Association of low serum level of secreted frizzled-related protein 5 (SFRP5) with the presence and severity of coronary artery disease

Background: Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine that excreted by adipose tissue and functions to modulate metabolic and inflammatory dysregulations. The exact contribution of SFRP5 toward coronary artery disease (CAD) is largely unclear. Objectives: In the current study, the potential role of SFRP5, by particular focusing on its anti-inflammatory effects, was sought in CAD. Patients and Methods: Serum levels of SFRP5 and the inflammatory biomarkers, oxidized low-density lipoprotein (Ox-LDL), and high-sensitivity C-reactive protein (hsCRP), were measured in 40 CAD patients and 40 controls who were identified based on coronary angiography examinations. The status of CAD severity (in accord with Gensini score) and traditional CAD risk factors were also determined. Association of SFRP5 with Ox-LDL, hsCRP, CAD severity, and traditional CAD risk factors was analyzed. Results: Serum SFRP5 level in CAD patients was significantly decreased compared to controls (28.60 ng/mL [25.67–34.58] vs. 39.92 ng/mL [32.82-49.91], P = 0.000). The correlation of serum SFRP5 level with hsCRP, Ox-LDL, body mass index, and Gensini score was reveal to be significant and negative (P

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.

This study investigated the biomarker effect of soluble lectin-like oxidised low-density lipoprotein (sLOX-1) levels for the evaluation of stable and unstable coronary heart disease, correlating it with aging. This case-control study was conducted at the Cardiology Department of Xiangya Hospital between June 2015 and September 2018. Stable coronary artery disease (CAD) patients were confirmed by an invasive coronary angiogram, and American College of Cardiology as well as European Cardiology Society clinical protocols were used for the diagnosis of unstable CAD subjects. Plasma sLOX-1 levels were determined from 226 stable CAD patients, 138 unstable CAD subjects and 75 healthy participants by enzyme-linked immunosorbent assay. Plasma sLOX-1 expressions were significantly elevated in stable CAD patients (4.5-fold) and unstable CAD patients (5.8-fold) above that of volunteer healthy participants. Moreover, between the stable and unstable patient groups, sLOX-1 concentrations were also statistically significantly different (p < 0.001). Levels of plasma sLOX-1 in the healthy female (30-60 years), and stable and unstable CAD female subjects (61-84 years) were markedly elevated compared with healthy male (30-60 years), as well as stable and unstable CAD male patients (61-84 years) (p < 0.001). Besides, in the female unstable CAD (61-84 years) subjects, circulatory sLOX-1 expressions were much higher than in the younger female unstable CAD (30-60 years) patients (p < 0.001). The stable CAD patients were clearly differentiated from healthy subjects with a high sensitivity of the area under the curve (AUC = 0.895). Unstable CAD patients and healthy subjects were also markedly different with a high sensitivity, as shown by AUC (0.902). Stable and unstable CAD subjects were differentiated with an AUC of 0.867. Elevated plasma sLOX-1 levels could be regarded as a novel biomarker for detecting CAD patients and there was a significant association with gender and aging.

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. Serum soluble lectin-like oxidized low-density lipoprotein receptor-1(sLOX-1) is associated with coronary artery disease (CAD) and metabolic disorders. We sought to assess whether serum sLOX-1 levels are correlated with the presence and severity of CAD in patients with metabolic syndrome (MetS) undergoing coronary angiography. Serum sLOX-1 levels were measured in 112 consecutive patients with MetS, undergoing coronary angiography for the evaluation of CAD. The severity of CAD was assessed by angiographic Gensini score system. Serum sLOX-1 levels were significantly higher in MetS patients with CAD (n=69) than in those without CAD (n=43) (0.925 [range 0.137 to 1.432] ng/ml vs. 0.207 [range 0.063 to 0.774] ng/ml, P < 0.01). Multivariate logistic regression analysis revealed that serum sLOX-1 level was independently associated with the presence of CAD (odds ratio 2.489, 95% confidence interval 1.290-4.802; P < 0.01). Serum sLOX-1 levels were positively correlated with the Gensini score (ρ: 0.394, P < 0.01) after adjusting for other clinical characteristics. High sLOX-1 levels are associated with the presence and severity of CAD in patients with MetS. The measurement of serum sLOX-1may be potentially useful in predicting the presence and severity of CAD in patients with MetS.

