Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients

Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear. Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects. Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16–1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01–1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54–0.90]; p = 0.005, 0.76 [0.61–0.94]; p = 0.012, and 1.30 [1.03–1.62]; p = 0.025, respectively). Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.     

LDL cholesterol as a novel risk factor for contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention

Background: Low density lipoprotein cholesterol (LDL-C) is associated with endothelial dysfunction, inflammation and increased vasoconstriction, which are involved in the development of contrast-induced acute kidney injury (CI-AKI). However, whether LDL-C is an independent risk factor of CI-AKI in patients undergoing percutaneous coronary intervention (PCI) is unknown. Methods: We prospectively enrolled 3236 consecutive patients undergoing PCI between January 2010 and September 2012. Multivariate logistic regression analysis was used to determine whether LDL-C is an independent risk factor of CI-AKI. CI-AKI was defined as an absolute increase in serum creatinine of ≥0.5 mg/dL or ≥25% over the baseline value within 48–72 h after contrast exposure. Results: CI-AKI was observed in 338 patients (10.4%). Patients with CI-AKI had a significantly higher rate of in hospital mortality (4.4% vs. 0.5%, p < 0.001), and significantly higher rates of other in hospital complications compared with those without CI-AKI. The LDL-C quartiles were as follows: Q1 (<2.04 mmol/L), Q2 (2.04–2.61 mmol/L), Q3 (2.61–3.21 mmol/L) and Q4 (>3.21 mmol/L). Patients with high baseline LDL-C levels were more likely to develop CI-AKI and composite end points including all-cause mortality, renal replacement therapy, non-fatal myocardial infarction, acute heart failure, target vessel revascularization or cerebrovascular accident during the observation period of hospitalization (8.9%, 9.9%, 10.5%, 12.6%, p = 0.001, and 5.0%, 5.2%, 6.1%, 8.1%, respectively; p = 0.007). Univariate logistic analysis showed that LDL-C levels (increment 1 mmol/L) were significantly associated with CI-AKI (odds ratio = 1.25, 95% confidence interval (CI), 1.11–1.39, p < 0.001). Furthermore, LDL-C remained a significant risk factor of CI-AKI (odds ratio = 1.23, 95% CI, 1.04–1.45, p = 0.014), even after adjusting for potential confounding risk factors. Conclusions: Measurement of plasma LDL-C concentrations in patients undergoing PCI may be helpful to identify those who are at risk of CI-AKI and poor in hospital outcomes.     

Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes

Background: Previous studies have shown that computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD) predicts short term adverse events. However, there is no current data on whether identifying atherosclerosis on CTA impacts outcomes. We performed a case–control study to assess whether information from CTA can improve outcomes. Methods: 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD were matched to 1706 patients who underwent standard of care in an academic cardiology clinic. Patients were propensity-matched by gender, age, ethnicity, CAD risk factors and follow-up duration. The primary outcome measure was all-cause mortality. Multivariable Cox proportional hazards models incorporated age, gender and traditional risk factors for coronary disease as well as pre-test probability of CAD. Results: There were no significant differences in age, gender, conventional risk factors between groups (p > 0.05). During a mean follow up of 80 ± 11 months, the overall death rate was 6.3% (270 deaths). Death rate was significantly lower in CTA group (n = 106, 4.2%) as compared to the control group (n = 184, 10.8%, p = 0.001). Event free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Risk-adjusted hazard ratio of death were 2.5 (95%CI: 1.6–6.7, p = 0.003) in standard of care cohort as compared to CTA group. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32%, p = 0·0001. Conclusions: Improved knowledge of atherosclerosis or increased anti-atherosclerotic therapies among those undergoing CTA may have contributed to improved survival. Our results provide evidence of potential benefit from scanning for atherosclerosis with CTA in symptomatic patients. Large randomized trials are warranted.     

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.     

