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Biomedical subjects

Cairistine Grahame-Clarke

Publications and source records attributed to Cairistine Grahame-Clarke.

9 recordsLinked to original sources

The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort.

BACKGROUND: Brachial artery flow-mediated dilation (FMD) may predict cardiovascular events in selected high-risk patients. Whether FMD testing predicts cardiovascular events in asymptomatic, lower risk individuals from the general population is unknown. METHODS AND RESULTS: As a part of a multi-ethnic, prospective cohort study, the Northern Manhattan Study, we examined FMD by high-resolution ultrasonography in 842 community participants who were free of stroke or myocardial infarction. Lower FMD levels predicted cardiovascular events (myocardial infarction, stroke and vascular death) at 36 months of follow-up (hazard ratio (HR)=1.12 for every 1% decrease in FMD, 95% CI 1.01-1.25, p=0.03). The risk of events in patients with FMD in the lower two tertiles (FMD<7.5%) was significantly higher than those in the highest tertile (HR=3.28, 95% CI 1.07-10.06, p=0.04 for lowest versus highest tertile, and HR=3.05, 95% CI 1.03-9.66, p=0.04 for middle versus highest tertile). In a multivariate analysis including cardiovascular risk factors, the increase in risk associated with FMD was no longer statistically significant. CONCLUSIONS: Non-invasive FMD testing predicts incident cardiovascular events in this multi-ethnic, population-based sample, but its predictive value is not independent of cardiovascular risk factors.

Aged↗

Aortic valve calcification as an incidental finding at CT of the elderly: severity and location as predictors of aortic stenosis.

OBJECTIVE: The purpose of this study was to correlate the severity and location of aortic valve calcifications, as an incidental finding at chest CT of elderly persons, with pressure gradients across the valve. MATERIALS AND METHODS: One hundred fifteen subjects who were 60 years old or older and who showed aortic valve calcification on chest CT (5-mm reconstructed section width, no IV contrast material) and who had also undergone transthoracic echocardiography within 3 months of the CT examination were identified retrospectively. Aortic valve calcification scores (Agatston and volumetric) and subjective calcification pattern scores (based on a 9-point scale) were calculated and correlated with echocardiographic gradients. RESULTS: Thirty patients (26%) (median age, 81 years) were identified who showed an increased pressure gradient across the aortic valve at echocardiography. Eighty-five subjects (74%), including 30 age-matched but otherwise randomly selected control subjects, showed no increase in pressure gradient. The severity of aortic valve calcification was greater for the 30 subjects with an increased gradient than for the control subjects (p < 0.0001). Increased mean and peak gradients across the aortic valve correlated with the subjective scores for aortic valve calcification (r = 0.69 and 0.65, respectively; p < 0.0001), with Agatston scores (r = 0.76 and 0.70, respectively; p < 0.0001), and with volumetric scores (r = 0.78 and 0.73, respectively; p < 0.0001). In terms of specific commissures, the greatest correlation with mean and peak gradients was for peripheral left-posterior commissural calcification (r = 0.71 and 0.65, respectively; p < 0.0001) and central right-left commissural calcification (r = 0.69 and 0.66, respectively; p < 0.0001). CONCLUSION: The severity of aortic valve calcifications on chest CT, as assessed either subjectively or objectively, correlated with increased pressure gradients across the aortic valve, particularly for calcification of the peripheral left-posterior commissure and the central right-left commissure. These results indicate that the severity and location of aortic valve calcifications on chest CT are associated with an increased pressure gradient across the aortic valve.

Aged↗

Association of increased body mass index and impaired endothelial function among Hispanic women.

We tested the hypothesis that an increased body mass index was similarly associated with impaired endothelial function as measured by flow-mediated dilation in a high-risk, Hispanic population of men and women living in northern Manhattan. The association of flow-mediated dilation and body mass index was significant in women (beta -0.16 +/- 0.04, p <0.0001) but not in men (beta -0.02 +/- 0.06, p = 0.72). This is the first study to demonstrate a gender-specific difference in endothelial function associated with body mass index.

Age Factors↗

Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus.