Background: Lipid disorder was one of the major risk factors for coronary artery disease (CAD), especially in postmenopausal women, whose lipid profile significantly changed during the transition period to menopause. The aim of the present study was to examine whether plasma lipoprotein(a) [Lp(a)] was a biomarker for predicting the presence and severity of CAD in postmenopausal women. Methods: A total of 783 postmenopausal women who had their first angina-like chest pain were enrolled and classified into two groups according to the results of coronary angiography: CAD group (n = 309) and age-matched non-CAD group (n = 309). Patients with CAD were further divided into the three groups based on Gensini score (GS). The relationships of plasma Lp(a) levels to the presence and severity of CAD were evaluated, and the predictive value of Lp(a) for CAD was also examined. Results: CAD group had higher Lp(a) levels when compared to non-CAD ones (p < 0.001). The multivariate logistic regression analysis suggested that Lp(a) was an independent predictor for the presence of CAD (p < 0.001). Plasma levels of Lp(a) were significantly related to GS (p < 0.001). In addition, plasma Lp(a) level was significantly elevated according to the tertiles of GS (p = 0.001) and was independently associated with high GS (p < 0.001). In receiver-operating characteristic analysis for predicting the presence of CAD in postmenopausal women, Lp(a) was found to have the area under the curve of 0.703, with an optimal cutoff value of 255.69 mg/L. Conclusions: Lp(a) is an independent risk factor for predicting the presence and the severity of new-onset CAD in postmenopausal women, suggesting that Lp(a) may be a lipid target for prevention and treatment in such patients.

Blood pressure (BP)-lowering treatment should be aimed at achieving intensive BP control. Coronary computed tomography angiography (CCTA) has become more widely available and enables the accurate noninvasive assessment of coronary artery stenosis for screening. The presence and severity of coronary artery disease (CAD) in patients who achieved intensive BP control at the time of CCTA were compared to those in patients without hypertension (HTN). Nine hundred eighty-five consecutive subjects who were clinically suspected of having CAD or who had at least one cardiac risk factor underwent CCTA. The patients were divided into four groups: patients without HTN (non-HTN group), hypertensive patients who underwent intensive BP lowering (intensive group, <130/80 mmHg), patients who underwent standard BP lowering (standard group, 130-139/80-89 mmHg) and patients with uncontrolled BP (uncontrolled group, >140/90 mmHg). Interestingly, %CAD in the Intensive group was significantly higher than that in patients without HTN. The Intensive group was older and had a higher body mass index, more significantly stenosed coronary vessels, lower levels of high-density lipoprotein cholesterol in the blood, and higher rates of dyslipidemia, diabetes, and anti-dyslipidemia and anti-diabetic medication use than the non-HTN group. The presence of CAD in the Intensive group was independently associated with age, male and smoking, whereas the presence of CAD in the non-HTN group was associated with age, male and family history. Finally, predictors of the number of VDs in the non-HTN and intensive BP-lowering groups were age, male, DL, and intensive BP lowering. In conclusion, these results suggest that hypertensive patients need more rigorous management of other coronary risk factors, despite receiving intensive BP-lowering treatment.

