Related Articles

Aim

To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD).

Methods

In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured.

Results

Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role.

Conclusion

Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism.

Serum total lipids (cholesterol and triglyceride), lipoproteins (VLDL, LDL and HDL) and Apolipoprotein-B levels of normal healthy individuals (n=25) and coronary artery disease patients (n=25) were estimated. The objective of the present study was to ascertain the role of apo-B in causation and inheritance of coronary artery disease. It was observed that on an average serum total cholesterol and triglyceride more than 200 mg/dl bring the individuals to a risk of coronary artery disease (CAD) irrespective of the age. CAD patients achieved this value at an early age (35–45 years). Similarly VLDL and LDL levels were found to be significantly raised in CAD patients when compared to that of age matched normal individuals, with patients achieving risk values at an early age. HDL levels were found to be significantly lower in CAD patients as compared to normal individuals. Serum apo-B levels were significantly raised in CAD patients as compared to age matched normal individuals. Patients with positive family history of CAD had raised serum apo-B levels than those having negative family history. A positive coefficient of correlation was observed between serum apo-B and LDL levels suggesting that more the number of Apo-B particles, more will be the synthesis of atherogenic particle (LDL). Patients with negative family history had serum apo-B levels closer to those of normal individuals and in these individuals HDL levels were found to be significantly lowered, suggesting that loss of scavenger role of HDL could be the risk factor responsible for the causation of CAD in these patients, with negative family history of coronary artery disease.

Body fat distribution may be differentially associated with subclinical cardiovascular disease. We sought to examine whether body mass index (BMI), waist circumference (WC), subcutaneous (SAT) and visceral (VAT) adipose tissue are associated with either prevalence of coronary (CAC) or abdominal aortic calcium (AAC) in the Framingham Heart Study. Participants (n=3130, mean age 52 years, 49% women) free of clinical cardiovascular disease from the Framingham Heart Study underwent multidetector computed tomography assessment for quantification of subcutaneous and visceral fat volume and coronary and abdominal aortic calcification. Coronary artery calcification (CAC) and abdominal aortic calcification (AAC) were examined in relation to BMI, WC, SAT, and VAT in age- sex- and multivariable-adjusted models. All measures of adiposity were associated with CAC in age-sex adjusted models (all p-values<0.008). All relations were attenuated in multivariable models (all p-value>0.14). BMI, WC, and VAT (but not SAT) were associated with abdominal aortic calcification in age- sex-adjusted models (all p-values<0.012). However, all relations were attenuated in multivariable models (all p-values>0.23). Similar findings were observed in quartile-based analyses. In conclusion, general measures of obesity and measures of central abdominal fat are related to CAC and AAC. However, these cross-sectional associations are attenuated by cardiovascular disease risk factors, possibly because they may mediate the association between adiposity measures and subclinical cardiovascular disease.

Objective: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS).

Subjects and methods: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n  =  59), unstable angina pectoris (UAP) group (n  =  28), and stable angina pectoris (SAP) group (n  =  36).

Results: Plasma concentrations of adiponectin correlated negatively with body mass index (r  =  −0.18, p < 0.05), serum triglyceride (r  =  −0.25, p < 0.01), and fasting glucose concentrations (r  =  −0.21, p < 0.05), but correlated positively with age (r  =  0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r  =  0.35, p < 0.01), and low density lipoprotein particle size (r  =  0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) μg/ml; SAP, 11.3 (5.9) μg/ml; control 12.8 (4.3) μg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) μg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p  =  0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS.

Conclusions: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles – the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Background:

Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) may be associated with atherogenesis and plaque rupture. We evaluated the relationship between MMP-1, MMP-9, TIMP-1 and IL-6 levels and risk factors, presentation, extent and severity of atherosclerotic coronary artery disease (CAD).

