Ad Blann

The relationship of circulating endothelial cells to plasma indices of endothelial damage/dysfunction and apoptosis in acute coronary syndromes: implications for prognosis

Summary.  Background: While coronary artery disease has been linked to both endothelial damage and cellular apoptosis, their inter‐relationships and impact on cardiovascular (CV) outcomes has been barely explored. Aims: First, we investigated the inter‐relationships between circulating endothelial cells (CECs, and index of endothelial damage) and circulating plasma markers of endothelial damage/dysfunction [von Willebrand factor (VWF), soluble E selectin (sEsel)] and apoptosis [soluble Fas (sFas), Fas ligand (sFasL) and their ratio, sFas/sFasL] in patients presenting with acute coronary syndrome (ACS). Second, we assessed their prognostic values for major adverse CV events (MACE) in ACS. Methods: We studied 211 patients with ACS, who were compared with 60 healthy controls (HC) and 45 ‘disease controls’ (patients with stable coronary artery disease, CAD). Simultaneous blood samples for CECs (immunobead method), VWF, sESel, sFas and sFasL (ELISA) were taken within 24 h of presentation of ACS and at 48 h post admission. Results: CEC, sEsel and VWF levels were significantly higher among the ACS groups compared with the CAD and HC (P < 0.05) groups. sFas was higher (P = 0.016) and sFasL lower (P = 0.021) in ACS compared with controls (HC and CAD). There was a significant increase in sFas/sFasL ratio with increasing disease severity (P = 0.0004). There were significant correlations between CECs and both VWF and sEsel (both P < 0.01) but no correlations between CECs and either sFas or sFas ligand. On univariate survival analysis, CECs were associated with an increased risk of both MACE [hazard ratio (HR) 2.4 (95% CI 1.2–4.1); P = 0.009] and cardiovascular death [HR 2.95 (95% CI 1.01–8.81); P = 0.047]. On multivariate Cox regression analysis, only VWF (and not CECs) remained as an independent predictor of MACE [HR 1.02 (95% CI 1.005–1.040); P = 0.009]. Conclusion: CECs were associated with abnormal plasma indices of endothelial damage/dysfunction and not apoptosis, despite abnormalities of all these markers being associated with ACS. VWF remained as an independent predictor of MACE, on multivariate analysis.

Intracardiac expression of markers of endothelial damage/dysfunction, inflammation, thrombosis, and tissue remodeling, and the development of postoperative atrial fibrillation

Summary.  Background: Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG), and may have an inflammatory and/or thrombotic etiology. We sought to determine the expression of inflammatory (interleukin [IL]‐6), thrombotic (tissue factor and von Willebrand factor [VWF]) and remodeling (matrix metalloproteinase [MMP]‐9 and tissue inhibitor of metalloproteinase [TIMP]‐1) markers by left atrial appendage (LAA) and right atrial appendage (RAA) tissue in the prediction of postoperative AF. We determined whether the tissue expression of markers of certain different pathophysiologic mechanisms predicted the development of AF after CABG. Methods: LAA and RAA tissue was excised during CABG in 100 patients free of AF and inflammation. Tissue marker expression was quantified by immunohistochemistry and was related to 30‐day postoperative AF. Results: Overall, there were no significant differences in staining intensity of any marker between LAA tissue and RAA tissue. However, more intense expression of VWF by LAA tissue predicted the 30 patients with postoperative AF as compared with those free of AF (P = 0.006). IL‐6, MMP‐9 and TIMP‐1 expression by RAA and LAA epicardial tissue was stronger than expression by endocardium or cardiomyocytes (all P < 0.025) but failed to predict AF. Conclusion: In this study, one of the largest to investigate tissue expression of pathophysiologic markers in relation to postoperative AF, we show that more intense expression of VWF by LAA tissue is a significant predictor of postoperative AF. This points towards a possible role of endothelial damage/dysfunction (as reflected by VWF changes) in the pathogenesis of postoperative AF.

Ethnic differences in common carotid intima-media thickness, and the relationship to cardiovascular risk factors and peripheral arterial disease: the Ethnic-Echocardiographic Heart of England Screening Study.

OBJECTIVE To compare the mean and maximum common carotid intima-media thickness (CCIMT) in Blacks (Black Caribbean and Black African) and South Asians (People originating from India, Pakistan and Bangladesh) in a population survey and make associations with established cardiovascular risk factors and peripheral arterial disease (PAD). PATIENTS AND METHODS A subset of 492 (293 South Asians and 199 Blacks) out of 572 participants aged ≥ 45 years recruited in a sub-study to the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) epidemiological study had mean and maximum CCIMT measured. A questionnaire, anthropometric measurements and Ankle Brachial Pressure Index (ABPI) and Intermittent Claudication assessments were made. RESULTS Black participants had greater mean but not maximum CCIMT when compared to South Asians overall (P = 0.022), in men (P = 0.04) and in women (P = 0.044). Black ethnicity was an independent predictor of CCIMT even after adjustment for traditional cardiovascular risk factors (P < 0.05). After adjustment for age, ethnicity and traditional cardiovascular risk factors, the presence of PAD remained independently predictive of mean (P = 0.019) and maximum (P = 0.012) CCIMT. CONCLUSION Black ethnicity is related to greater mean and maximum CCIMT when compared to South Asians, even after adjusting for traditional cardiovascular risk factors. The presence of PAD independently predicts mean and maximum CCIMT adjusting for ethnicity, age and cardiovascular risk factors.

