Biomedical subjects

Barry L Sharaf

Publications and source records attributed to Barry L Sharaf.

24 records · Page 2Linked to original sources

PubMed2003

APOE polymorphism and angiographic coronary artery disease severity in the Women's Ischemia Syndrome Evaluation (WISE) study.

Genetic variation in the apolipoprotein E (APOE) gene is a significant determinant of variation in plasma cholesterol levels and it also affects the risk of coronary artery disease (CAD). We examined the association of the APOE polymorphism with CAD severity in women from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Quantitative coronary angiography was used to classify subjects as having normal/minimal CAD (<20% stenosis), mild CAD (20-49% stenosis) and significant CAD (>or=50% stenosis). The women with or=50% stenosis were further stratified according to the number of vessel disease they have (one, two, or three). In white subjects, the frequency of APOE*4 carriers (3/4 and 4/4 genotypes) was significantly higher in the combined mild/significant CAD group (>or=20% stenosis) compared with the normal/minimal CAD group (<20% stenosis) (31.3 vs. 19.2%; P=0.025) with an adjusted OR of 2.40 (95% CI: 1.47-3.93; P=0.0005). Furthermore, the APOE*4 allele was found to be significantly associated with the increased vessel disease number (chi(2)=8.04; P=0.0046). This association of the APOE*4 allele with CAD severity was present only in women with family history of CAD. APOE polymorphism also showed significant associations with increasing plasma total cholesterol (P=0.01) and low-density lipoprotein (LDL)-cholesterol (P<0.001) in whites. These data support the hypothesis that the APOE*4 allele is an independent risk factor not only for the presence of CAD and hyperlipidemia, but also for the angiographic severity of CAD in white women with a family history of disease.

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PubMed2003

Symptoms, myocardial ischaemia and quality of life in women: results from the NHLBI-sponsored WISE Study.

AIMS: Our goal was to evaluate health-related quality of life (QOL) in women undergoing angiography for suspected ischaemia. METHODS AND RESULTS: QOL measurements were obtained in 406 women with chest pain symptoms in the Women's Ischemia Syndrome Evaluation (WISE). QOL measures included a general rating (GR), Duke Activity Status Index (DASI), and the Beck Depression Inventory (BDI). Higher scores on the GR and DASI are indicative of better QOL and functioning. Higher scores on the BDI indicate more symptoms of depression. Women were stratified by the presence and absence of obstructive angiographic coronary artery disease (CAD) and by the presence and absence of myocardial ischaemia. Women with angiographic obstructive CAD had lower DASI and higher BDI scores compared to women without obstructive CAD (both P<0.05). Stratification by the presence and absence of ischaemia demonstrated that women with ischaemia had better QOL, evidenced by higher GR QOL scores and lower BDI scores (both P<0.05) than women without ischaemia. Symptoms of angina were significant independent predictors of QOL scores (P<0.001). CONCLUSIONS: Chest pain symptoms have a significant impact on health-related QOL in women undergoing coronary angiography for suspected myocardial ischaemia andare more important determinants of QOL than the underlying conditions of CAD or ischaemia.

Activities of Daily Living↗

PubMed2002

Association between the severity of angiographic coronary artery disease and paraoxonase gene polymorphisms in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

Paraoxonase (PON), a high-density lipoprotein-associated enzyme, is believed to protect against low-density lipoprotein oxidation and thus affects the risk of coronary artery disease (CAD). Three polymorphisms in the PON1 (Leu55Met and Gln192Arg) and PON2 (Ser311Cys) genes have been shown to be associated with the risk of CAD in several European or European-derived populations. In the present study, we examined the associations between these three markers and the severity of CAD as determined by the number of diseased coronary artery vessels in 711 subjects (589 whites and 122 blacks) from the Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a National Heart, Lung, and Blood Institute-sponsored multicenter study designed to address issues related to ischemic-heart-disease recognition and diagnosis in women. Subjects were classified as having normal/minimal CAD (<20% stenosis), mild CAD (20%-49% stenosis), and significant CAD (>/=50% stenosis). The women who had >/=50% stenosis were further classified into groups with one-, two-, or three-vessel disease if any of the three coronary arteries had diameter stenosis >/=50%. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON1 codon 192 Arg/Arg genotype was significantly higher in the group with three-vessel disease than in the other groups (those with one-vessel and two-vessel disease) combined (17.02% vs. 4.58%; P=.0066). Similarly, the frequency of the PON2 codon 311 Cys/Cys genotype was significantly higher in the group with three-vessel disease than in the other groups combined (15.22% vs. 4.61%; P=.018). The adjusted odds ratios for the development of three-vessel disease were 2.80 (95% confidence interval 1.06-7.37; P=.038) for PON1 codon 192 Arg/Arg and 3.68 (95% confidence interval 1.26-10.68; P=.017) for PON2 codon 311 Cys/Cys. Our data indicate that the severity of CAD, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster, on chromosome 7.