Methods:

Consecutive patients who underwent coronary angiography were randomly included. The serum concentrations of MMP-1, MMP-9, TIMP-1 and IL-6 were analyzed with ELISA method in 134 patients. Participants were divided into 5 groups; stable angina pectoris (SAP; n= 34), unstable angina pectoris (USAP; n=29), non-ST elevation myocardial infarction (NSTEMI; n=16), acute ST elevation myocardial infarction (STEMI; n=25) and controls (n=30). Coronary angiographic Gensini score was calculated.

Results:

MMP-1 levels were higher in STEMI and NSTEMI groups compared with USAP, SAP and control groups (STEMI vs USAP p=0.005; STEMI vs SAP p=0.001; STEMI vs control p<0.001; NSTEMI vs USAP p=0.02; NSTEMI vs SAP p=0.027; NSTEMI vs control p<0.001). In STEMI group, MMP-9 levels were higher than USAP and control groups (p=0.002; p<0,001). TIMP-1 levels were not significantly different within all 5 groups. MMP-1 levels were found to be elevated in diabetic patients (p=0.020); whereas MMP-9 levels were higher in smokers (p=0.043). Higher MMP-1, MMP-9 and IL-6 levels were correlated with severe Left Anterior Descending artery (LAD) stenosis and higher angiographic Gensini Score (for severe LAD stenosis; r = 0.671, 0.363, 0.509 p<0.001; for Gensini score; r = 0.717, 0.371, 0.578 p<0.001).

Conclusions:

Serum levels of MMP-1, MMP-9, and IL-6 are elevated in patients with CAD; more so in acute coronary syndromes. MMP-1, MMP-9 and IL-6 are associated with more extensive and severe CAD (as represented by Gensini score).

BACKGROUND:

Rapid measuring of B-type natriuretic peptide (BNP) in the emergency departments effectively results in evaluating patients with acute cardiac attacks and has appeared to be a useful prognostic marker of cardiovascular risk. A current study came to address the association between plasma N-terminal pro BNP level and severity of coronary vessels’ defects based on Gensini score in patients with stable angina pectoris candidate for coronary angiography.

METHODS:

The study population consisted of 92 consecutive patients with appearance of stable angina and candidate for coronary angiography. All participants underwent selective left and right coronary angiography. For BNP measurement and just before the catheterization of left coronary, 5cc blood samples were drawn from coronary.

RESULTS:

With respect to the role of N terminal pro BNP for predicting severity of CAD based on Gensini scoring, linear regression analysis confirmed that plasma BNP level was a strong predictor for CAD severity (p = 0.009) in the presence of study cofounders. A significant correlation was also observed between N terminal pro BNP and left ventricular ejection fraction, so that all patients with left ventricular dysfunction (EF < 40%) had plasma N terminal pro BNP level higher than 100 pg/ml.

CONCLUSIONS:

NT-pro BNP can be a good parameter for predicting the severity of coronary vessels’ involvement besides other diagnostic tools. In all patients with left ventricular ejection fraction less than 40%, plasma NT-pro BNP level was higher than 100 pg/ml.

Background

Visceral fat deposition and its associated atherogenic complications are mediated by glucocorticoids. Cardiac visceral fat comprises mediastinal adipose tissue (MAT) and epicardial adipose tissue (EAT), and MAT is a potential biomarker of risk for obese patients.

Aim

Our objective was to evaluate the role of EAT and MAT 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and glucocorticoid receptor (GCR) expression in comparison with subcutaneous adipose tissue (SAT) in the development of coronary atherosclerosis in obese patients with coronary artery disease (CAD), and to assess their correlations with CD68 and fatty acids from these tissues.

Methods and results

Expression of 11β-HSD-1 and GCR was measured by qRT-PCR in EAT, MAT and SAT of thirty-one obese patients undergoing coronary artery bypass grafting due to CAD (obese CAD group) and sixteen obese patients without CAD undergoing heart valve surgery (controls). 11β-HSD-1 and GCR expression in MAT were found to be significantly increased in the obese CAD group compared with controls (p < 0.05). In the obese CAD group, 11β-HSD-1 and GCR mRNA levels were strongly correlated in MAT. Stearidonic acid was significantly increased in EAT and MAT of the obese CAD group and arachidonic acid was significantly expressed in MAT of the obese male CAD group (p < 0.05).

