19. Creager MA, Cooke JP, Mendelson ME, et al. Impaired vasodilation of forearm resistance vessel in hypercholesterolemic humans. J Clin Invest. 1990; 86: 228–234.

20. Zeier AM, Krause T, Schächinger V, et al. Impaired endothelium-dependent vasodilation of coronary resistance vessel is associated with exercise-induced ischemia. Circulation. 1995; 91: 2345–2352.[Abstract/Free Full Text]

21. Hasdai D, Gibbons RJ, Holmes DR Jr, et al. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation. 1997; 96: 3390–3395.[Abstract/Free Full Text]

22. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995; 333: 1301–1307.[Abstract/Free Full Text]

23. Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000; 101: 948–954.[Abstract/Free Full Text]

24. Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000; 101: 1899–1906.[Abstract/Free Full Text]

25. Perticone F, Maio R, Ceravolo R, et al. Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients. Circulation. 1999; 99: 1991–1996.[Abstract/Free Full Text]

26. Perticone F, Ceravolo R, Maio R, et al. Calcium antagonist isradipine improves abnormal endothelium-dependent vasodilation in never treated hypertensive patients. Cardiovasc Res. 1999; 41: 299–306.[Abstract/Free Full Text]

27. de Graaf JC, Banga JD, Moncada S, et al. Nitric oxide inhibitor of platelet adhesion under flow conditions. Circulation. 1992; 85: 2284–2290.[Abstract/Free Full Text]

28. Draijer R, Atsma DE, van der Laarse A, et al. cGMP and nitric oxide modulate thrombin-induced endothelial permeability: regulationvia different pathway in human aortic and umbilical vein endothelial cells. Circ Res. 1995; 76: 199–208.[Abstract/Free Full Text]

29. Taddei S, Virdis A, Ghiadoni L, et al. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1998; 97: 2222–2229.[Abstract/Free Full Text]

30. McMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease, part 1: prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335: 765–774.[Medline] [Order article via Infotrieve]

31. Collins R, Peto R, McMahon S, et al. Blood pressure, stroke, and coronary heart disease, part 2: short-term reductions in blood pressure: overview of randomized drug trials in their epidemiological context. Lancet. 1990; 335: 827–838.[Medline] [Order article via Infotrieve]

32. Blood Pressure Lowering Treatment Trialists Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomized trials. Lancet. 2000; 355: 1955–1964.[Medline] [Order article via Infotrieve]

33. Taddei S, Virdis A, Ghiadoni L, et al. Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension. 1997; 30: 1606–1612.[Abstract/Free Full Text]

34. Dahlöf B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients: a meta-analysis of 109 treatment studies. Am J Hypertens. 1992; 5: 95–110.[Medline] [Order article via Infotrieve]

35. Verdecchia P, Schillaci G, Borgioni C, et al. Prognostic significance of serial changes in left ventricular mass in essential hypertension. Circulation. 1998; 97: 48–54.[Abstract/Free Full Text]




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Home page
Eur J Heart FailHome page
M. Klosinska, T. Rudzinski, P. Grzelak, L. Stefanczyk, J. Drozdz, and M. Krzeminska-Pakula
Endothelium-dependent and -independent vasodilation is more attenuated in ischaemic than in non-ischaemic heart failure
Eur J Heart Fail, August 1, 2009; 11(8): 765 - 770.
[Abstract] [Full Text] [PDF]