Non-HDL cholesterol is a better target for predicting periprocedural myocardial injury following percutaneous coronary intervention in type 2 diabetes

Objective: Non-HDL cholesterol (non-HDL-C) has recently been recommended as a first target for dyslipidemia management. We previously reported that LDL cholesterol (LDL-C) and non-HDL-C levels were similarly associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in patients with coronary artery disease. Here we investigated the comparative prognostic value of non-HDL-C and LDL-C for PMI following PCI in type 2 diabetes (T2D). Methods: We prospectively enrolled 1194 consecutive T2D patients with normal preprocedural cTnI undergoing PCI. Patients were divided into the two groups: group A [glycated hemoglobin (HbA1c) < 7%, n = 567] and group B (HbA1c ≥ 7%, n = 627). PMI was evaluated by cTnI analysis within 24 h. The relationship of preprocedural non-HDL-C and LDL-C levels with peak cTnI values after PCI was examined. Results: Patients in group B, with higher preprocedural non-HDL-C levels, had higher postprocedural cTnI levels (β = 0.102, P = 0.011). In the multivariable model, a 1-SD increase in non-HDL-C produced a 30% and 33% increased risk of postprocedural cTnI >3 × upper limit of normal (ULN) and >5 × ULN in group B, respectively. However, neither LDL-C nor group A patients were affected. Furthermore, patients with non-HDL-C levels ≥130 mg/dl compared with non-HDL-C levels ≤100 mg/dl were associated with a 83.3% and 71.7% increased risk of postprocedural cTnI >3 × ULN and >5 × ULN in group B, respectively. Conclusions: In poorly-controlled diabetic patients (HbA1c ≥ 7%) undergoing PCI, non-HDL-C but not LDL-C was independently associated with and increased risk of PMI, and non-HDL-C levels ≥130 mg/dl had a worse PMI risk profile compared with non-HDL-C levels <100 mg/dl.     

Metabolomics signature improves the prediction of cardiovascular events in elderly subjects

Aims

Age is one of the most important determinants of cardiovascular health, therefore the management of cardiovascular diseases (CVD) in elderly people entails great challenge. A possible explanation of vascular senescence process is the mitochondrial damage and dysfunction. We hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events (MACEs) in elderly people, improving the clinical standard cardiovascular risk factors.

Methods and results

Targeted-mass-spectrometry-based profiling of 49 metabolites was performed in a group of very old participants (n = 67, mean age = 85 ± 3 years) with a high rate of previous CVD (68%). Principal Component Analysis, Random Survival Forest analysis and Cox proportional hazards regression modeling were used to evaluate the relation between the metabolite factors and recurring MACEs. We tested discrimination ability and reclassification of clinical and metabolomic models.At follow-up (median = 3.5 years), 17 MACEs occurred (5 cardiovascular deaths, 1 nonfatal myocardial infarction, 7 nonfatal strokes and 4 peripheral artery surgeries) (incidence = 7.3% person-years). Metabolite factor 1, composed by medium- and long-chain acylcarnitines, and factor 7 (alanine) were independently associated with MACEs, after adjustment for clinical CV covariates [HR = 1.77 (95%CI = 1.11–2.81, p = 0.016) and HR = 2.18 (95%CI = 1.17–4.07, p = 0.014), respectively]. However, only factor 1 significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 7%, p = 0.01) and correctly reclassifying 41% of events and 37% of non-events resulting in a cNRI = 0.79 (p = 0.005).

Conclusions

Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.     

The impact of female sex on long-term survival of patients with severe atherosclerosis undergoing endarterectomy

