Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes.

BACKGROUND: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. METHODS: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. RESULTS: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). CONCLUSION: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. TRIAL REGISTRATION: Not Applicable.

Feature tracking for assessment of diastolic function by cardiovascular magnetic resonance imaging.

AIM: To assess the agreement of cardiovascular magnetic resonance imaging (CMRI) feature-tracking (FT) parameters with echocardiography to diagnose diastolic dysfunction; to determine whether a similar parameter to mitral inflow early diastolic velocity to early diastolic tissue velocity ratio (E/e') can increase accuracy of imaging by dividing the phase contrast (PC) mitral inflow E-wave (E) with a CMRI-FT parameter; to compare the agreement between CMRI-FT and PC diastolic function assessment using echocardiography. MATERIALS AND METHODS: Patients (n=71; 43 abnormal diastolic function) undergoing both CMRI and echocardiography independently were included. Echocardiography was the reference standard. CMRI-FT analysed the short and long axis cine contours. PC images of mitral inflow, tissue velocity, pulmonary vein flow, and left atrial area were assessed. RESULTS: Using CMRI-FT, the area under the curve (AUC) for identifying diastolic dysfunction was >0.80 for radial and circumferential strain, systolic strain rate (SSR), and early diastolic strain rate (DSR). For cases with CMRI-determined left ventricular ejection fraction (LVEF) ≥50% (n=38), circumferential DSR was the only parameter with good accuracy (AUC=0.87; cut-off 0.93/s). E/circumferential DSR ratio and longitudinal strain had high accuracy in all patients (AUC=0.88 and 0.93 respectively) and CMRI-determined LVEF ≥50% (AUC=0.81; cut-off 76.7). Circumferential DSR showed the highest agreement with echocardiography (higher than E/circumferential DSR and PC assessment) in all cases (kappa 0.75; p<0001) and cases with CMRI LVEF ≥50% (kappa 0.73; p<0.0001). CONCLUSIONS: CMRI-FT circumferential DSR showed the highest accuracy for determining diastolic dysfunction with good agreement with echocardiography. Circumferential DSR had higher accuracy than E/circumferential DSR and PC.

The effects of hyperuricaemia on flow-mediated and nitroglycerin-mediated dilatation in high-risk patients.

BACKGROUND AND AIMS: Uric acid is emerging as one of the newer risk markers to consider in the cardiovascular risk assessment because it is demonstrated to be associated with adverse cardiovascular outcomes, particularly in high cardiovascular risk patients. One of the proposed mechanisms involving hyperuricaemia is the development of vascular damage. The aim of this study is to examine the role of hyperuricaemia on vascular function in patients with high cardiovascular risk. METHODS AND RESULTS: We examined the clinical significance of hyperuricaemia in relation to vasomotor response of the brachial artery by using high-resolution ultrasound in 304 subjects with coronary artery disease and/or diabetes. Nitroglycerin-mediated dilatation (NMD) was significantly lower in the hyperuricaemic group compared with the normouricaemic group (12.8 ± 6.9% vs. 16.2 ± 7.7%, p < 0.001), but no significant difference was observed in flow-mediated dilatation (FMD) between the two groups [3.78 (95% CR: 1.5-9.9) vs. 3.88 (95% CR: -2.6 to 9.9), p = 0.78]. Multivariate analysis demonstrated that smoking was the strongest predictor of FMD (b = -0.81, p = 0.02); and that smoking (b = -2.62, p = 0.003), SBP (b = -0.11, p = 0.001), hyperuricaemia (b = -2.11, p = 0.02) and use of nitrates (b = -3.30, p = 0.001) were independent predictors of NMD. CONCLUSION: High cardiovascular risk patients with hyperuricaemia had a lower NMD than those with normouricaemia. Importantly, hyperuricaemia was independently associated with NMD after multivariable adjustments. To further understand the pathophysiological mechanisms involving hyperuricaemia, particularly in the context of impaired NMD, further experimental and clinical studies are needed.