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StrokeHome page
A. Gunarathne, J. V. Patel, S. Kausar, B. Gammon, E. A. Hughes, and G. Y.H. Lip
Glycemic Status Underlies Increased Arterial Stiffness and Impaired Endothelial Function in Migrant South Asian Stroke Survivors Compared to European Caucasians: Pathophysiological Insights From the West Birmingham Stroke Project
Stroke, July 1, 2009; 40(7): 2298 - 2306.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Seddon, N. Melikian, R. Dworakowski, H. Shabeeh, B. Jiang, J. Byrne, B. Casadei, P. Chowienczyk, and A. M. Shah
Effects of Neuronal Nitric Oxide Synthase on Human Coronary Artery Diameter and Blood Flow In Vivo
Circulation, May 26, 2009; 119(20): 2656 - 2662.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
D. O. McCall, C. P. McGartland, M. C. McKinley, C. C. Patterson, P. Sharpe, D. R. McCance, I. S. Young, and J. V. Woodside
Dietary Intake of Fruits and Vegetables Improves Microvascular Function in Hypertensive Subjects in a Dose-Dependent Manner
Circulation, April 28, 2009; 119(16): 2153 - 2160.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. Wang, S. Strandgaard, J. Iversen, and C. S. Wilcox
Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R195 - R200.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
J. Rodes-Cabau, M. Noel, A. Marrero, D. Rivest, A. Mackey, C. Houde, E. Bedard, E. Larose, S. Verreault, M. Peticlerc, et al.
Atherosclerotic Burden Findings in Young Cryptogenic Stroke Patients With and Without a Patent Foramen Ovale
Stroke, February 1, 2009; 40(2): 419 - 425.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
D. H. J. Thijssen, L. M. Bullens, M. M. van Bemmel, E. A. Dawson, N. Hopkins, T. M. Tinken, M. A. Black, M. T. E. Hopman, N. T. Cable, and D. J. Green
Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans
Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H57 - H64.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
S. Caron and B. Staels
Apolipoprotein CIII: A Link Between Hypertriglyceridemia and Vascular Dysfunction?
Circ. Res., December 5, 2008; 103(12): 1348 - 1350.
[Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
R. Muniyappa, G. Hall, T. L Kolodziej, R. J Karne, S. K Crandon, and M. J Quon
Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension
Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1685 - 1696.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
Y.-H. Chan, K.-K. Lau, K.-H. Yiu, S.-W. Li, H.-T. Chan, D. Y.-T. Fong, S. Tam, C.-P. Lau, and H.-F. Tse
Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke
Eur. Heart J., November 2, 2008; 29(22): 2800 - 2807.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
D. H. J. Thijssen, E. A. Dawson, M. A. Black, M. T. E. Hopman, N. T. Cable, and D. J. Green
Heterogeneity in conduit artery function in humans: impact of arterial size
Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1927 - H1934.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
D. H. J. Thijssen, M. M. van Bemmel, L. M. Bullens, E. A. Dawson, N. D. Hopkins, T. M. Tinken, M. A. Black, M. T. E. Hopman, N. T. Cable, and D. J. Green
The impact of baseline diameter on flow-mediated dilation differs in young and older humans
Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1594 - H1598.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
T. Sugiura, T. Kondo, Y. Kureishi-Bando, Y. Numaguchi, O. Yoshida, Y. Dohi, G. Kimura, R. Ueda, T. J. Rabelink, and T. Murohara
Nifedipine Improves Endothelial Function: Role of Endothelial Progenitor Cells
Hypertension, September 1, 2008; 52(3): 491 - 498.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. Bobik
Apolipoprotein CIII and Atherosclerosis: Beyond Effects on Lipid Metabolism
Circulation, August 12, 2008; 118(7): 702 - 704.
[Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
B. Fernhall and S. Agiovlasitis
Arterial function in youth: window into cardiovascular risk
J Appl Physiol, July 1, 2008; 105(1): 325 - 333.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
F. Perticone, A. Sciacqua, M. Perticone, I. Laino, S. Miceli, I. Care', G. Galiano Leone, F. Andreozzi, R. Maio, and G. Sesti
Low-Plasma Insulin-Like Growth Factor-I Levels Are Associated with Impaired Endothelium-Dependent Vasodilatation in a Cohort of Untreated, Hypertensive Caucasian Subjects
J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2806 - 2810.
[Abstract] [Full Text] [PDF]