Objectives. Long-term age- and sex-specific mortality data in patients undergoing carotid endarterectomy (CEA) and iliac/femoral endarterectomy (FEA) are scarce. We examined long-term mortality in these patient groups, stratified by age and sex. Methods. Between 2002 and 2012, 1771 patients (1200 men, 571 women) treated by CEA, and 685 patients (495 men, 190 women) who underwent FEA, were included and linked to the national mortality registry of the Netherlands. Absolute mortality risks during follow-up were analyzed by life-table and Kaplan Meier survival analyses in two age groups and stratified by sex, and compared to a matched sample from the general population. In addition, multivariable Cox regression analyses were performed. Results. After CEA, with a median follow-up duration of 4.3 years (interquartile range 2.0–7.1), 298 all-cause deaths had occurred in men (25%) and 105 (18%) in women. As in the general population, cumulative survival after CEA was significantly better in women compared to men (P = 0.002) and absolute CEA-associated mortality risk in women was similar to that of the general population. For FEA patients, mortality risk was worse than for CEA patients and the general population in both sexes and surprisingly, female sex did not have a favorable effect on survival. Following FEA, 130 men (26%) and 51 women (27%) died after a median follow-up time of 3.0 years (interquartile range 1.5–5.9). Stratifying by age, and adjusting for cardiovascular risk factors did not change these trends. Conclusions. Long-term mortality after CEA is higher in men than in women, and in women mortality risk is similar to the general population. After FEA, the benefit of women as seen after CEA is lost.     

Circulating IGFBP-2 levels are incrementally linked to correlates of the metabolic syndrome and independently associated with VLDL triglycerides

Objective: To assess whether plasma IGFBP-2 is independently associated with components of the lipoprotein-lipid profile and to suggest a cutoff value that could identify subjects with the features of the metabolic syndrome. Methods: In this cross-sectional study, 379 Caucasian men from the general population and covering a wide range of BMI were recruited through the media. Subjects with type 2 diabetes, BMI values > 40 kg/m², or taking medication targeting glucose or lipid metabolism or blood pressure were excluded. Anthropometric data were collected and plasma IGFBP-2 concentrations, glucose tolerance and an extensive plasma lipid profile were determined after an overnight fast. Results: Subjects with low IGFBP-2 levels were characterized by increased fat mass (p < 0.0001), impaired insulin sensitivity (p < 0.0001) and higher plasma triglyceride (TG) levels (p < 0.0001). When divided into 6 quantiles, only subjects with the highest IGFBP-2 levels (>221.5 ng/mL) did not meet the NCEP ATP III criteria for the clinical diagnosis of the metabolic syndrome. In addition, circulating IGFBP-2 levels were significantly associated with VLDL-TG (r = −0.51, p < 0.0001) and HDL-C (r = −0.27, p < 0.0001) levels. After adjustments, plasma IGFBP-2 was found to be independently associated with VLDL-TG levels but not with HDL-C concentrations. Conclusions: In our cohort, IGFBP-2 levels <221.5 ng/mL are incrementally associated with a detrimental plasma lipoprotein-lipid profile. After adjustment for covariates, IGFBP-2 remained independently associated with VLDL-TG but not HDL-C levels. This study supports further investigations in other populations and validation of IGFBP-2 as a biomarker of early dyslipidemia.     

Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease

Objective: Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients. Methods and results: Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden. Conclusion: These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients.     

An Approach to the Rational Use of Revascularization in Heart Failure Patients

The most common cause of heart failure with reduced ejection fraction (HFrEF) is coronary artery disease. A multitude of factors come into play when deciding whether a patient with HFrEF and coronary artery disease should have coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention, or medical therapy alone. For candidates for percutaneous coronary intervention and CABG, evidence from large registries would suggest that patients with 2-vessel coronary artery diseases and proximal left anterior descending disease and all patients with 3-vessel coronary artery disease do better with CABG. For patients that are candidates for medical therapy with or without CABG, the results of the Surgical Treatment for Ischemic Heart Failure (STICH) trial indicate that with CABG, the reduction of mortality is not statistically significant (hazard ratio [HR], 0.86; P = 0.12). However, CABG is superior in reducing cardiovascular deaths (HR, 0.81; P = 0.05), and the combination of cardiovascular deaths and cardiovascular hospitalizations (HR, 0.74; P < 0.001). Patients undergoing CABG have an upfront risk that is eliminated by 2 years and thereafter do better. The assessment of cardiac viability or reversible ischemia does not appear to be helpful in determining which individuals will improve more with CABG. Patients with severe mitral regurgitation who undergo CABG appear to benefit from simultaneous valve repair but not from the addition of surgical ventricular reconstruction of the left ventricle, although in specific patients this might be considered. The totality of evidence would thus suggest that patients with HFrEF should be evaluated for the possibility of coronary revascularization if they are candidates for CABG.     