Conclusions

We report for the first time the increased expression of 11β-HSD-1 and GCR in MAT compared with EAT and SAT, and also describe the interrelated effects of stearidonic acid, HOMA-IR, plasma cortisol and GCR mRNA levels, explaining 40.2% of the variance in 11β-HSD-1 mRNA levels in MAT of obese CAD patients. These findings support the hypothesis that MAT contributes locally to the development of coronary atherosclerosis via glucocorticoid action.

Background

Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis.

Methods

The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group.

Results

EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia.

Conclusions

Increased EATV is strongly associated with coronary atherosclerosis in men.

Background

Patients with vasospastic (VA) or non vasospastic angina (NVA) without significant coronary stenosis have a reduced risk of infarction but is unclear whether or not this may be attributable to a lack of prothrombotic profile - similar to that present in patients with stable coronary artery disease (CAD).

Methods

Plasma levels of von Willebrand factor, total and free tissue factor pathway inhibitor, plasminogen activator inhibitor-1, and fibrinogen were analyzed in 15 patients with stable VA and 23 with NVA, all with vasoconstrictive response to acetylcholine although with different severity. Results were compared with those of 20 age-matched controls and 10 patients with CAD.

Results

Plasma levels of von Willebrand factor in patients with VA or NVA were higher than in controls (207 ± 62 and 203 ± 69% vs 121 ± 38%, p < 0.001) and tended to be lower than in CAD patients (264 ± 65, p = 0.145). They also presented higher total tissue factor pathway inhibitor (123 ± 18 and 111 ± 25 vs 88 ± 14, ng/ml p < 0.001) and plasminogen activator inhibitor-1 levels than controls (51 ± 30 and 52 ± 31% vs 19 ± 9 ng/ml, p < 0.001) and similar to CAD patients (134 ± 23 and 62 ± 31, respectively, ns). Moreover, free tissue factor pathway inhibitor plasma levels were lower than controls (18 ± 5 and 17 ± 5 vs 23 ± 8 ng/ml, p = 0.002) and similar to CAD patients (14 ± 5, ns). Despite this prothrombotic condition none of VA or NVA patients presented a myocardial infarction during a 9 year follow-up, an observation also reported in larger series.

Conclusions

During a stable phase of their disease, patients with VA or NVA present a prothrombotic profile that might eventually contribute to occurrence of myocardial infarction. The rarity of these events, however, may suggests that ill defined factors would protect these patients from coronary plaque rupture/fissure.

BACKGROUND:

Platelet-activating factor acetylhydrolase (PAF-AH) is a circulating enzyme that has an important role in the development of coronary artery disease (CAD). The correlations between PAF-AH and CAD are controversial. Furthermore, the differences of the enzyme levels between patients with stable and unstable CAD are not fully determined. The purpose of this study was to evaluate plasma PAF-AH levels and its association with the presence of CAD and some clinical risk factors in the patients.

METHODS:

This case-control study included 50 control subjects without CAD, 50 stable CAD patients and 50 unstable CAD patients with angiographically documented CAD. Plasma PAF-AH activity was determined by a commercial kit. The inflammatory markers, high sensitivity C-reactive protein (hsCRP) and oxidized low density lipoprotein (ox-LDL), and lipid profile were also measured. Comparisons of biochemical risk factors among all groups were performed by one way ANOVA. The association of PAF-AH activity with the presence of CAD was analyzed by multiple logistic regression.

RESULTS:

Plasma PAF-AH activity levels were higher in unstable CAD patients (0.040 ± 0.012 μmol/min/ml) than in stable CAD patients (0.032 ± 0.010 μmol/min/ml) and control subjects (0.026 ± 0.009 μmol/min/ml) (p < 0.01). Plasma PAF-AH activity was also independently associated with the presence of CAD (p< 0.01).

