1、Ventricular20HypertrophyHypertension. 1997;29:706-714.)Effect of African-American Race and Hypertensive Left Ventricular Hypertrophy on Coronary Vascular Reactivity and Endothelial Function Jan L. Houghton; Vivienne E. Smith; David S. Strogatz; Nancy L. Henches; Warren M. Breisblatt; Albert A. Carr
2、the Division of Cardiology, Department of Medicine, Albany (NY) Medical College (J.L.H., V.E.S., N.L.H., W.M.B.); School of Public Health, State University of New York at Albany (D.S.S.); and Augusta (Ga) Preventive Cardiology, PC (A.A.C.). AbstractExcess cardiovascular morbidity and mortality among
3、 African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we s
4、ubjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase i
5、n coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorica
6、l and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertroph
7、y. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and d
8、ilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxatio
9、n during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy. Key Words: blacks race vasorelaxation hypertrophy, left ventricular vascular reactivity endothelial function IntroductionExc
10、ess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem.1 2 Furthermore, the paradoxical finding of a lesser degree of coronary atherosclerosis but worse prognosis after diagnosis of ischemic heart disease exists among bla
11、ck Americans.3 4 Although myocardial ischemia is generally secondary to coronary artery atherosclerosis, the demonstration of ischemia with normal coronary arteries (syndrome X, aortic stenosis, left ventricular hypertrophy LVH) has clarified the concepts of microvascular angina and nonatherosclerot
12、ic supply/demand mismatch.5 6 7 8 9 These concepts, together with an evolving understanding of the endothelium, justify investigations that emphasize the central importance of the coronary microcirculation and endothelium in the regulation of myocardial perfusion.10 11 A number of possible explanati
13、ons have been advanced to address the perceived paradox of greater myocardial ischemia despite less atherosclerotic disease among blacks. One invokes societal-based factors related to socioeconomic status, such as access to medical care, compliance issues, and the duration of untreated or poorly tre
14、ated cardiovascular disease.12 13 14 A second explanation proposes that comorbid diseases or processes more prevalent in black Americans, such as hypertension and diabetes mellitus, may augment ischemia by affecting supply and demand through mechanisms other than atherosclerosis.6 15 16 17 Third, in
15、trinsic abnormalities in the coronary endothelium and microcirculation may be present in black Americans, possibly as part of a generalized defect in vascular relaxation, thus leading to abnormal perfusion of the myocardium in the absence of atherosclerosis.18 19 Our purpose in this study was to exa
16、mine the effects of hypertensive LVH and race on coronary artery and arteriolar vasorelaxation in response to the endothelium-dependent agent acetylcholine and the predominantly endothelium-independent agent adenosine in a cohort of black and white Americans with angiographically normal coronary art
17、eries. Comparisons were made among normotensive subjects and subjects with complicated hypertension, defined as hypertension plus LVH. Study subjects were identified for possible participation after clinical referral for cardiac catheterization because of suspected ischemic heart disease. MethodsSub
18、jectsSubjects were prospectively recruited for the approved investigational study (Albany Medical College Institutional Review Board) after clinical referral for cardiac catheterization for evaluation of chest pain. Informed consent was obtained, which documented the participants understanding of th
19、e investigational nature of the protocol. The current study is part of a larger study whose purpose is examination of the effects of hypertension, LVH, hemodynamically insignificant atherosclerosis, sex, and ethnicity on coronary artery and arteriolar relaxation. Enrolled subjects had normal epicard
20、ial coronary arteries documented during coronary angiography. Individuals were excluded from the study if they had a history of myocardial infarction, balloon angioplasty, bypass surgery, significant valvular heart disease, or other serious medical disorder. Subjects fasted for a minimum of 8 hours
21、before the study. Current smokers were instructed to refrain from smoking for a minimum of 8 hours. Subjects were grouped by race and presence of hypertensive LVH. Hypertension was defined as reproducible blood pressure measurements greater than or equal to 140/90 mm Hg or self-reported taking of an
22、tihypertensive medication. Diabetes mellitus was diagnosed by self-reported history or fasting serum glucose greater than 7.8 mmol/L (140 mg/dL). All subjects were referred for cardiac catheterization for evaluation of chest pain or an angina equivalent. Chest pain was classified as angina pectoris,
23、 atypical angina, or noncardiac chest pain. Angina pectoris was defined in the classic manner as substernal chest discomfort (heaviness or pressure) brought on by exertion and relieved by rest or nitroglycerin or a prolonged episode of anginal pain at rest requiring hospitalization. Atypical angina
24、was defined as chest pain with some features of classic angina but other characteristics not generally associated with angina pectoris, such as a sharp or pleuritic character or intermittent relationship to exercise. Noncardiac chest pain had no features of angina other than a substernal location of
25、 chest pain. An angina equivalent was defined as symptoms or findings commonly associated with ischemia in the absence of chest pain, such as dyspnea or heart failure. In normotensive subjects, 6 black (60%) and 13 white (62%) were judged to have angina pectoris; 2 black (20%) and 7 white (33%), aty
26、pical angina; 2 black (20%) and 0 white, an anginal equivalent; and 0 black and 1 white (5%), noncardiac chest pain. In hypertensive subjects with LVH, 13 black (52%) and 11 white (46%) were judged to have angina pectoris; 5 black (20%) and 9 white (38%), atypical angina; 6 black (24%) and 2 white (
27、8%), an anginal equivalent; and 1 black (4%) and 2 white (8%), noncardiac chest pain. Twenty-nine of 45 white subjects (64%) and 24 of 35 black subjects (69%) were taking medications for chest pain and/or hypertension. Seventeen of these 29 white subjects (59%) and 12 of these 24 black subjects (50%
28、) were taking drugs expected to have coronary vasodilating properties alone (nitroglycerin and/or calcium channel blockers). Two white (7%) and 1 black (4%) subjects were taking a -blocker alone. However, 5 white (17%) and 6 black (25%) subjects were taking both a -blocker and coronary vasodilator.
29、Finally, the remaining 5 white (17%) and 5 black (21%) subjects were taking an angiotensin-converting enzyme inhibitor or -blocker together with other drugs. Eight white (28%) and 9 black (38%) subjects used diuretics in addition to the medications already described. Whenever possible, vasoactive an
30、d antihypertensive medications were withheld for a minimum of 12 hours before the study although the study design permitted sublingual nitroglycerin if deemed clinically necessary; however, no subject required sublingual nitroglycerin within 4 hours. In 10 of 80 study subjects (5 white and 5 black),
31、 medications with vasoactive potential were used within 12 hours because of clinical indication. Medications used within 12 hours were as follows: calcium channel blockers in 2 white subjects, nitroglycerin preparations in 2 white and 2 black subjects, a short-acting angiotensin-converting enzyme in
32、hibitor in 1 white subject, and 2 or more drugs in 3 black subjects. There were no significant racial differences in drug usage. Socioeconomic status was assessed by three indicators: years of formal education, possession of private medical insurance, and current employment status. Body mass index w
33、as calculated as weight (in kilograms) divided by height (in meters) squared. Blood was obtained with subjects in the fasting state for measurement of total cholesterol, low-density and high-density lipoprotein cholesterols, lipoprotein(a), and glucose. Left Ventricular Mass MeasurementsLeft ventricular (LV) mass was calculated with M-
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