Blood pressure disturbances and endothelial dysfunction markers in children and adolescents with type 1 diabetes

Objective: Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. Methods: The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. Results: Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). Conclusions: Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.     

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by F-FDG PET/CT

Objective: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT). Methods/results: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, ¹⁸F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized ¹⁸F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0–147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. Conclusion: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by ¹⁸F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.     

Association between chronic kidney disease and thoracic aortic atherosclerosis detected using transesophageal echocardiography

Objective: Accelerated atherosclerosis occurs with a high frequency in patients with chronic kidney disease (CKD). We evaluated the association between CKD and thoracic aortic plaques using transesophageal echocardiography (TEE). Methods: This study population consisted of 297 patients who underwent TEE. Aortic plaques were evaluated in the proximal thoracic aorta (PTA) (from the ascending aorta to the aortic arch) and the distal thoracic aorta (DTA) (the descending aorta) using TEE. Aortic plaques were defined as complex plaques of ≥4 mm thickness and with ulceration or mobile components. CKD was defined as the estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². The association between CKD and aortic plaques was evaluated using multivariate analysis after adjusting for traditional atherosclerotic risk factors. Results: Patients with CKD (n = 144) had a higher incidence of any plaques and complex plaques compared with those without CKD (n = 153) (85% vs. 47% and 42% vs. 17%, respectively, both P < 0.001). Univariate analysis indicated that the presence of CKD was significantly associated with complex plaques both in the DTA and the PTA (both, P < 0.001); however, multivariate analysis indicated that the presence of CKD was associated with only complex plaques in the DTA (P < 0.05), but not with those in the PTA. Conclusion: The presence of CKD was associated with complex aortic plaques, with this association being stronger for complex plaques in the DTA than those in the PTA.     

Altered lipidome and antioxidative activity of small,dense HDL in normolipidemic rheumatoid arthritis: Relevance of inflammation

Objective: High-density lipoprotein (HDL) particles exert potent antiatherogenic activities, including antioxidative actions, which are relevant to attenuation of atherosclerosis progression. Such activities are enriched in small, dense HDL and can be compromised under conditions of chronic inflammation like rheumatoid arthritis (RA). However, structure–function relationships of HDL largely remain indeterminate. Methods: The relationships between HDL structure and function were evaluated in normolipidemic patients with active RA (DAS28 > 3.2; n = 12) and in normolipidemic age-matched controls (n = 10). Small, dense HDL3b and 3c particles were isolated from plasma or serum by density gradient ultracentrifugation and their physicochemical characteristics, lipidome (by LC/MS/MS) and antioxidative function (as protection of normolipidemic LDL from free radical-induced oxidation) were evaluated. Results: As expected, active RA patients featured significantly elevated plasma levels of high-sensitivity C-reactive protein (hsCRP; p < 0.001) and serum amyloid A (SAA; p < 0.01) relative to controls. Antioxidative activity and weight % chemical composition of small, dense HDL did not differ between RA patients and controls (p > 0.05), whereas HDL phosphosphingolipidome was significantly altered in RA. Subgroup analyses revealed that RA patients featuring high levels of inflammation (hsCRP>10 mg/l) possessed small, dense HDL with reduced antioxidative activities (p < 0.01). Furthermore, antioxidative activity of HDL was inversely correlated with plasma hsCRP (p < 0.01). Conclusions: These data revealed that (i) despite normolipidemic state, the lipidome of small, dense HDL was altered in RA and (ii) high levels of inflammation can be responsible for the functional deficiency of small, dense HDL in RA.     