Adult↗

PubMed2002

Mild renal insufficiency is associated with angiographic coronary artery disease in women.

BACKGROUND: Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results- Women with chest pain who were referred for coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (r=0.11, P<0.004) and maximum coronary artery stenosis (r=0.11, P<0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (>/=50% diameter stenosis in >/=1 coronary artery) (61% versus 37%; P<0.001) and CAD in multiple vessels (P<0.001 for association) and had greater maximum percent diameter coronary stenosis (59+/-35% versus 38+/-36%; P<0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2). CONCLUSIONS: In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.

Biomarkers↗

PubMed2002

Electrocardiogram abnormalities predict angiographic coronary artery disease in women with chest pain: results from the NHLBI WISE Study.

BACKGROUND AND HYPOTHESIS: Noninvasive risk stratification for coronary artery disease (CAD) isless accurate in women than in men. Based on recent reports that gender-specific exercise electrocardiogram (ECG) parameters predict CAD, we evaluated the independent predictive value of the resting ECG for angiographic CAD in women with chest pain. METHODS: Women (n = 850, mean age 58 years) with chest pain in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) underwent 12-lead ECG testing and quantitative coronary angiography. RESULTS: Significant angiographic CAD (> or = 50% stenosis in > or = 1 coronary) was present in 39% of women. Q waves in < or = 2 contiguous ECG leads were present in 107 women (13%), including 49 of 657 (7%) without history of infarction. Among 585 women without prior infarction orrevascularization, 48% of those with Q waves in contiguous leads versus 26% of others, had significant CAD (p = 0.003; odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.3-4.8). Women with Q waves in < or = 2 inferior ECG leads were particularly likely to have CAD (63 vs. 26% of others, p < 0.001; OR = 4.6,95% CI = 2.0-10.8). Other ECG findings predictive of CAD were any ST-T abnormality (OR = 1.9,95% CI = 1.3-2.8) and T-wave inversion (OR = 2.4, 95% CI = 1.3-4.2). In risk-adjusted analysis, inferior Q waves and T-wave inversion independently predicted significant CAD. When considered together with radionuclide perfusion test results, T-wave inversion on resting ECG added significant independent predictive value (OR = 2.8, 95% CI = 1.1-7.2, p = 0.03). CONCLUSIONS: Selected resting ECG parameters independently predict angiographic CAD in women with chest pain, including women who have also undergone radionuclide stress testing. Prospective studies should consider resting ECG parameters in diagnostic algorithms for CAD in women.

Algorithms↗

PubMed2002

Large brachial artery diameter is associated with angiographic coronary artery disease in women.

BACKGROUND: Noninvasive methods are needed for the identification of women at highest risk for coronary artery disease (CAD) who might benefit most from aggressive preventive therapy. Identification of brachial artery atherosclerosis, which correlates with coronary artery atherosclerosis, may be useful to estimate or stratify CAD risk. Because atherosclerosis disrupts the arterial architecture that regulates vessel size, we hypothesized that noninvasively measured large brachial artery diameter is a manifestation of atherosclerosis that is associated with angiographic CAD in women with chest pain. METHODS: We examined 376 women (mean age, 57.1 years) with chest pain in the National Heart, Lung, and Blood Institute's Women's Ischemia Syndrome Evaluation study who underwent B-mode ultrasound scan measurement of brachial artery diameter at rest and during hyperemic stress (to quantify flow-mediated dilation), quantitative coronary angiography, and risk factor assessment. RESULTS: Large resting brachial artery diameter was associated with significant angiographic CAD (3.90 +/- 0.79 mm vs 3.52 +/- 0.59 mm in women with CAD vs no CAD; P <.001). Impaired flow-mediated dilation, which correlated with resting diameter (r = -0.17; P =.001), was weakly associated with significant CAD (2.74% +/- 7.11% vs 4.48% +/- 9.52% in CAD vs no CAD; P =.046). After adjustment for age, body size, and CAD risk factors, women with large resting brachial artery diameters (>4.1 mm) had 3.6-fold increased odds (95% confidence interval, 1.8 to 7.1; P <.001) of significant angiographic CAD compared with those with small brachial arteries (</=3.6 mm). CONCLUSION: Large resting brachial artery diameter is an independent predictor of significant CAD in women with chest pain. Therefore, a simple ultrasonographic technique may be useful in the identification of women with chest pain who are at increased risk for CAD.

Adult↗