Home page
Postgrad. Med. J.Home page
D Tousoulis, M Charakida, and C Stefanadis
Endothelial function and inflammation in coronary artery disease
Postgrad. Med. J., July 1, 2008; 84(993): 368 - 371.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
G. L. Pierce, S. D. Beske, B. R. Lawson, K. L. Southall, F. J. Benay, A. J. Donato, and D. R. Seals
Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults
Hypertension, July 1, 2008; 52(1): 72 - 79.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. D. Seddon, P. J. Chowienczyk, S. E. Brett, B. Casadei, and A. M. Shah
Neuronal Nitric Oxide Synthase Regulates Basal Microvascular Tone in Humans In Vivo
Circulation, April 15, 2008; 117(15): 1991 - 1996.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
V. Stangl, V. Witzel, G. Baumann, and K. Stangl
Current diagnostic concepts to detect coronary artery disease in women
Eur. Heart J., March 2, 2008; 29(6): 707 - 717.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
F. Perticone, R. Maio, A. Sciacqua, F. Andreozzi, G. Iemma, M. Perticone, C. Zoccali, and G. Sesti
Endothelial Dysfunction and C-Reactive Protein Are Risk Factors for Diabetes in Essential Hypertension
Diabetes, January 1, 2008; 57(1): 167 - 171.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
M. Briet, C. Collin, S. Laurent, A. Tan, M. Azizi, M. Agharazii, X. Jeunemaitre, F. Alhenc-Gelas, and P. Boutouyrie
Endothelial Function and Chronic Exposure to Air Pollution in Normal Male Subjects
Hypertension, November 1, 2007; 50(5): 970 - 976.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
Y.-H. Chan, K.-K. Lau, K.-H. Yiu, S.-W. Li, H.-T. Chan, S. Tam, X.-O. Shu, C.-P. Lau, and H.-F. Tse
Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden
Am. J. Clinical Nutrition, October 1, 2007; 86(4): 938 - 945.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
A. Philpott and T. J. Anderson
Reactive Hyperemia and Cardiovascular Risk
Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2065 - 2067.
[Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
A. L. Huang, A. E. Silver, E. Shvenke, D. W. Schopfer, E. Jahangir, M. A. Titas, A. Shpilman, J. O. Menzoian, M. T. Watkins, J. D. Raffetto, et al.
Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery
Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2113 - 2119.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Coll. Nutr.Home page
S. M. Shenouda and J. A. Vita
Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function
J. Am. Coll. Nutr., August 1, 2007; 26(4): 366S - 372S.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
E. Zittan, M. Preis, I. Asmir, A. Cassel, N. Lindenfeld, S. Alroy, D. A. Halon, B. S. Lewis, A. Shiran, J. E. Schliamser, et al.
High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H860 - H865.
[Abstract] [Full Text] [PDF]


Home page
Diabetes and Vascular Disease ResearchHome page
S. J Hamilton, G. T Chew, and G. F Watts
Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus
Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 89 - 102.
[Abstract] [PDF]


Home page
Diabetes CareHome page
R. E. Schmieder, C. Delles, A. Mimran, J. P. Fauvel, and L. M. Ruilope
Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes
Diabetes Care, June 1, 2007; 30(6): 1351 - 1356.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. Yeboah, J. R. Crouse, F.-C. Hsu, G. L. Burke, and D. M. Herrington
Brachial Flow-Mediated Dilation Predicts Incident Cardiovascular Events in Older Adults: The Cardiovascular Health Study
Circulation, May 8, 2007; 115(18): 2390 - 2397.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
A. Barac, U. Campia, and J. A. Panza
Methods for Evaluating Endothelial Function in Humans
Hypertension, April 1, 2007; 49(4): 748 - 760.
[Full Text] [PDF]


Home page
Cardiovasc ResHome page
T. Minamino and M. Hori
Protecting endothelial function: A novel therapeutic target of ATP-sensitive potassium channel openers
Cardiovasc Res, February 1, 2007; 73(3): 448 - 449.
[Full Text] [PDF]


Home page
DiabetesHome page
W. S. Waring, J. A. McKnight, D. J. Webb, and S. R.J. Maxwell
Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers
Diabetes, November 1, 2006; 55(11): 3127 - 3132.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
C. J. Boos, G. Y.H. Lip, and A. D. Blann
Circulating Endothelial Cells in Cardiovascular Disease
J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
S. Wassmann, N. Werner, T. Czech, and G. Nickenig
Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells
Circ. Res., October 13, 2006; 99(8): E74 - E83.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
C. M. McEniery, S. Wallace, I. S. Mackenzie, B. McDonnell, Yasmin, D. E. Newby, J. R. Cockcroft, and I. B. Wilkinson
Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans
Hypertension, October 1, 2006; 48(4): 602 - 608.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. Feletou and P. M. Vanhoutte
Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture)
Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002.
[Abstract] [Full Text] [PDF]


Home page
Vasc MedHome page
M. J Roman, T. Z Naqvi, J. M Gardin, M. Gerhard-Herman, M. Jaff, and E. Mohler
American Society of Echocardiography Report: Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology
Vascular Medicine, August 1, 2006; 11(3): 201 - 211.
[PDF]


