Kathleen A. Sliney

Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude.

BACKGROUND Abnormalities in pulse wave amplitude (PWA) have been described in subjects with atherosclerosis and may be a marker of future cardiac events. We evaluated the relationship between changes in PWA of the finger and peripheral endothelial function. METHODS We performed measurements of PWA with a novel finger plethysmograph (peripheral arterial tonometry [PAT]) and compared the findings with a simultaneous noninvasive measurement of peripheral endothelial function with brachial artery ultrasound scanning (BAUS) in 89 subjects. The PAT hyperemia ratio was defined as the ratio of PWA during reactive hyperemia relative to the baseline. Flow-mediated dilation (FMD) was defined by BAUS as the ratio of the brachial artery diameter during reactive hyperemia relative to the baseline. Sixty-eight subjects underwent exercise myocardial perfusion imaging (ExMPI). RESULTS Fifty-four men and 35 women were examined. There was a linear relationship between the PAT hyperemia ratio and FMD during the same episode of reactive hyperemia (r = 0.55, P <.0001). Subjects in the lowest FMD quartile had the lowest PAT hyperemia ratio, whereas subjects in the highest FMD quartile had the highest PAT hyperemia ratio (P <.001 for trend). Similar to BAUS, the PAT hyperemia ratio was more impaired in subjects with cardiovascular risk factors and in subjects with ExMPI studies that were indicative of coronary artery disease. CONCLUSIONS Assessment of PWA with PAT demonstrates patterns of abnormality similar to that of BAUS assessment of FMD. PWA during reactive hyperemia is influenced by factors known to affect endothelial function, including cardiovascular risk factors and coronary artery disease. These findings support the concept that analysis of PWA with PAT during reactive hyperemia may be used to study peripheral vascular endothelial function.

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease

OBJECTIVES We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.

Pulse pressure and peripheral arterial vasoreactivity

Elevated pulse pressure is a predictor of coronary artery disease. Endothelial dysfunction, due to the loss of normal regulation of vascular tone, is also prevalent in patients with cardiovascular risk factors and/or atherosclerosis, and its presence has prognostic importance. Endothelial dysfunction is implicated in the pathophysiology of essential hypertension and is likely partially responsible for abnormalities in vascular resistance and structure. In this study, we sought to further evaluate the relationship between pulse pressure and peripheral vascular endothelial function in subjects undergoing evaluation for the presence of atherosclerosis. Subjects undergoing clinically indicated exercise stress testing (Bruce Protocol) were recruited. Exclusion criteria included myocardial infarction/ unstable angina within the previous 3 months, congestive heart failure, or valvular heart disease. The presence of coronary artery disease was defined by myocardial perfusion abnormalities on nuclear perfusion scans. Brachial artery systolic and diastolic blood pressures were evaluated in the supine position and pulse pressure was calculated as the difference between systolic blood pressure and diastolic blood pressure (mmHg). Evaluation of peripheral vascular endothelial function and blood pressure was performed in the morning hours in a fasting state and cardiovascular medications were held for 12 h prior to testing. Longitudinal images of the brachial artery were obtained with a high-resolution (10 MHz) linear array vascular transducer (General Electric, Vingmed, System Five, Horten, Norway) before and after a 5-min ischemic period induced by upper-arm occlusion with a pressure cuff. After exactly 1 min of reactive hyperaemia, the brachial artery dimension was obtained and compared to the baseline image. Baseline brachial artery dimensions were obtained 10 min later and compared with those 5 min following administration of sublingual nitroglycerin (400 mg). Maximal end-diastolic brachial arterial diameters were calculated within a 5-cm segment of the vessel as the mean of evenly spaced measurements of the distance between the two walls of the artery along a line perpendicular to the long axis of the artery. Endothelium-dependent vasomotion, defined as per cent flow-mediated dilation (FMD), was calculated as the difference between the maximal brachial artery diameter during reactive hyperaemia and the baseline brachial diameter divided by the baseline brachial artery diameter. Endothelium-independent vasomotion was defined as per cent nitroglycerinmediated dilation (NMD) and calculated as the difference between the maximal brachial artery diameter following nitroglycerin administration and the baseline brachial artery diameter divided by the baseline brachial artery diameter. Data are expressed as mean7standard deviation. Univariate analysis (t-test) was employed to assess statistical significance between groups. A receiver– operator curve was analysed to establish a cut-point of 10% for FMD, providing the maximum sensitivity (91%) with the least effect on specificity for identification of coronary artery disease. In all analyses, a P-value o0.05 was considered statistically significant. A total of 87 subjects were enrolled (48 men, 39 women) with an average age of 56711 years. In total, 47% had hypertension, 43% hypercholesterolaemia, and 9% diabetes mellitus. The average FMD was 9.775.0% and the average NMD was 1877.7%. The mean systolic and diastolic pressures were 130718 and 79710 mmHg, respectively, and the average pulse pressure was 51716 mmHg. The 47 subjects with endothelial dysfunction (FMD o10%) had a higher pulse pressure (55717 mmHg) compared with the 40 subjects with preserved endothelial function (FMD X10%; 47713 mmHg; P1⁄4 0.02). The increase in pulse pressure in this group was primarily due to higher systolic blood pressure (134717 mmHg), which was significantly higher than in patients with FMD 410% (126718 mmHg; P1⁄4 0.02). There were no differences in diastolic blood pressure between patients with high or low FMD. Pulse pressure was significantly higher (62722 mmHg) in the 12 subjects with coronary artery disease compared with the 75 subjects without coronary artery disease (50714 mmHg; P1⁄4 0.01) (Table 1). As expected, FMD was lower in those with coronary artery disease (6.172.5%) compared with those without coronary artery disease (10.375.0%; Journal of Human Hypertension (2005) 19, 501–502 & 2005 Nature Publishing Group All rights reserved 0950-9240/05

Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease.

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