Relationship between parathyroid hormone and subclinical myocardial dysfunction in patients with severe psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk of cardiovascular disease although the mechanism remains unclear. Recent studies have shown that such patients have a high prevalence of vitamin D (vit-D) deficiency and elevated parathyroid hormone (PTH) level. We hypothesized that vit-D deficiency and/or elevated PTH in psoriasis may contribute to left ventricular (LV) dysfunction. METHODS: Seventy-four patients with severe psoriasis with no known cardiovascular disease and 53 age- and gender-matched controls were recruited. All patients underwent detailed transthoracic echocardiography, including speckle tracking derived strains, and plasma levels of 25-hydoxyvitamin D (25-OHD), PTH and cardiac biomarkers including high sensitive C-reactive protein (hs-CRP), high sensitive troponin I (hs-TNI) and brain natriuretic peptide (BNP) were measured. RESULTS: Despite similar systolic and diastolic LV function, patients with severe psoriasis had impaired LV global longitudinal (-18.1 ± 2.6 vs.-19.6 ± 2.9%, P < 0.01) and circumferential strain (-18.7 ± 3.6 vs. -20.8 ± 4.3%, P < 0.01) compared with controls. Patients with severe psoriasis also had a significantly higher PTH (49.9 ± 18.0 vs. 40.5 ± 15.4 pmol/mL, P < 0.01) and hs-CRP (5.7 ± 6.9 vs. 1.9 ± 2.5 pg/mL, P < 0.01), but similar levels of 25-OHD, hs-TNI and BNP (all P > 0.05) compared with controls. Importantly, PTH level was negatively correlated with LV global longitudinal strain (R = -0.30, P < 0.01); and higher PTH level was independently associated with impaired global LV longitudinal strain (R = -0.33, P = 0.04), independent of cardiovascular risk factors, vit-D status and serum biomarkers. CONCLUSIONS: Severe psoriasis patients had an elevated PTH level and suffered from subclinical LV systolic dysfunction as detected by impaired global LV longitudinal strain. Importantly, a higher PTH level was independently associated with impaired global LV longitudinal strain.

Perioperative antithrombotic management in joint replacement surgeries.

OBJECTIVES: To determine optimal perioperative antithrombotic management for patients with cardiac diseases undergoing joint replacement surgeries. DATA SOURCES: MEDLINE and PubMed database search up to January 2013. STUDY SELECTION: Those dealing with perioperative antithrombotic management of patients undergoing orthopaedic operations, especially joint replacement, and also those undergoing general surgery. Various combinations of the following key words were used in our search: "antiplatelet", "antithrombotic", "anticoagulant", "coronary stent", "perioperative", "venous thromboembolism", "cardiovascular", "surgery", "orthopaedic", "knee replacement", "hip replacement", "joint replacement", and "arthroplasty". DATA EXTRACTION: Literature review, original articles, and best practice guidelines. DATA SYNTHESIS: Patients should be stratified according to their risk of developing arterial thromboembolism in order to decide the most appropriate perioperative antiplatelet or anticoagulant regimen for them. After recent coronary stenting, including bare-metal stents implanted within 6 weeks and drug-eluting stents implanted within 6 months, surgery should be deferred. For venous thromboembolism prophylaxis in patients already on aspirin, the dosage should be adjusted as necessary or additional low-molecular-weight heparin administered. CONCLUSION: The perioperative management of patients with cardiac diseases in receipt of antithrombotic agents is based upon a delicate balance between the perceived risk of arterial thromboembolism and the perceived risk of perioperative bleeding. One must exercise good judgement in deciding the most appropriate perioperative antithrombotic regimen. Venous thromboembolism is also a common problem after joint replacement surgeries. For patients already on aspirin, optimal venous thromboembolism prophylaxis is still being debated.

Garlic intake is an independent predictor of endothelial function in patients with ischemic stroke.