Self-rated health (SRH) as a predictor of mortality in elderly men living in a medium-size city in Brazil

The objective was to examine the role of SRH as a predictor of mortality in elderly men in a medium-size Brazilian city. In 2 years of follow-up, 120 deaths occurred in the study population, with the following main causes: cardiovascular diseases (40%), neoplasms (22.5%), and respiratory diseases (10%). In practically all of the target variable strata, elderly men with fair or poor SRH showed a higher risk of dying as compared to those with excellent or good SRH. In the final model, the variables fair/poor SRH (hazard risk = HR = 1.88, 95% confidence interval = 95%CI = 1.29-2.72), age (HR = 1.05, 95%CI = 1.03-1.08), public health system as the regular source of care (HR = 1.69, 95%CI = 1.10-2.60), current smoking (HR = 1.94, 95%CI = 1.24-3.04), and acute cardiovascular disease (HR = 1.62, 95%CI = 1.06-2.47) were associated with mortality. We concluded that SRH proved to be a predictive variable for mortality in elderly men after 2 years of follow-up, with nearly a twofold risk of death among men that reported fair or poor health, after adjusting for age, regular use of the public health system, current smoking, and acute cardiovascular disease. Given the importance of poor SRH for predicting mortality in elderly men, health services should incorporate this indicator into health assessments in this population.     

Persistent epicardial adipose tissue accumulation is associated with coronary plaque vulnerability and future acute coronary syndrome in non-obese subjects with coronary artery disease

Objective. Epicardial adipose tissue (EAT) is recognized as a novel risk factor for coronary artery disease (CAD), and its contribution is thought to be stronger in non-obese patients than in obese patients. However, the prognostic impact of the progression of EAT accumulation after comprehensive management for atherosclerotic risk factors remains unclear. This study aimed to investigate whether an increase of the EAT volume during follow-up predicts future acute coronary syndrome (ACS) events in non-obese CAD patients. Methods. This study consisted of 517 non-obese CAD patients (368 men; age, 66 ± 10 years) who underwent serial multidetector computed tomography (MDCT) examinations to evaluate coronary atherosclerosis progression. The MDCT examination was used to assess the severity of stenosis, plaque characteristics, and EAT volume. All patients received comprehensive management to reduce CAD risk factors after the first MDCT examination. The MDCT examination was repeated at 6–24 months, and patients were followed-up for more than 1 year or until the occurrence of ACS events. Results. Of 517 patients, 159 (31%) patients were classified into increase of EAT volume during follow-up, 91 (18%) into decrease of EAT volume during follow-up, and 267 (51%) patients into constant of EAT volume during follow-up. The prevalence of obstructive plaques and MDCT-derived vulnerable features of coronary plaques were significantly elevated in patients with increase of EAT volume during follow-up. In contrast, no significant changes were observed in the other 2 groups. During the follow-up period of 4.1 ± 1.8 years (median 4.4 years) after the second MDCT examination, ACS occurred in 43 (8.3%) patients. Multivariate Cox regression analysis showed that the presence of low-attenuation plaque (hazard ratio [HR]; 1.78, p = 0.04) and napkin-ring sign (HR; 3.74, p < 0.001) at second MDCT examination, and changes of EAT volume per 10 ml (HR; 1.34, p = 0.004) were associated with future ACS events. Conclusion. Patients with increase of EAT volume during follow-up despite comprehensive management for CAD risks had an increased prevalence of obstructive plaques and plaques with high-risk features, which could be associated with unfavorable ACS outcomes in non-obese CAD patients.     

HOMA-IR and the risk of hyperuricemia: A prospective study in non-diabetic Japanese men

Aims

To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia.

Methods

The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35–54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid >416.4 μmol/L (7.0 mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR.

Results

During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR ≤0.66, were 1.42 (95% confidence interval 1.02–1.98) for HOMA-IR 0.67–0.98, 1.20 (0.86–1.68) for HOMA-IR 0.99–1.49 and 1.44 (1.04–1.98) for HOMA-IR ≥1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03–1.28) (p for trend = 0.02).

Conclusions

Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia.     

