Aortic stiffness is an independent predictor of left ventricular function in patients with coronary heart disease

Although aortic stiffness plays an important role in patients with coronary artery disease (CAD), the influence of aortic stiffness on left ventricular systolic function has not yet been fully evaluated. In the present study, we measured brachial-ankle pulse wave velocity (baPWV), which is a new index of aortic stiffness, in patients with CAD (CAD group, n = 170, 67 +/- 9 years old) and without CAD (non-CAD group, n = 81, 63 +/- 8 years old), and evaluated the relationship between baPWV and left ventricular systolic function in patients with CAD. baPWV in the CAD group was significantly higher than that in the non-CAD group (1,794 +/- 350 vs. 1,469 +/- 292 cm/s, p < 0.05), although both systolic and diastolic blood pressure were comparable between the two groups. In the CAD group, the baPWV was higher in patients with three-vessel disease than that in patients with one-vessel disease (1,885 +/- 542 vs. 1,720 +/- 373 cm/s, p < 0.05). In the CAD group, multivariate analysis demonstrated that baPWV and pulse pressure independently correlated with left ventricular ejection fraction (LVEF). In conclusion, in patients with CAD, baPWV, which is a simple marker of aortic stiffness, increases with CAD severity and correlates with left ventricular systolic function independent of CAD severity.     

血浆氧化低密度脂蛋白水平是冠心病严重程度的独立预报因素

目的研究血浆氧化低密度脂蛋白（OxLDL）水平与冠心病严重程度的关系。方法134例怀疑为冠心病的住院患者,进行选择性冠状动脉造影。根据冠脉造影结果,将患者分为冠心病组（113例,至少有1支冠脉狭窄≥50%）和对照组（21例,所有冠脉分支狭窄均<50%）。冠心病组按照冠脉病变支数进一步分为4个亚组（1支病变26例,2支病变26例,3支病变53例,4支病变8例）;按照发病症状分为稳定型心绞痛组（51例）、不稳定型心绞痛组（22例）和急性心肌梗死组（40例）。血浆OxLDL水平采用ELISA试剂盒检测。其他冠心病危险因素如年龄、性别、体质量指数、血脂等数据也一并收集。结果在冠心病组和对照组之间,除了高血压病史有显著升高外（46%vs19%,P<0.05）,其他指标没有显著差别。冠心病患者血浆OxLDL水平显著高于对照组（1.15±0.32）μkat/m lvs（0.68±0.30）μkat/m l,P<0.01)。14支病变冠心病患者,其血浆OxLDL含量均显著高于对照组（1.10±0.32）μkat/m l、（1.12±0.27）μkat/m l、（1.17±0.32）μkat/m l和（1.33±0.37）μkat/m lvs（0.68±0.30）μkat/m l,P<0.01);但不同支数病变患者亚组间无显著性差异。稳定型心绞痛、不稳定型心绞痛和急性心肌梗死患者血浆OxLDL含量均显著高于对照组（1.13±0.30）μkat/m l,（1.23±0.33）μkat/m l和（1.15±0.32）μkat/m lvs（0.68±0.30）μkat/m l,P<0.01);但是各分组之间无显著性差异。以血浆OxLDL水平为因变量进行多元回归分析,发现冠脉病变支数是血浆OxLDL水平升高的独立危险因素（P<0.01）。结论血浆OxLDL水平是冠心病严重程度独立预报因素。     

The stroke volume/pulse pressure ratio predicts coronary heart disease mortality in a population of elderly men