CONCLUSIONS:

Plasma PAF-AH activity levels were highly increased in unstable and stable CAD patients as compared to control subjects and may be a useful biomarker for CAD prediction.

We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein cholesterol (LDL-C) lowering and LDL-C-lowering plus high-density lipoprotein cholesterol (HDL-C) raising. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary endpoints were the change in mean proximal coronary diameter stenosis (Δ%Sprox) over 3 years and the frequency of the pre-defined composite of coronary artery disease (CAD) death, nonfatal myocardial infarction (MI), stroke and revascularization due to worsening ischemia. Patients with the MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with 3.5-fold increased event risk (p<0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Δ%Sprox=0.5 vs. 2.9, p<0.001) in patients with MS, and induced a small net regression in those without (Δ%Sprox=−0.3 vs. 2.0, p<0.001). Combination therapy reduced the event rate by 54% (13 vs. 28%, p=0.03) in those with MS and by 82% (3 vs. 17%, p=0.002) without. On average, each 10% reduction in LDL-C or 10% increase in HDL-C was significantly associated with 0.3 Δ%Sprox reduction. Each 10% LDL-C-lowering or 10% HDL-C-raising was associated with 11% (p=0.02) or 22% (p<0.001) event risk reduction. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL-C-lowering and HDL-C-raising therapies independently and significantly decrease coronary stenosis progression and reduce CV events.

Dyslipidemia is a common finding in patients with thyroid disease, explained by the adverse effects of thyroid hormones in almost all steps of lipid metabolism. Not only overt but also subclinical hypo- and hyperthyroidism, through different mechanisms, are associated with lipid alterations, mainly concerning total and LDL cholesterol and less often HDL cholesterol, triglycerides, lipoprotein (a), apolipoprotein A1, and apolipoprotein B. In addition to quantitative, qualitative alterations of lipids have been also reported, including atherogenic and oxidized LDL and HDL particles. In thyroid disease, dyslipidemia coexists with various metabolic abnormalities and induce insulin resistance and oxidative stress via a vice-vicious cycle. The above associations in combination with the thyroid hormone induced hemodynamic alterations, might explain the increased risk of coronary artery disease, cerebral ischemia risk, and angina pectoris in older, and possibly ischemic stroke in younger patients with overt or subclinical hyperthyroidism.

BACKGROUND

Atherosclerosis is the commonest cause of vascular disease which can involve peripheral and/or cardiac vessels. This study was conducted to evaluate the possible link between Ankle-Brachial Index (ABI) and coronary vessel involvement in patients with stable angina.

METHODS

This cross-sectional study was conducted in 2008 on 120 individuals who were hospitalized in Chamran Heart Center and underwent coronary angiography. A questionnaire was completed to obtain demographic information, history of previous heart disease and smoking. Body height and weight, as blood pressure on hand and foot were measured. The patients underwent angiography and the extent of coronary involvement (> 75%) was determined. After12-14-hour of fasting, blood sugar was obtained to measure total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The Ankle Brachial Pressure Index (ABI) was calculated as the ratio of the blood pressure in the ankles to the blood pressure in the arms. The data were analyzed by SPSS-15 using ANOVA, T-Student test, Spearman's rank correlation coefficient, and discriminant analysis.

RESULTS

Samples were 46 women (38.33%) and 74 men (61.67%) with a mean age of 55.50 ± 10.49. Mean and SD of ABI in men and women was 0.72 ± 0.20 and 0.80 ± 0.19 with no significant difference (P=0.012). The correlation between ABI and extent of coronary involvement was 0.47 (P < 0.0001). The group with lower ABI had the highest levels of coronary involvement (triple vessel, P < 0.05).

CONCLUSION

ABI had a significant relationship with the degree of coronary involvement and a significant predictive value. Therefore ABI seems to be a reliable indicator of high coronary risk.

