Association of cardiovascular risk factors with microvascular and conduit artery function in hypertensive subjects.

BACKGROUND Alterations in microvascular and conduit artery function contribute to target organ damage in hypertension. We investigated the association of cardiovascular (CV) risk factors with microvascular and conduit artery function in hypertensive subjects. METHODS Participants included 504 hypertensives (aged 62.1 +/- 9.8 years, 42% men) from the community, without history of symptomatic CV disease. Brachial artery ultrasound was performed to measure forearm blood flow (FBF) at rest and during reactive hyperemia (markers of microvascular function) and flow-mediated dilatation (FMD) of the brachial artery (a marker of conduit artery endothelial function). The association of conventional and novel (homocysteine, C-reactive protein, fibrinogen, and lipoprotein a CV risk factors with microvascular function and FMD was tested in multivariable regression models. RESULTS Variables independently associated with higher resting FBF were male sex, higher body mass index (BMI), smoking, and lower HDL-cholesterol; variables associated with lower hyperemic FBF included greater age, female sex, and diabetes. Higher plasma homocysteine was associated with lower hyperemic FBF in obese subjects (P for log homocysteine x BMI interaction = .0008). Variables independently associated with lower FMD were greater age, sex gender, history of smoking, and not using statins. Higher homocysteine was associated with lower FMD in subjects with higher systolic blood pressure (P for interaction = .0004). Hyperemic flow velocity was independently associated with FMD (P = .0006), but its inclusion as a covariate did not influence the association of CV risk factors with FMD. CONCLUSIONS In asymptomatic subjects with essential hypertension, select CV risk factors were associated with microvascular and conduit artery function. Furthermore, the association of CV risk factors with conduit artery function appeared to be independent of downstream microvascular function.

[1]  T. Ogihara,et al.  Impaired endothelial function with essential hypertension assessed by ultrasonography. , 1996, American heart journal.

[2]  M. Lefevre,et al.  Influence of age and normal plasma fibrinogen levels on flow-mediated dilation in healthy adults. , 2000, The American journal of cardiology.

[3]  E. Lonn,et al.  Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men. , 2005, Journal of the American College of Cardiology.

[4]  D. Celermajer,et al.  Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. , 1994, Journal of the American College of Cardiology.

[5]  C. Stehouwer,et al.  Plasma homocysteine is weakly correlated with plasma endothelin and von Willebrand factor but not with endothelium-dependent vasodilatation in healthy postmenopausal women. , 1999, Clinical chemistry.

[6]  J. Brophy,et al.  Absence of Association Between Infectious Agents and Endothelial Function in Healthy Young Men , 2003, Circulation.

[7]  L. Bielak,et al.  Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults. , 2007, Clinical science.

[8]  K. Woo,et al.  Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. , 1997, Circulation.

[9]  D. Levy,et al.  Local Shear Stress and Brachial Artery Flow–Mediated Dilation: The Framingham Heart Study , 2004, Hypertension.

[10]  E. Boerwinkle,et al.  Lack of association between lipoprotein(a) and coronary artery calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. , 2004, Mayo Clinic proceedings.

[11]  M. Sugimachi,et al.  Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P. , 1995, Hypertension.

[12]  S. Fichtlscherer,et al.  Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease , 2000, Circulation.

[13]  R. Schmieder,et al.  Does lipoprotein(a) impair endothelial function? , 1998, Journal of the American College of Cardiology.

[14]  E. Lonn,et al.  Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals. , 2004, European heart journal.

[15]  S. Homma,et al.  High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort. , 2004, Journal of the American College of Cardiology.

[16]  B. Strauer,et al.  Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension , 2005, Journal of hypertension.

[17]  B. Casetta,et al.  Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electrospray tandem mass spectrometry. , 1999, Clinical chemistry.

[18]  E. Benjamin,et al.  Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study , 2004, Circulation.

[19]  G. McVeigh,et al.  Microcirculatory Hemodynamics and Endothelial Dysfunction in Systemic Lupus Erythematosus , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[20]  E. Ernst,et al.  Fibrinogen as a Cardiovascular Risk Factor , 1993, Annals of Internal Medicine.

[21]  A. Pries,et al.  Microcirculation in Hypertension: A New Target for Treatment? , 2001, Circulation.

[22]  B. Keevil,et al.  Evaluation of a Latex-Enhanced Immunoturbidimetric Assay for Measuring Low Concentrations of C-Reactive Protein , 1998, Annals of clinical biochemistry.

[23]  G. Kajiyama,et al.  A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. , 2000, Journal of the American College of Cardiology.

[24]  A. Clauss,et al.  Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens , 1957 .

[25]  P. Ganz,et al.  Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide. , 1996, The American journal of physiology.

[26]  C. Mogensen,et al.  The Stages in Diabetic Renal Disease: With Emphasis on the Stage of Incipient Diabetic Nephropathy , 1983, Diabetes.

[27]  G. Moneta,et al.  Homocysteine and arterial disease. Experimental mechanisms. , 2002, Vascular pharmacology.

[28]  K Y Liang,et al.  Longitudinal data analysis for discrete and continuous outcomes. , 1986, Biometrics.

[29]  J. Loscalzo,et al.  Ischemia, hyperemia, exercise, and nitric oxide. Complex physiology and complex molecular adaptations. , 1994, Circulation.

[30]  W E Haefeli,et al.  Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. , 1995, Circulation.

[31]  E. Benjamin,et al.  Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study , 2004, Circulation.