BACKGROUND: The stroke volume to pulse pressure ratio (SV/PP), a measure of total arterial compliance, predicts adverse cardiovascular events in hypertensive subjects. The relations to cardiovascular risk factors and its predictive capacity in the general population are not known. METHOD AND RESULTS: In 1970-73, all 50-year-old men living in Uppsala County, Sweden, were invited to a health survey assessing cardiovascular risk factors. At a reinvestigation 20 years later, 470 subjects underwent an echocardiographic examination, hyperinsulinaemic euglycaemic clamp, oral glucose tolerance test and measurements of blood pressure and lipids. They were thereafter followed for a median of 7.2 years. Serum triglycerides and post-load glucose and insulin levels at age 50 were predictors of SV/PP ratio measured 20 years later (P < 0.05-0.001). At age 70, SV/PP was related to serum non-esterified fatty acids, post-load glucose and insulin levels and insulin sensitivity (P < 0.05-0.001). SV/PP was reduced in subjects with concentric left ventricular hypertrophy (LVH, P < 0.01), and in subjects with a low E-wave to A-wave (E/A) ratio (P < 0.001). The SV/PP ratio predicted mortality from coronary heart disease [hazard ratio 0.54, 95% confidence interval 0.30-0.97 for a one standard deviation (1SD) increase in ln(SV/PP)] independently of left ventricular mass and other major cardiovascular risk factors. Pulse pressure or total peripheral resistance were not significant predictors for future mortality from coronary heart disease. CONCLUSION: The SV/PP ratio was related to main components of the insulin resistance syndrome, concentric LVH and a low E/A ratio. Furthermore, the SV/PP ratio was an independent predictor of mortality from coronary heart disease in a community-based sample of men aged 70.     

High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men.

Pulse wave velocity (PWV) is an index of arterial stiffness, and a simple device for measuring brachial-ankle PWV (baPWV) has recently been developed. However, the clinical application of baPWV in patients with coronary artery disease (CAD) remains to be fully evaluated. This cross-sectional study was conducted to evaluate whether a higher baPWV predicts the presence of CAD. The baPWV was measured in 123 patients (77 males, 46 females; 63.5+/-11.8 years) who were undergoing coronary angiography. CAD was defined as >50% diameter stenosis. Hemodynamic data and cardiovascular risk factors were examined according to the presence or absence of CAD. Patients with CAD were significantly older across both sexes. The presence of hypertension and chest pain, but not baPWV, was correlated with CAD in females. The baPWV, and the presence of diabetes, hyperlipidemia, and chest pain were related to the presence of CAD in males. Multivariate logistic regression analysis in male patients showed that baPWV, diabetes, hyperlipidemia, and chest pain were independent risk factors for the presence of CAD. Furthermore, high baPWV in males with or without chest pain had a positive predictive value of 81.8% and 71.7% for the presence of CAD, respectively. In conclusion, high baPWV was shown to be a good independent predictor for the presence of CAD in men.     

High fibrinogen level is an independent predictor of presence and extent of coronary artery disease among Italian population

Few reports have so far investigated the relationship between fibrinogen levels and the extent of coronary artery disease (CAD) as evaluated by coronary angiography, that is therefore the aim of the current study. We measured fibrinogen in 2,121 consecutive patients undergoing coronary angiography. Patients were divided in 5 groups based on quintiles of fibrinogen levels. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured carotid intima-media thickness (CIMT) in a subgroup of 359 patients. Patients with elevated fibrinogen were older (P = 0.038), with larger prevalence of diabetes (P = 0.027), female gender (P < 0.0001), hypertension (P < 0.001), chronic renal failure (P < 0.0001), previous CVA (P = 0.036), less often with family history of CAD (P = 0.019) and previous PCI (P < 0.0001), more often presenting with ACS (P < 0.0001), more often on nitrates (P < 0.0001), clopidogrel (P = 0.009) and diuretics (P < 0.0001). Fibrinogen levels were linearly associated with baseline glycaemia (P < 0.017), WBC count (P < 0.0001), creatinine (P < 0.0001), and Platelet count (P < 0.0001) but inversely associated with RBC count (P < 0.0001). Fibrinogen levels were associated with CAD (P = 0.001), especially for extremely high levels (5th percentile, P < 0.0001). At multivariate analysis, after correction for baseline confounding factors, high fibrinogen level (5th percentile) was still associated with the prevalence of CAD (P = 0.034). Furthermore, fibrinogen levels were related with maximal CIMT (r = 0.12; P = 0.01), with larger prevalence of carotid plaques in patients with higher fibrinogen levels (5th quintile) as compared to remaining patients (P = 0.046). This study showed that high fibrinogen level is significantly associated with CAD and carotid atherosclerosis.     