R2CHADS2 Score and Thromboembolic Events After Catheter Ablation of Atrial Fibrillation in Comparison With the CHA2DS2-VASc Score

Background

A new risk model, the R₂CHADS₂ (Renal Dysfunction, Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) score, was proposed to be a powerful scoring scheme in predicting stroke or systemic embolism in atrial fibrillation (AF). The goal of the present study is to validate the usefulness of the R₂CHADS₂ score among patients with AF after catheter ablation. We also aimed to compare the accuracy of the CHA₂DS₂-VASc (Congestive Heart Failure, Hypertension, Age [≥ 75 y], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 y], Sex [Female]) and R₂CHADS₂ scores for risk stratification of thromboembolic (TE) events after ablation procedures.

Methods

We enrolled a total of 526 patients with AF who underwent catheter ablation. The clinical end point was the occurrence of TE events (ischemic stroke, transient ischemic attack, or other systemic embolisms) during the postablation follow-up.

Results

During a follow-up of 37.5 ± 21.3 months, 14 patients (2.7%) experienced TE events. The R₂CHADS₂ score was an independent predictor of TE events in the multivariate analysis. Patients with an R₂CHADS₂ score of > 2 had a higher event rate compared with those with a score of 0 or 1 (0.5% vs 7.7%). The areas under the receiver operating characteristic (ROC) curves of CHA₂DS₂-VASc and R₂CHADS₂ scores in predicting TE events were 0.832 and 0.872, respectively. The difference between these 2 curves did not reach statistical significance (P = 0.338). In addition, the R₂CHADS₂ score did not improve net stroke risk reclassification over the CHA₂DS₂-VASc score (net reclassification improvement, −0.9%; P = 0.948).

Conclusions

The R₂CHADS₂ and CHA₂DS₂-VASc scores could be used to predict TE events for patients with AF undergoing catheter ablation. The predictive accuracy of both scores were similar in this relatively small cohort undergoing ablation.     

ORAl iMmunosuppressive therapy to prevent in-Stent rEstenosiS (RAMSES) cooperation: A patient-level meta-analysis of randomized trials

Objective: The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis. Methods: We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics. Results: Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24–0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21–0.67], P < 0.001) and late lumen loss (−0.39 mm [−0.67, −0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29–1.53], P = 0.34), death (0.82 [0.25–2.69], P = 0.71), MI (0.58 [0.24–1.39], P = 0.22) and stent thrombosis (0.43 [0.10–1.87], P = 0.26). Conclusion: In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.     

Lack of association between serum gamma-glutamyltransferase and carotid atherosclerosis: The Namwon study

Objectives: There is little evidence for an association between gamma-glutamyltransferase (GGT) and carotid atherosclerosis, an independent predictor of cardiovascular disease. We examined the association between serum GGT and carotid atherosclerotic parameters, including carotid intima-media thickness (IMT) and plaques, in a large general population. Methods: The study population consisted of community-dwelling adults who participated in the baseline survey of the Namwon Study. A total of 9120 subjects aged 45–74 years were included in the analyses. High-resolution B-mode ultrasound was used to measure carotid IMT and to evaluate the presence of carotid plaques. A mean carotid IMT of ≥1.0 mm was classified as ‘high carotid IMT’. Results: Serum GGT levels were classified into quartiles. In a fully adjusted model, we found no linear trend between GGT quartile and mean carotid IMT (P for trend = 0.167). Compared with the first quartile (the reference category), the odds ratios (ORs) and 95% confidence intervals (CIs) for high carotid IMT were 0.89 (0.68–1.16), 1.10 (0.84–1.43), and 0.97 (0.71–1.33) for the second, third, and fourth quartiles (P for trend = 0.754), respectively. The ORs (95% CIs) for carotid plaques were 0.89 (0.77–1.02), 0.95 (0.82–1.10), and 0.94 (0.79–1.11) for the second, third, and fourth quartiles, respectively, in the fully adjusted model (P for trend = 0.644). Conclusions: No significant association of GGT concentration with carotid IMT or plaques was found in this large cross-sectional study. Further longitudinal studies are needed to confirm our findings.