Background and Objectives

Kawasaki disease (KD) is an acute systemic vasculitis in children which causes coronary arterial dilatation (CAD) and gallbladder distension (GBD). There is a dearth of investigating the relationship between the severity of KD and GBD with lipid profiles.

Subjects and Methods

A total of 80 patients with 'complete KD' who were diagnosed from January 2005 to May 2009 was enrolled in this study. Serum cholesterol {total, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C)}, triglyceride (TG), complete blood count, inflammation markers {erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)} were measured at the time of admission during febrile period. Echocardiography and abdominal sonogram were performed in all patients to determine CAD and gallbladder size. According to GBD, patients with KD were classified as patients with GBD and patients without GBD. Between two groups, demographic and clinical data were analyzed.

Results

The serum level of LDL-C was significantly lower in patients with GBD (p=0.03) compared with patients without GBD or febrile control. There was no significant difference in inflammatory indices between patients with GBD and patients without GBD. GBD was not significant risk factor of CAD in this study (odds ratio=2.0, 95% confidence interval=0.82-5.3, p=0.16).

Conclusion

This is the first study that highlights the relationship between the GBD and lipid metabolism in patients with KD. This study provides clinical insights about potential mechanism underpinning the relationship between the GBD and lipid metabolism.

Excess of adiposity is a risk factor for coronary artery disease, but it remains unclear if the distribution of fat is an effect modifier or if the risk is mediate by hypertension, diabetes and dyslipidemia. We investigated the association of central in addition to general obesity with coronary artery disease (CAD). A case-control study was conducted in 376 patients, aged 40 years or more, with chronic coronary disease, undergoing elective coronary angiography. Excess of adiposity was evaluated by the Body Mass Index (BMI), waist circumference, waist-hip ratio, and neck circumference. Cases (n=155) were patients referred for coronary angiography with at least 50% of coronary stenosis in at least one epicardial vessels or their branches, with diameter greater than 2.5 mm. Controls (n=221) were patients referred for coronary angiography without significant coronary disease. Odds ratios and 95%CI for significant coronary stenosis were calculated using multiple logistic regression, controlling for age, sex, years at school, smoking, hypertension, HDL-cholesterol, diabetes mellitus, and an adiposity index. There was a predominance of men and individuals older than 50 years among cases. The waist-hip ratio increased four times the chance of CAD, even after the control for confounding factors, including BMI. Neck circumference above the 90th Percentile doubled the chance of CAD, after adjustment for traditional risk factors. Neck circumference and waist-hip ratio are independent predictors of CAD, even taking into account traditional risk factors for CAD. These findings highlight the need of anthropometric assessment among patients with suspected coronary artery disease.

BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.

Background

Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pre-test probabilities of angiographically significant CAD derived from invasive coronary angiography (“Guideline Probabilities”). Reliability of Guideline Probabilities has not been investigated in patients referred to noninvasive CAD testing.

Methods and Results

We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography (CTA) Angina typicality was recorded using accepted criteria. Pre-test likelihoods of CAD with ≥50% diameter stenosis (CAD50) and ≥70% diameter stenosis (CAD70) were calculated using Guideline Probabilities. CTA images were evaluated by ≥1 expert reader to determine presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40% in men, 19% in women) and CAD70 (27% men, 11% women) when compared to other symptom categories (p<0.001 for all). Observed CAD50 and CAD70 prevalence were substantially lower than that predicted by Guideline Probabilities in the overall population (18% vs. 51% for CAD50, 10% vs. 42% for CAD70, p<0.001), driven by pronounced differences in patients with atypical angina (15% vs. 47% for CAD50, 7% vs. 37% for CAD70) and typical angina (29% vs. 86% for CAD50, 19% vs. 71% for CAD70). Marked overestimation of disease prevalence by Guideline Probabilities was found at all participating centers and across all sex and age subgroups.

Conclusion

In this multinational study of patients referred for coronary CTA, determination of pre-test likelihood of angiographically significant CAD by the invasive angiography-based Guideline Probabilities greatly overestimates the actual prevalence of disease.