Background: The impact of chronic kidney disease (CKD) on the association of cardiovascular (CV) and renal biomarkers with the presence and severity of coronary artery disease (CAD) in patients with suspected CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 2324 patients with suspected but no history of CAD undergoing elective coronary angiography, we assessed the impact of CKD on the association of CV and renal biomarkers with the presence and severity of CAD. Heparin-free fasting serum levels of soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), VEGF, placental growth factor (PlGF), N-terminal pro-brain natriuretic peptide (NT-proBNP), contemporary sensitive cardiac troponin-I (cTnI), high-sensitivity CRP (hs-CRP), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured in 887 CKD and 1437 non-CKD patients enrolled in the EXCEED-J study. The severity of CAD was quantified using the Gensini score. Results: The mean age (standard deviation) of the patients was 69.8 (10.8) years; 65.6% were men. Serum levels of all biomarkers except PlGF were significantly higher in CKD than in non-CKD patients. In the entire patient cohort, only natural log-transformed (Ln-) cTnI was significantly associated with CAD, multi-vessel or left main trunk disease (MVD/LMTD), and Ln-Gensini score after adjustment for potential confounders. These associations were still significant in non-CKD, but not in CKD: Ln-cTnI was significantly associated with MVD/LMTD and Ln-Gensini score, but not with CAD. Stepwise regression analyses including potential confounders and all biomarkers revealed that Ln-cTnI was independently associated with CAD, MVD/LMTD, and Ln-Gensini score in the entire cohort and in non-CKD, but not in CKD: Ln-cTnI was independently associated with MVD/LMTD and Ln-Gensini score, but not with CAD. No other biomarker exhibited an independent association with CAD, MVD/LMTD, or Ln-Gensini score in the entire cohort, in non-CKD, or in CKD. Conclusions: Among CV and renal biomarkers measured in this study, only Ln-cTnI was independently associated with the presence and severity of CAD in patients with suspected CAD. These associations were attenuated in patients with CKD.

Differential associations of renal function with coronary and peripheral atherosclerosis

Association of growth differential factor-15, hs-cardiac troponin T and N-terminal pro-brain natriuretic peptide with coronary artery disease in patients undergoing elective coronary angiography

The predictability of brachial-ankle pulse wave velocity (baPWV) for the presence and severity of coronary artery disease (CAD) was investigated by measuring baPWV in 501 subjects scheduled for coronary angiography. Severity of CAD was measured using modified Gensini stenosis score (GSS) and classified as a vessel disease score (VDS) of 0–3. The presence of CAD was defined as diameter stenosis > 50%. Subjects were grouped in tertile by level of baPWV (<14, 14–17, >17 m/s). Subjects with CAD showed higher mean age, prevalence of men and diabetes, and systolic blood pressure. The prevalence of hypertension, use of antihypertensive medications and use of statin was not different. Subjects with CAD had higher baPWV than subjects without CAD (16.70 ± 3.46 versus 15.21 ± 3.19 m/s, p < 0.001). Multiple linear regression analysis showed significant correlation of baPWV and modified GSS (p = 0.0337). ANCOVA adjusted with age, gender, body mass index, presence of hypertension or diabetes, status of smoking, use of antihypertensive medications and risk of hypercholesterolemia showed a statistically significant association of baPWV with VDS (p < 0.0001). Highest tertile of baPWV had a statistically significant effect on the severity of CAD from an ANCOVA model. The predictive power of highest tertile of baPWV for the presence of CAD was 3.600 [95% confidence interval (CI) 1.884–6.881, p < 0.0001]. It is concluded that increased baPWV is a reliable predictor of the presence and severity of CAD, suggesting that baPWV > 17 m/s may be a threshold value for the presence and severity of CAD.

ObjectiveTo study whether free triiodothyronine (FT3) within normal range has effects on the presence and severity of coronary artery disease (CAD) in different gender and age groups.MethodsA total of 4206 euthyroid patients were consecutively enrolled and divided into CAD group (n = 3306) and non-CAD group (n = 900). All patients underwent coronary angiography (CAG). Gensini score (GS) was used to determine the severity of coronary artery stenosis. Severe CAD was defined as GS > 32 and mild CAD was defined as GS ≤ 32. Logistic regression analysis and linear regression analysis were conducted to determine the association of FT3 with CAD in patients with different gender and ages.ResultsConcentration of FT3 was lower in patients with CAD than that in angiography-normal control group (P < 0.05). In addition, concentration of FT3 was lower in severe CAD than that in mild CAD. After adjusting for traditional cardiovascular risk factors and potential confounders, FT3 was negatively correlated with the presence of CAD, but not in the old patients (> 65 years old). Multivariable linear regression analysis showed that FT3 was negatively associated with GS in male and young patients with stable CAD, but not in the old patients.ConclusionsLow FT3 within normal range was negatively associated with the presence and severity of CAD in young patients, but not in the old ones. Further studies are needed to confirm our findings.