Home page
HypertensionHome page
W.-Z. Zhang, K. Venardos, J. Chin-Dusting, and D. M. Kaye
Adverse Effects of Cigarette Smoke on NO Bioavailability: Role of Arginine Metabolism and Oxidative Stress
Hypertension, August 1, 2006; 48(2): 278 - 285.
[Abstract] [Full Text] [PDF]


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Eur J EndocrinolHome page
A Dagre, J Lekakis, C Mihas, A Protogerou, L Thalassinou, D Tryfonopoulos, G Douridas, C Papamichael, and M Alevizaki
Association of dehydroepiandrosterone-sulfate with endothelial function in young women with polycystic ovary syndrome.
Eur. J. Endocrinol., June 1, 2006; 154(6): 883 - 890.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
R. S. Vasan
Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations
Circulation, May 16, 2006; 113(19): 2335 - 2362.
[Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone
Uric Acid and Endothelial Dysfunction in Essential Hypertension
J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
A. A. Elesber, H. Solomon, R. J. Lennon, V. Mathew, A. Prasad, G. Pumper, R. E. Nelson, J. P. McConnell, L. O. Lerman, and A. Lerman
Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis
Eur. Heart J., April 1, 2006; 27(7): 824 - 831.
[Abstract] [Full Text] [PDF]


Home page
HeartHome page
D Tousoulis, M Charakida, and C Stefanadis
Endothelial function and inflammation in coronary artery disease
Heart, April 1, 2006; 92(4): 441 - 444.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
C. Zoccali
Endothelial Dysfunction and the Kidney: Emerging Risk Factors for Renal Insufficiency and Cardiovascular Outcomes in Essential Hypertension.
J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S61 - S63.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
U. Campia, L. A. Matuskey, and J. A. Panza
Peroxisome Proliferator-Activated Receptor-{gamma} Activation With Pioglitazone Improves Endothelium-Dependent Dilation in Nondiabetic Patients With Major Cardiovascular Risk Factors
Circulation, February 14, 2006; 113(6): 867 - 875.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
C. N. Bairey Merz, L. J. Shaw, S. E. Reis, V. Bittner, S. F. Kelsey, M. Olson, B. D. Johnson, C. J. Pepine, S. Mankad, B. L. Sharaf, et al.
Insights From the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: Gender Differences in Presentation, Diagnosis, and Outcome With Regard to Gender-Based Pathophysiology of Atherosclerosis and Macrovascular and Microvascular Coronary Disease
J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S21 - S29.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
M. L. Diez-Marques, M. P. Ruiz-Torres, M. Griera, S. Lopez-Ongil, M. Saura, D. Rodriguez-Puyol, and M. Rodriguez-Puyol
Arg-Gly-Asp (RGD)-containing peptides increase soluble guanylate cyclase in contractile cells
Cardiovasc Res, February 1, 2006; 69(2): 359 - 369.
[Abstract] [Full Text] [PDF]


Home page
Annals of Clinical & Laboratory ScienceHome page
M. Sahin, C. Arslan, M. Naziroglu, S. E. Tunc, M. Demirci, R. Sutcu, and N. Yilmaz
Asymmetric Dimethylarginine and Nitric Oxide Levels as Signs of Endothelial Dysfunction in Behcet's Disease
Ann. Clin. Lab. Sci., January 1, 2006; 36(4): 449 - 454.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
P. M. Thule, A. G. Campbell, D. J. Kleinhenz, D. E. Olson, J. J. Boutwell, R. L. Sutliff, and C. M. Hart
Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats
Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E114 - E122.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
J. J. Oliver, D. J. Webb, and D. E. Newby
Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans
Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2470 - 2479.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
H. Noda, H. Iso, H. Toyoshima, C. Date, A. Yamamoto, S. Kikuchi, A. Koizumi, T. Kondo, Y. Watanabe, Y. Wada, et al.
Walking and Sports Participation and Mortality From Coronary Heart Disease and Stroke
J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1761 - 1767.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
L. Lind, N. Fors, J. Hall, K. Marttala, and A. Stenborg
A Comparison of Three Different Methods to Evaluate Endothelium-Dependent Vasodilation in the Elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study
Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2368 - 2375.
[Abstract] [Full Text] [PDF]