Objective

picardial adipose tissue is associated with coronary artery disease, however the causal relationship between perivascular adipose tissue and local atherogenesis is unclear.

Methods and Results

Apolipoprotein E deficient (ApoE−/−) mice underwent transplantation of visceral or subcutaneous adipose tissue immediately adjacent to the right common carotid artery. Carotid arteries with fat transplants were analyzed for atherosclerosis by surface oil-red-O staining and cross-sectional analysis. Vascular function of the carotid arteries was assessed using pressure myography. Visceral fat transplants were also performed to ApoE−/− mice with neutralization of P-selectin glycoprotein ligand-1 (Psgl-1). Atherosclerosis surface area and lesion thickness were greater in mice receiving the perivascular visceral fat compared to the subcutaneous fat. Mice with visceral fat transplants also displayed more complicated atherosclerotic lesions with evidence of atherothrombosis. Serum Mcp-1 was higher in mice receiving visceral fat transplants compared to subcutaneous transplants. Visceral fat transplantation also caused impaired endothelial-dependent relaxation of the carotid artery. Psgl-1 deficiency or neutralization of Psgl-1 with an anti-Psgl-1 antibody was protective against perivascular visceral adipose tissue-induced atherosclerosis and was associated with reduced Mcp-1 levels.

Conclusions

Perivascular visceral fat leads to endothelial dysfunction and accelerated atherosclerosis. This proatherogenic effect of perivascular adipose tissue is blocked by neutralization of Psgl-1.

Background

It is still unknown whether increased cardiac adiposity is related to the risk factors of coronary artery disease (CAD). We measured epicaridal adopose tissue (EAT) and mediastinal adipose tissue (MAT) using echocardiography and examined their correlations with CAD and serum adiponectin.

Methods

One hundred fifty three patients who underwent elective coronary angiography for chest pain were measured cardiac adiposity by transthoracic echocardiography. The correlations of cardiac adipose tissue with the presence and severity of CAD and the serum adiponectin level were examined.

Results

EAT was thicker in patients with CAD (1.8±1.4 vs. 3.8±1.9 mm, p<0.001), but MAT was not different according to the presence of CAD (2.9±2.8 vs. 3.5±2.5 mm, p=0.121). EAT showed a significant positive correlation with age (r=0.225, p=0.005), homocystein (r=0.289, p=0.001), fasting glucose (r=0.167, p=0.042), and fibrinogen (r=0.218, p=0.009), and a significant negative correlation with serum adiponectin (r=-0.194, p=0.016). EAT thickness (OR 11.53, 95% CI; 3.61-36.84, p<0.001) and low serum adiponectin (OR 2.88, 95% CI; 1.02-8.15, p=0.046) were independent predictors of obstructive CAD. However, MAT thickness was not associated with CAD.

Conclusion

EAT was associated with the severity and risk factors of CAD and correlated with serum adiponectin level. In contrast with EAT, MAT was not associated with CAD and adiponectin.

Background

Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in142 normolipidemic subjects undergoing coronary angiography.

Methods

Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography.

Results

Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concntration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02).

Conclusion

Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.

Eighty-five consecutive patients with hypertrophic cardiomyopathy underwent hemodynamic evaluation and coronary arteriography to determine, in each case, the incidence and importance of coronary artery disease (CAD). Sixteen patients (19%) had >60% narrowing of the luminal diameter of one or more coronary arteries.

Our findings revealed that patients with CAD were significantly older (mean, 64 years) than patients without CAD (mean, 42 years) and had a higher incidence of angina pectoris (81% versus 44%). Left ventricular end-diastolic pressures were lower in patients with CAD (mean, 17 mm Hg) than in those without CAD (mean, 23 mm Hg). The electrocardiographic findings were similar in both groups. There was no operative mortality in either group.

In five patients with severe stenosis of the left anterior descending coronary artery (>90%), no collaterals to that artery were seen. In two, filling of the narrowed artery appeared slower than usual.