Fasting serum total bile acid level is associated with coronary artery disease, myocardial infarction and severity of coronary lesions

Background and Objectives: Chronic kidney disease (CKD) increases the risk of coronary artery disease (CAD), and vitamin D deficiency—particularly reduced levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the biologically active form of vitamin D that declines early in CKD due to impaired renal conversion—may be a contributing factor. This study aimed to assess the relationship between 1,25(OH)2D levels and the presence and severity of CAD in CKD patients. Materials and Methods: We retrospectively analyzed 398 non-dialysis CKD patients (eGFR < 60 mL/min/1.73 m2) who underwent elective coronary angiography. Serum 1,25(OH)2D and 25(OH)D levels were measured, and CAD severity was assessed using the Gensini score. Results: Lower 1,25(OH)2D levels were independently associated with both the presence and se-verity of CAD. Logistic regression revealed that each 1 pg/mL increase in 1,25(OH)2D was linked to an 11% reduction in odds of significant CAD (OR: 0.89; 95% CI: 0.86–0.93; p < 0.001). In contrast, 25(OH)D was not significantly related to CAD. Linear regression showed an inverse correlation between 1,25(OH)2D and Gensini scores (β = −0.329, p < 0.001), indicating reduced disease severity with higher vitamin D levels. Subgroup analyses confirmed consistent associations across age, sex, diabetes, hypertension, and LDL-cholesterol categories. ROC analysis demonstrated that 1,25(OH)2D alone had good predictive ability for CAD (AUC = 0.818), which improved to 0.925 when combined with traditional risk factors. The optimal cutoff for 1,25(OH)2D was ≤16.6 pg/mL, yielding 73.3% sensitivity and 83.5% specificity. Conclusions: Serum 1,25(OH)2D is an independent predictor of both the presence and extent of CAD in CKD patients and may serve as a valuable non-traditional biomarker for cardiovascular risk assessment.

BackgroundPreβ1-high-density lipoprotein (preβ1-HDL), plays an important role in reverse cholesterol transport and exhibits potent risk for coronary artery disease (CAD). However, the association of plasma preβ1-HDL and cholesterol ester transfer protein (CETP) levels in CAD patients and the relationship of preβ1-HDL with extent of CAD are debatable.MethodsPreβ1-HDL and CETP levels were measured by enzymed-linked immunosorbent assay (ELISAs) in 88 acute coronary syndromes (ACS), 79 stable coronary artery disease (SCAD) patients and 85 control subjects. The correlation analyses, multiple linear regression analyses and logistic regression analyses were performed, respectively.ResultsThe preβ1-HDL and CETP levels in ACS patients were significantly higher than those in SCAD patients and both of them were higher than controls’. Preβ1-HDL levels were positively associated with CETP (R = 0.348, P = 0.000), the diameter of stenosis (R = 0.253, P = 0.005), the number of vessel disease (R = 0.274, P = 0.002) and Gensini score (R = 0.227, P = 0.009) in CAD patients. Stepwise multiple linear regression analyses showed that CETP was one of the determinants of preβ1-HDL levels. Logistic regression analysis revealed that elevated preβ1-HDL and CETP were potential risk factors for both ACS and SCAD.ConclusionThe elevated preβ1-HDL levels may change with CETP concentrations in CAD patients and were related to the presence and severity of CAD.

IntroductionSoluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.Methods and ResultsWe measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C‐statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR.ConclusionElevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.