Home page
J CARDIOVASC PHARMACOL THERHome page
G. Dell'Omo, G. Penno, S. Del Prato, and R. Pedrinelli
Chlorthalidone Improves Endothelial-Mediated Vascular Responses in Hypertension Complicated by Nondiabetic Metabolic Syndrome
Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 265 - 272.
[Abstract] [PDF]


Home page
HeartHome page
L C Jones and A D Hingorani
Genetic regulation of endothelial function
Heart, October 1, 2005; 91(10): 1275 - 1277.
[Full Text] [PDF]


Home page
HeartHome page
J A Vita
Endothelial function and clinical outcome
Heart, October 1, 2005; 91(10): 1278 - 1279.
[Full Text] [PDF]


Home page
HypertensionHome page
S. J. Duffy, E. S. Biegelsen, R. T. Eberhardt, D. F. Kahn, B. A. Kingwell, and J. A. Vita
Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation
Hypertension, October 1, 2005; 46(4): 707 - 713.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
B. Meyer, D. Mortl, K. Strecker, M. Hulsmann, V. Kulemann, T. Neunteufl, R. Pacher, and R. Berger
Flow-Mediated Vasodilation Predicts Outcome in Patients With Chronic Heart Failure: Comparison With B-Type Natriuretic Peptide
J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1011 - 1018.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
S. S. Najjar, A. Scuteri, and E. G. Lakatta
Arterial Aging: Is It an Immutable Cardiovascular Risk Factor?
Hypertension, September 1, 2005; 46(3): 454 - 462.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
E. Oechslin, W. Kiowski, R. Schindler, A. Bernheim, B. Julius, and H. P. Brunner-La Rocca
Systemic Endothelial Dysfunction in Adults With Cyanotic Congenital Heart Disease
Circulation, August 23, 2005; 112(8): 1106 - 1112.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
A. Sherwood, A. L. Hinderliter, L. L. Watkins, R. A. Waugh, and J. A. Blumenthal
Impaired Endothelial Function in Coronary Heart Disease Patients With Depressive Symptomatology
J. Am. Coll. Cardiol., August 16, 2005; 46(4): 656 - 659.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
Y. Neishi, S. Mochizuki, T. Miyasaka, T. Kawamoto, T. Kume, R. Sukmawan, M. Tsukiji, Y. Ogasawara, F. Kajiya, T. Akasaka, et al.
Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration
PNAS, August 9, 2005; 102(32): 11456 - 11461.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
F. Perticone, A. Sciacqua, R. Maio, M. Perticone, R. Maas, R. H. Boger, G. Tripepi, G. Sesti, and C. Zoccali
Asymmetric Dimethylarginine, L-Arginine, and Endothelial Dysfunction in Essential Hypertension
J. Am. Coll. Cardiol., August 2, 2005; 46(3): 518 - 523.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. A. Potenza, F. L. Marasciulo, D. M. Chieppa, G. S. Brigiani, G. Formoso, M. J. Quon, and M. Montagnani
Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production
Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H813 - H822.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
A. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints
Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool?
Chest, June 1, 2005; 127(6): 2254 - 2263.
[Abstract] [Full Text] [PDF]


Home page
HeartHome page
A D Gavin and A D Struthers
Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure
Heart, June 1, 2005; 91(6): 749 - 753.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
F. Mittermayer, G. Schaller, J. Pleiner, A. Vychytil, G. Sunder-Plassmann, W. H. Horl, and M. Wolzt
Asymmetrical Dimethylarginine Plasma Concentrations Are Related to Basal Nitric Oxide Release but Not Endothelium-Dependent Vasodilation of Resistance Arteries in Peritoneal Dialysis Patients
J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1832 - 1838.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
A. Sciacqua, A. Scozzafava, A. Pujia, R. Maio, F. Borrello, F. Andreozzi, M. Vatrano, S. Cassano, M. Perticone, G. Sesti, et al.
Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension
Eur. Heart J., May 1, 2005; 26(9): 921 - 927.
[Abstract] [Full Text] [PDF]