OBJECTIVES: To investigate the effects of garlic on endothelial function in patients with ischemic stroke (ISS). DESIGN: Cross-sectional study. PARTICIPANTS: 125 Chinese patients with prior ISS due to athero-thrombotic disease were recruited from the outpatient clinics during July 2005 to December 2006. MEASUREMENTS: Daily allium vegetable intake (including garlic, onions, Chinese chives and shallots) was ascertained by means of a validated food frequency questionnaire for Chinese and brachial artery flow-mediated dilatation (FMD) was measured using high-resolution ultrasound in all subjects. RESULTS: The mean age of the study population was 65.9±11.1 years and 69% were males. Mean allium vegetable intake and garlic intake of the study population was 7.5±12.7g/day and 2.9±8.8g/day respectively. Their mean FMD was 2.6±2.3%. Daily intake of total allium vegetable (r=0.36, P<0.01) and garlic (r=0.34, P<0.01) significantly correlated with FMD. Using the median daily allium intake as cut-off (3.37g/day), patients with a low allium intake <3.37g/day was noted to have a lower FMD compared to those with a normal allium intake (2.1±2.1% versus 3.0±2.4%, P<0.05). After adjusting for confounding factors, multi-variate analysis identified that daily allium vegetable (B=0.05, 95% confidence interval: 0.02, 0.09, P<0.01) and garlic (B=0.07, 95% confidence interval: 0.02, 0.12, P<0.01) intake, but not onions, Chinese chives and shallots were independent predictors for changes in FMD in patients with ISS. CONCLUSIONS: Daily garlic intake is an independent predictor of endothelial function in patients with ISS and may play a role in the secondary prevention of atherosclerotic events.

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease.

PURPOSE: The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown. METHODS: A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m(2), and the remaining patients were considered to be without significant CKD (eGFR ≥ 60 mL/min/1.73m(2)). RESULTS: Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value = 50; sensitivity 75 % and specificity 75 %). CONCLUSION: The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.

Increased dietary fruit intake was associated with lower burden of carotid atherosclerosis in Chinese patients with Type 2 diabetes mellitus.

BACKGROUND: Previous studies demonstrated that high fruit consumption was associated with a lower risk of cardiovascular events in patients with Type 2 diabetes mellitus. However, the relationship between fruit intake and carotid atherosclerosis in these patients is unknown. We studied the relationship between dietary fruit intake and carotid intima-media thickness in patients with Type 2 diabetes. METHODS: A total of 255 Chinese patients with Type 2 diabetes were recruited. Dietary fruit intake was assessed by a validated food-frequency questionnaire, and carotid intima-media thickness was measured by high-resolution ultrasonography. RESULTS: Among patients with three different tertiles of fruit intake (14.5 ± 8.6 vs. 41.5 ± 7.1 vs. 92.6 ± 39.7 g/day), there was no difference in their clinical characteristics (all P > 0.05). Patients with the highest tertile of fruit intake had a significantly higher BMI and diastolic blood pressure than those with the lowest tertile intake. Furthermore, serum high-sensitivity C-reactive protein, 8-isoprostane and superoxide dismutase were similar among the three tertiles of patients (all P > 0.05). However, patients with the highest tertile of fruit intake had lower carotid intima-media thickness (0.97 ± 0.02 vs. 1.08 ± 0.03 mm, P = 0.046) and prevalence of carotid plaque (11.76 vs. 1.18%, P = 0.022) than those with the lowest tertile of fruit intake. Multivariate regression analysis revealed the highest tertile of fruit intake (ß = -0.086, P = 0.049) was independently associated with carotid intima-media thickness. CONCLUSIONS: Our results demonstrated that, in Chinese patients with Type 2 diabetes, higher dietary fruit intake was associated with a lower burden of carotid atherosclerosis as reflected by lower carotid intima-media thickness and prevalence of carotid plaque.

Periodontal therapy decreases serum levels of adipocyte fatty acid-binding protein in systemically healthy subjects: a pilot clinical trial.