The contribution of cardiovascular risk factors to peripheral arterial disease in South Asians and Blacks: a sub-study to the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study

OBJECTIVE To determine whether differences exist in prevalence of peripheral arterial disease (PAD) between South Asians (people originating from India, Pakistan and Bangladesh) and Blacks (Black Caribbean and Black African), the two largest minority ethnic groups in the UK. To determine if associations with cardiovascular risk factors and this disease differ between these two ethnic groups. PATIENTS AND METHODS We recruited 572 patients (356 South Asian and 216 Blacks) > or = 45 years as a sub-study to a community screening project, the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study. All subjects completed an interviewer-led questionnaire, anthropometric measurements and blood sampling. Ankle brachial pressure index (ABPI) was calculated and intermittent claudication was assessed using the Edinburgh Claudication Questionnaire. The presence of PAD was defined as ABPI <0.9. RESULTS The mean age was 62 years overall with no difference between the two ethnic groups. The prevalence of PAD was 13.2% [95% confidence interval (CI) 9.7-16.7] in South Asians and 10.2% (95% CI 6.2-14.2) in Blacks with no significant difference between the two ethnic groups. The prevalence of PAD was higher in South Asian women than Black women (16.3 vs. 6.1%; P = 0.011). No difference in prevalence was found in men (11 vs. 14% P = 0.47, in South Asians and Blacks, respectively). The prevalence of intermittent claudication was 0.9% (95% CI 0.11-1.63). On multivariate logistic regression, mean systolic blood pressure, diabetes, smoking and male sex were independently associated with PAD in South Asians (P = 0.016, 0.022, 0.037 and 0.008, respectively). In Blacks, only age remained independently associated with PAD on multivariate logistic regression (P = 0.003). CONCLUSION The prevalence of PAD is similar in South Asians and Blacks, and similar to levels reported in pre-dominantly White populations. South Asian women had a higher prevalence of PAD than Black women, which is not explained by traditional cardiovascular risk factors.

Hemostatic cardiovascular risk factors, common carotid–intima medial thickness and peripheral arterial disease in South Asians and African Caribbeans: a substudy to the Ethnic‐Echocardiographic Heart of England Screening (E‐ECHOES) Study

Summary.  Objective: To determine whether ethnic differences exist in inflammatory (interleukin‐6 and C‐reactive protein) and hemostatic biomarkers (soluble P‐selectin [sP‐sel], von Willebrand factor [VWF], and fibrin D‐dimer) between South Asian (people originating from India, Pakistan, and Bangladesh) and African Caribbean (Black Caribbean and Black African) groups, the two largest minority ethnic groups in the UK; and to determine associations between these biomarkers and common carotid intima–media thickness and peripheral artery disease (PAD). Patients and methods: We recruited 572 subjects (356 South Asian and 216 Black) aged ≥ 45 years as a substudy to a community screening project, the Ethnic‐Echocardiographic Heart of England Screening (E‐ECHOES) study. All subjects completed an interviewer‐led questionnaire, anthropometric measurements were taken, and blood sampling was performed if consent was granted. Ankle brachial pressure index (ABPI) was calculated, and the common carotid intima–media thickness (CCIMT) was measured. PAD was defined as ABPI < 0.9. ELISA was used to quantify inflammatory and hemostatic biomarkers. Results: The incidence of hypertension (> 70%) and diabetes (> 27%) was high, but non‐significantly different between the two ethnic groups. South Asians had higher platelet count and sP‐sel levels than African Caribbeans (P < 0.0001 for both), despite there being no significant difference in antiplatelet medication. African Caribbeans had higher D‐dimer levels (P = 0.0052). Among South Asians, VWF correlated with ABPI (P = 0.047) and mean (P = 0.002) and maximum CCIMT (P = 0.011) on univariate analysis, and remained an independent predictor of mean and maximum CCIMT on multivariate analysis with traditional cardiovascular risk factors (P = 0.034 and P = 0.046, respectively). In African Caribbeans, D‐dimer levels were was higher in PAD than in normal ABPI participants (P = 0.04), and was associated with ABPI in both univariate analysis (P = 0.014) and multivariate analysis (P < 0.0001) with traditional cardiovascular risk factors. Conclusion: Ethnic differences are evident in inflammatory and hemostatic factors, as well as in their associations with CCIMT and PAD. These may reflect differences in cardiovascular risk factors or pathophysiologic processes that characterize each ethnic group.