Home page
JAMAHome page
J. A. Blumenthal, A. Sherwood, M. A. Babyak, L. L. Watkins, R. Waugh, A. Georgiades, S. L. Bacon, J. Hayano, R. E. Coleman, and A. Hinderliter
Effects of Exercise and Stress Management Training on Markers of Cardiovascular Risk in Patients With Ischemic Heart Disease: A Randomized Controlled Trial
JAMA, April 6, 2005; 293(13): 1626 - 1634.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
J. Passauer, F. Pistrosch, E. Bussemaker, G. Lassig, K. Herbrig, and P. Gross
Reduced Agonist-Induced Endothelium-Dependent Vasodilation in Uremia Is Attributable to an Impairment of Vascular Nitric Oxide
J. Am. Soc. Nephrol., April 1, 2005; 16(4): 959 - 965.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
A. Natali, E. Toschi, S. Baldeweg, A. Casolaro, S. Baldi, A. M. Sironi, J. S. Yudkin, and E. Ferrannini
Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels
Eur. Heart J., March 1, 2005; 26(5): 464 - 471.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
R. K. Kharbanda, S. Wallace, B. Walton, A. Donald, J. M. Cross, and J. Deanfield
Systemic Acyl-CoA:Cholesterol Acyltransferase Inhibition Reduces Inflammation and Improves Vascular Function in Hypercholesterolemia
Circulation, February 15, 2005; 111(6): 804 - 807.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
J. A Vita
Polyphenols and cardiovascular disease: effects on endothelial and platelet function
Am. J. Clinical Nutrition, January 1, 2005; 81(1): 292S - 297S.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
D. Fischer, S. Rossa, U. Landmesser, S. Spiekermann, N. Engberding, B. Hornig, and H. Drexler
Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death
Eur. Heart J., January 1, 2005; 26(1): 65 - 69.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
U. Ghani, A. Shuaib, A. Salam, A. Nasir, U. Shuaib, T. Jeerakathil, F. Sher, F. O'Rourke, A. M. Nasser, B. Schwindt, et al.
Endothelial Progenitor Cells During Cerebrovascular Disease
Stroke, January 1, 2005; 36(1): 151 - 153.
[Abstract] [Full Text] [PDF]


Home page
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Impact of the type of dialyser on the clinical outcome in chronic haemodialysis patients: does it really matter?
Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2965 - 2970.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
F. Wiesmann, S. E. Petersen, P. M. Leeson, J. M. Francis, M. D. Robson, Q. Wang, R. Choudhury, K. M. Channon, and S. Neubauer
Global impairment of brachial, carotid, and aortic vascular function in young smokers: Direct quantification by high-resolution magnetic resonance imaging
J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2056 - 2064.
[Abstract] [Full Text] [PDF]


Home page
J. Physiol.Home page
D. J Green, A. Maiorana, G. O'Driscoll, and R. Taylor
Effect of exercise training on endothelium-derived nitric oxide function in humans
J. Physiol., November 15, 2004; 561(1): 1 - 25.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
S. Fazel, R. D. Weisel, and S. Verma
A novel technique to assess flow-mediated vasodilation
J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1478 - 1480.
[Full Text] [PDF]


Home page
CirculationHome page
S. Fichtlscherer, S. Breuer, and A. M. Zeiher
Prognostic Value of Systemic Endothelial Dysfunction in Patients With Acute Coronary Syndromes: Further Evidence for the Existence of the "Vulnerable" Patient
Circulation, October 5, 2004; 110(14): 1926 - 1932.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
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Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes
Nephrol. Dial. Transplant., October 1, 2004; 19(10): 2513 - 2518.
[Abstract] [Full Text] [PDF]


Home page
J. Nutr.Home page
N. Gokce
L-Arginine and Hypertension
J. Nutr., October 1, 2004; 134(10): 2807S - 2811S.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
T. Suvorava, N. Lauer, and G. Kojda
Physical inactivity causes endothelial dysfunction in healthy young mice
J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1320 - 1327.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
F. Perticone, R. Maio, G. Tripepi, and C. Zoccali
Endothelial Dysfunction and Mild Renal Insufficiency in Essential Hypertension
Circulation, August 17, 2004; 110(7): 821 - 825.
[Abstract] [Full Text] [PDF]


Home page
LupusHome page
S R Johnson, P J Harvey, J S Floras, M Iwanochko, D Ibanez, D D Gladman, and M Urowitz
Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations
Lupus, August 1, 2004; 13(8): 590 - 593.
[Abstract] [PDF]


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