BACKGROUND AND OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) is expressed in adipocytes, macrophages and microvascular endothelial cells, and it plays a central role in inflammation, atherosclerosis and metabolic responses. This pilot study investigated the effect of nonsurgical periodontal therapy on the serum levels of A-FABP in subjects with chronic periodontitis. MATERIAL AND METHODS: A pilot clinical trial was conducted in 24 otherwise healthy Chinese subjects with moderate to severe chronic periodontitis. The treatment group (n = 12) received nonsurgical periodontal therapy immediately, whereas in the control group (n = 12) the treatment was delayed for 3 months. The serum levels of A-FABP were measured by ELISAs. Other inflammatory and endothelial biomarkers and periodontal conditions were evaluated at baseline and at the 3-month follow-up appointment. RESULTS: A-FABP levels decreased significantly in the treatment group compared with the control group (treatment effect: -1.7 ng/mL; 95% confidence interval: -2.8 to -0.6; p = 0.003). The treatment also significantly improved periodontal conditions but had no significant effect on other biomarkers. In the multivariable regression model, the change in the percentage of sites with detectable plaque was significantly associated with the change in the level of A-FABP (beta: 0.04, 95% confidence interval: 0.01-0.06, p = 0.004). CONCLUSION: Within the limitations of this pilot study, the current findings suggest that treatment of periodontitis may significantly decrease the serum levels of A-FABP. Further longitudinal study with a large sample size is warranted to confirm this finding and elaborate the relevant clinical implications.

Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.

OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and increased risk of cardiovascular disease events. However, the prevalence and extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and carotid atherosclerosis were compared in 70 patients with psoriasis (46 ± 9 years, 71% male) without known cardiovascular disease or joint involvement and 51 age- and gender-matched healthy control subjects (45 ± 7 years, 71% male). Systemic inflammation was assessed by the level of high-sensitivity C-reactive protein (hs-CRP). Coronary atherosclerosis was determined by the coronary calcification score (CCS) measured by multi-detector computed tomography. Carotid atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima-media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher degree of coronary atherosclerosis estimated by the mean CCS (67.4 ± 349.2 vs. 0.5 ± 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly greater in patients with psoriasis than in control subjects (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was independently associated with increased cIMT. Amongst participants with no traditional cardiovascular disease risk factors, hs-CRP level was higher in patients with psoriasis than in controls. CONCLUSION: The present results demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid arteries in patients with psoriasis, but not in age- and gender-matched control subjects. Low-grade inflammation could explain the presence of premature atherosclerosis in patients with psoriasis.

Prospective observational study of isoflavone and the risk of stroke recurrence: potential clinical implications beyond vascular function.

BACKGROUND: Whether isoflavone has any effect on recurrent cardiovascular events is unknown. OBJECTIVE: To investigate the relations between isoflavone intake and the risk of stroke recurrence. SUBJECTS AND METHODS: We recruited 127 consecutive patients with prior history of atherothrombotic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. RESULTS: Median isoflavone intake was 6.9 (range: 2.1 - 14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4 - 27.6] mth versus 5.0 [range: 4.1 - 5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4 - 27.6] mth versus 4.0 [range: 2.4 - 5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03 - 0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03 - 0.84], risk reduction 84%, p=0.030). CONCLUSIONS: Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE independent of baseline vascular function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.

Prognostic role of coronary calcification in patients with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVES: To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE). METHODS: A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events. RESULTS: Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events. CONCLUSIONS: Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

Adverse systemic arterial function in patients with selenium deficiency.

BACKGROUND: Experimental studies have shown that selenium is involved in the synthesis of selenoproteins which might contribute to cardiovascular protection. However, the relationship between selenium deficiency and vascular function in clinical context remains unknown. OBJECTIVE: To investigate for any relationship between selenium deficiency and systemic arterial function in patients with high risk of vascular events. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 306 consecutive patients with high risk for cardiovascular events (coronary artery disease 35%, acute/ recurrent ischemic stroke 40%, diabetes mellitus 54%) followed up at internal medicine outpatient clinics. MEASUREMENTS: Non-invasive brachial-ankle pulse wave velocity (PWV) was determined using vascular profiling system (VP-2000). Long-term intake of selenium was determined by a validated food frequency questionnaire. RESULTS: Mean daily selenium intake was 59.5 ± 52.1 mcg/day, and mean PWV was 1782.4 ± 418.4 cm/s. Patients with selenium intake <10th percentile had significantly higher PWV as compared to patients with intake ≥ 10th percentile (1968.2 ± 648.9 cm/s versus 1762.2 ± 381.6 cm/s, P=0.010). After adjusting for potential confounders including age, gender, history of hypertension, hyperlipidemia, diabetes and cardiovascular disease, smoking status, use of cardiovascular medications, waist-hip ratio, education/ financial status, physical activity, calorie intake and intake of antioxidant vitamins, deficient selenium intake <10th percentile remained independently predictive of increased PWV by +363.4 cm/s [95% CI: 68.1 to 658.6, P=0.016, relative increase 21%]. CONCLUSIONS: Selenium deficiency is associated with adverse arterial function in patients with high risk for vascular events.