Our study indicates that in patients older than 45 years of age with hypertrophic cardiomyopathy, the incidence of CAD is significantly higher, and warrants coronary arteriography prior to consideration for cardiac surgery.

In this study, patients with hypertrophic cardiomyopathy and CAD who underwent corrective surgery for hypertrophic cardiomyopathy concomitantly with coronary artery bypass surgery have had low operative and long-term mortality with long-lasting symptomatic improvement.

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.

Author Summary

The WHO predicts that coronary artery disease (CAD) will become the leading cause of death worldwide in 2010. Currently, major research efforts are focused on understanding the genetics of CAD through multi-center, genome-wide association studies of tens of thousands of patients and controls. Such studies can identify common variants of general importance throughout the entire population, which are likely relatively few. The number of rare genetic variants and variants that act in the context of environmental risk factors for CAD is probably much higher. We performed whole-genome expression analyses in several organs to identify functionally associated genes important for CAD development. We found an atherosclerosis module (A-module) consisting of 128 genes, enriched with genetic risk for CAD, involving transendothelial migration of leukocytes (TEML) and LIM domain binding 2 (LDB2) as its high-hierarchy regulator. Our study design represents a novel way of understanding the molecular underpinnings of CAD, focusing on genome-wide expression sensing both environmental and genetic influences. Investigating the relative enrichment of genetic CAD risk in functional groups (modules and networks) is an alternative approach to extract additional relevant information from genome-wide association studies. The A-module and LDB2 are attractive targets for treatments to modulate TEML and atherosclerosis development.

Abdominal obesity has been associated with liver fat storage. However, the relationships between other body composition depots and metabolic syndrome features with hepatic fat are still unclear. We examined abdominal and thigh adipose tissue (AT) compartments associations with liver fat in 140 overweight and obese premenopausal Caucasian women. Blood lipids and, proinflammatory and atherothrombotic markers associations with hepatic fat were also analyzed. A larger visceral AT (VAT) was related with liver fat (P < 0.05). Contrarily, thigh subfascial AT was inversely related to liver fat (P < 0.05). Increased fasting insulin, triglycerides, PAI-1 concentrations, and a higher total-cholesterol/HDL-cholesterol ratio were also associated with hepatic fat, even after adjustment for VAT (P < 0.05). Thigh subfascial adiposity was inversely associated with liver fat, suggesting a potential preventive role against ectopic fat storage in overweight and obese women. These results reinforce the contribution of an abdominal obesity phenotype associated with a diabetogenic and atherothrombotic profile to liver lipotoxicity.

Background and Objectives

Thrombospondin-1 (TSP-1) is associated with atherosclerosis in animals with diabetes mellitus (DM). But, no study has investigated the role of TSP-1 in human atherosclerosis. This study investigated the relationship among plasma TSP-1 concentration, DM, and coronary artery disease (CAD).

Subjects and Methods

The study involved 374 consecutive subjects with suspected CAD, who had undergone coronary angiography to evaluate effort angina. Patients were divided into four groups as follows: DM(-) and CAD(-), DM(-) and CAD(+), DM(+) and CAD(-), and DM (+) and CAD(+).

Results

We found that plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) (n=103) than those in other patients (n=271) (p<0.01). A multivariate analysis showed that male gender {odds ratio (OR), 2.728; 95% confidence interval (CI), 1.035-7.187}, high density lipoprotein-cholesterol (OR, 0.925; 95% CI, 0.874-0.980), glycated hemoglobin (OR, 1.373; 95% CI, 1.037-1.817), and plasma TSP-1 (OR, 1.004; 95% CI, 1.000-1.008) levels were independently associated with the presence of CAD in patients with DM.

Conclusion

Plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) than those in other patients, and plasma TSP-1 levels were independently associated with the presence of CAD in patients with DM. These findings show a possible link between human plasma TSP-1 concentration and CAD in patients with DM.