To determine whether endothelial dysfunction precedes the clinical diagnosis of diabetes mellitus, we investigated the relation of endothelial flow-mediated dilation (FMD) with fasting plasma glucose among a multiethnic population-based cohort of 579 nondiabetic subjects without previous myocardial infarction or stroke enrolled in the Northern Manhattan Study (age 66 +/- 9 years; 41% men, 16% white, 15% black, and 68% Hispanic). Impaired fasting glucose or prediabetic status, defined as a fasting glucose level of 100 to 125 mg/dl, was present in 95 subjects (16%). Endothelial function was determined using FMD during reactive hyperemia. Multiple linear regression analyses were used to assess the relation between plasma glucose and endothelial function after adjustment for potential confounders. FMD was significantly lower (4.9 +/- 3.8% vs 6.1 +/- 3.7%, p = 0.003) in those with impaired fasting glucose than in subjects with normal fasting glucose. Prediabetic status was significantly associated with impaired FMD (odds ratio 1.9, 95% confidence interval 1.1 to 3.1, p = 0.02). After adjustment for age, gender, body mass index, and hypertensive status, a higher fasting glucose was significantly associated with a lower FMD (beta = -0.024 +/- 0.012, p = 0.04) in a continuous linear relation. Thus, for each 10-mg/dl increase in plasma glucose, a 0.24% decrease occurred in FMD. Impaired FMD was present among prediabetics. An elevated fasting plasma glucose level is associated with impaired endothelial function among nondiabetics. These results further support the role of hyperglycemia in the pathogenesis of vascular dysfunction at different stages of diabetes development and the role of impaired fasting glucose as a risk factor for macrovascular disease.

Black or African American↗

Human cytomegalovirus, endothelial function and atherosclerosis.

Human cytomegalovirus (HCMV) serology is linked to several measures of endothelial dysfunction. There is substantial evidence for HCMV having an aetiological role in transplant arterial disease and accumulating evidence for HCMV in the origins of preeclampsia. However, whether HCMV is a clinically significant cause of atherosclerosis in the general, immunocompetent population remains to be seen.

Atherosclerosis↗

Human cytomegalovirus seropositivity is associated with impaired vascular function.

BACKGROUND: Herpesvirus infection is a possible risk factor for atherogenesis, and diabetics may be at particular risk. Endothelial dysfunction is an early marker for atherosclerosis, and the present study tests the hypotheses that (1) prior infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) is associated with endothelial dysfunction and (2) this may be more marked in diabetics. METHODS AND RESULTS: Serum samples were tested for anti-IgG antibodies to CMV and HSV from 400 subjects (mean age for diabetics and nondiabetics, 37.8+/-4.3 and 37.9+/-3.7 [SD]). We also assessed Helicobacter pylori and Chlamydia pneumoniae serology. Coronary atheroma was quantified by means of electron beam computed tomography. Subjects (n=157) underwent venous occlusion plethysmography with acetylcholine, bradykinin, glyceryl trinitrate, norepinephrine, and l-NG-monomethyl-l-arginine. Individuals who were seropositive for CMV had reduced responses to bradykinin (P=0.005) and glyceryl trinitrate (P=0.006). The reduced response to bradykinin remained significant (P=0.045) after adjusting for the response to glyceryl trinitrate and was independent of conventional risk factors. Positive serology for the other organisms did not have an independent effect on reactivity. There was a weaker association between CMV and coronary artery calcification (P=0.09). Positive serology for each of the other pathogens did not affect reactivity, but there was a relation between total pathogen burden and impaired vascular reactivity. No significant differences were found between diabetics and nondiabetics. CONCLUSIONS: This study shows that CMV-seropositive individuals have endothelial dysfunction and impaired responses to NO. This association was independent of conventional risk factors and may be associated with increased atherosclerosis burden.

Adult↗

Chronic stress accelerates atherosclerosis in the apolipoprotein E deficient mouse.

Conventional cardiovascular risk factors such as cholesterol and blood pressure do not account fully for variation in coronary heart disease suggesting the involvement of additional mechanisms. We have examined the effects of a chronic psychological stress protocol on the development of atherosclerosis in the apolipoprotein E knockout mouse. We observed a 3-fold increase in staining for atheroma accompanied by a 10-fold increase in corticosterone concentrations in mice stressed for 12 weeks. These data suggest that chronic mild stress can induce or accelerate the development of atherosclerosis.

Animals↗