Hypertension and atrial fibrillation: epidemiology, pathophysiology and therapeutic implications.

Hypertension is one of the most important risk factors associated with atrial fibrillation (AF) and increased the risk of cardiovascular events in patients with AF. However, the pathophysiological link between hypertension and AF is unclear. Nevertheless, this can be explained by the hemodynamic changes of the left atrium secondary to long standing hypertension, resulting in elevated left atrium pressure and subsequently left atrial enlargement. Moreover, the activation of renin-angiotensin-aldosterone system (RAAS) activation in patients with hypertension induces left atrial fibrosis and conduction block in the left atrium, resulting in the development of AF. Accordingly, recent studies have shown that effective blockage of RAAS by angiotensin converting enzyme inhibitors or angiotensin receptor antagonist may be effective in both primary and secondary prevention of AF in patients with hypertension, although with controversies. In addition, optimal antithrombotic therapy, blood pressure control as well as rate control for AF are key to the management of patients with AF.

Serum adipocyte fatty acid-binding protein associated with ischemic stroke and early death.

OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) is an adipokine shown to have adverse metabolic and proinflammatory effects, and contributes to atherosclerosis in mice. However, its role in cardiovascular diseases in humans remains to be established. In this case-control study, we investigated the association of serum A-FABP with ischemic stroke, and examined its association with early mortality. METHODS: Serum A-FABP was measured, using ELISA, in 306 subjects with acute ischemic stroke and 306 age-, sex-, and body mass index-matched controls. All controls were free of cardiovascular diseases. Serum A-FABP was also measured in another 60 ischemic stroke subjects who died within 3 months of acute stroke. RESULTS: Serum A-FABP was higher in subjects with ischemic stroke as compared to controls (19.6 ng/mL [14.3-28.4 ng/mL] vs 15.2 ng/mL [10.6-23.6 ng/mL] in men and 32.4 ng/mL [24.5-45.7 ng/mL] vs 22.0 ng/mL [14.3-34.0 ng/mL] in women, stroke vs control, p<0.001). On logistic regression analyses with the model including hypertension, diabetes, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, lipid-lowering treatment, smoking, and A-FABP, serum A-FABP was independently associated with stroke (odds ratio 2.10, 95% confidence interval 1.50-2.94, p<0.001), and the associations of A-FABP with ischemic stroke were additive to conventional risk factors, as demonstrated on likelihood ratio tests (p<0.001). Furthermore, high serum A-FABP was associated with increased 3-month mortality in ischemic stroke subjects (odds ratio 2.65, 95% confidence interval 1.18-5.96, p=0.018), independent of age and NIH Stroke Scale score. CONCLUSIONS: Serum A-FABP was significantly associated with ischemic stroke in our case-control study, and may serve as a useful prognostic indicator for early mortality.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

BACKGROUND: Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear. OBJECTIVES: We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function. METHODS: Fifty-two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age- and sex-matched controls. Baseline demographics and high-sensitivity C-reactive protein (hs-CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index. RESULTS: Patients with psoriasis had significantly higher hs-CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L(-1), P < 0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s(-1) , P < 0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs-CRP with baPWV (r = 0·51, P < 0·01) and with PASI (r = 0·48, P < 0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs-CRP (P < 0·05), but does not predict PAT index. Each mg L(-1) increase in hs-CRP accounted for an increase in baPWV of +0·12 m s(-1) (95% confidence interval 0·01-0·22, P = 0·03). CONCLUSIONS: Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs-CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.

Low circulating level of CD133+KDR+cells in patients with systemic sclerosis.

BACKGROUND: Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial. OBJECTIVES: To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients. METHODS: Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay. RESULTS: SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/µl, p<0.001) as well as FMD% (4.8% vs. 7.8%, p<0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/µl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter. CONCLUSIONS: Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.