Lipoprotein(a) was an independent predictor for major coronary events in treated hypertensive men

BACKGROUND AND HYPOTHESIS: Lipoprotein(a) may play a part in the development of coronary heart disease. The purpose of this prospective study was to evaluate lipoprotein(a) as a predictor of major coronary events (fatal and nonfatal myocardial infarction and sudden death). METHODS: This was a prospective study of 118 men, aged 56 to 77 years, with treated hypertension and at least one additional cardiovascular risk factor (hypercholesterolemia, diabetes mellitus, or smoking) were included in the study. Lipoprotein(a) was measured at entry and major coronary events were followed during follow-up. RESULTS: The mean observation time was 3.0 years. Fourteen patients had a major coronary event during the follow-up period. Subjects with coronary heart disease (previous myocardial infarction, angina pectoris, or major electrocardiographic changes) at entry (n = 27) had significantly higher lipoprotein(a) levels than subjects without (n = 91) known coronary heart disease (p < 0.05). Lipoprotein(a) was a significant predictor for major coronary events (p = 0.033). Furthermore, when coronary disease at entry was included into the Cox regression analysis, lipoprotein(a) was an independent predictor for major coronary events (p = 0.044). CONCLUSIONS: Among treated hypertensive men, lipoprotein(a) was an independent predictor of major coronary events.     

Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men

Most previous studies of associations between insulin sensitivity and common carotid artery (CCA) atherosclerosis have been conducted in small samples, have not used direct measurement of insulin sensitivity, and have yielded inconclusive results. We investigated associations of CCA intima-media thickness (IMT) and diameter (CCA-D) measured by B-mode ultrasound and insulin sensitivity measured by the euglycemic hyperinsulinemic clamp test together with risk factors of the insulin resistance syndrome in a community-based sample of 493 elderly men. The clamp glucose disposal rate was an independent predictor of CCA-IMT in multivariate models adjusting for blood pressure, smoking, serum cholesterol, and body mass index (1% decrease in CCA-IMT for a 1 unit increase in glucose disposal rate, P=0.009). Glucose disposal rate was significantly related to CCA-D in univariate (r=-0.11, P=0.02) but not in multivariate models. In conclusion, this study is the first to establish impaired insulin sensitivity, measured by the euglycemic hyperinsulinemic clamp test, as an independent predictor of CCA-IMT in a population-based sample of elderly men.     

Delayed intravascular catabolism of chylomicron-like emulsions is an independent predictor of coronary artery disease

The atherogenic role of a delayed intravascular catabolism of chylomicrons has been suggested by univariate analysis of case-control studies. However, it is not established whether this association is caused by a direct atherogenic effect of these lipoproteins or results from the presence of concurrent and metabolically-related coronary artery disease (CAD) risk factors. In this study, the plasma kinetics of a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate (CE) and 3H-triolein (TG) was determined in 93 subjects with or without angiographically-defined CAD. As compared with controls and even after adjustment for body mass index (BMI), LDL- and HDL-cholesterol, and the presence of traditional risk factors, CAD patients had 45% smaller fractional clearance rate (FCR) of TG, 41% smaller FCR-CE and 19% smaller dilapidation index (DI; P < 0.05). Among CAD patients, those with highest angiographic score had 66% smaller FCR-TG (P = 0.007), 50% smaller FCR-CE (P = 0.01) and 27% smaller DI (P = 0.004). In a multivariate logistic regression analysis, FCR-CE (P < 0.0001) and DI (P = 0.001) were the only independent predictors for the presence of CAD. In conclusion, we presently show that the rate of lipolysis and removal from the circulation of chylomicron-like emulsions constitutes an independent predictor of CAD and a marker of CAD severity.     

Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men

CONTEXT: Cross-sectional and nested case-control studies indicate a relationship between adiponectin, obesity, and coronary heart disease (CHD). OBJECTIVE: Our objective was to investigate whether adiponectin could predict CHD in a population-based cohort of elderly men. DESIGN AND SETTING: From 1991-1995 a baseline investigation was carried out in 832 healthy men aged 70 yr in the Uppsala Longitudinal Study of Adult Men (ULSAM study). They were followed up to 10.4 yr using Swedish national registry data. The baseline investigation included anthropometry, blood pressure, smoking, serum lipids, a euglycemic insulin clamp, and fasting serum adiponectin. MAIN OUTCOME MEASURES: Main outcome measures were defined as death or first-time hospitalization for CHD (n = 116), recorded in the Cause of Death Registry or in the Hospital-Discharge Registry of the National Board of Health and Welfare, Sweden. Associations were analyzed using Cox's proportional hazards regression, presented as hazard ratios (HR) with 95% confidence intervals (CI) for 1 sd increase in the predictor variable. RESULTS: In a multivariable analysis including total cholesterol (HR, 1.24; CI, 1.02-1.50), high-density lipoprotein cholesterol (HR, 0.72; CI, 0.58-0.89), smoking (HR, 1.39; CI, 0.91-2.14), and systolic blood pressure (HR, 1.26; CI, 1.05-1.52), serum adiponectin was associated with lower risk for CHD (HR, 0.81; CI, 0.66-0.99). The association was independent of BMI and remained significant after adjustment for insulin sensitivity index. CONCLUSIONS: In this population-based cohort of healthy men, elevated serum levels of adiponectin were associated with a lower risk for CHD. Importantly, the association between adiponectin and CHD was independent of other well-known risk factors.     

Serum uric acid is not an independent risk factor for coronary heart disease

Many large epidemiologic studies have confirmed a positive association between raised serum uric acid and risk of coronary heart disease or cardiovascular disease, both in the general population and among hypertensive patients. There is much controversy concerning the role of uric acid as an independent risk factor in the development of coronary heart disease because serum uric acid is related to many of the established etiologic risk factors for cardiovascular disease that could confound the observed association. This review finds little support for an independent causal role for serum uric acid in the development of coronary heart disease.     

Circulating oxidized low-density lipoprotein is an independent predictor for cardiac event in patients with coronary artery disease

Oxidized low-density lipoprotein (oxLDL) plays a crucial role in the development of atherosclerosis, however, the predictive value of circulating oxLDL for cardiac events (CE) in patients with coronary artery disease (CAD) has remained poorly understood. We prospectively studied 238 consecutive patients with documented CAD for up to 52 months until the occurrence of one of the following cardiac events: cardiac death, nonfatal myocardial infarction (MI), and refractory angina requiring revascularization. The plasma levels of oxLDL were measured by an enzyme-linked immunosorbent assay (ELISA) using the monoclonal antibody, DLH3. The levels of circulating oxLDL were significantly higher in patients with CE than in patients without CE (median 20.3 U/ml versus 17.6 U/ml, P = 0.002). Multivariate Cox models showed that higher level of oxLDL was an independent predictor of developing CE. The adjusted hazard ratios for CE were 3.15 (95% CI 1.47-6.76, P = 0.003) times higher in patients with the highest quartile of oxLDL levels and 1.88 (95% CI 0.90-3.95, P = 0.09) times higher in patients with the third quartile than in those within the lowest quartile. Thus, measurement of circulating oxLDL may be helpful in the assessment of future CE in patients with CAD.     

Soluble VEGF/sFLt1 ratio is an independent predictor of AML patient out come

Angiogenesis is the formation of new blood vessels and is controlled by a balance between positive and negative angiogenic regulatory factors. Soluble vascular endothelial growth factor receptors 1,2 (Flt-1, KDR) are the negative counterpoint to the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulator in human angiogenesis. In the present work, we tested the differential prognostic relevance of soluble vascular endothelial growth factor (VEGF), their receptors 1 (Flt-1), 2 (KDR), and the ratio between sVEGF/sFlt-1 in 43 patients with acute myeloid leukemia (AML). sVEGF and its soluble receptors were assessed using an ELISA. Soluble VEGF, sFLT-1 and sKDR concentration levels were significantly higher in AML patients at diagnosis when compared to the levels in normal controls. sVEGF, sFlt1 and the sVEGF/sFlt1 ratio were significantly higher in non responders when compared to responders (P < 0.001 for all). However, there was no significant difference regarding sKDR levels (P > 0.05). sVEGF, the sVEGF/sFlt1 ratio but not sFlt1 and sKDR levels were significantly elevated in those who did not survive, when compared to survivors. sVEGF, sFlt1 levels were significantly correlated to WBC counts (R = 0.93, P = 0.000, R = 0.56, P = 0.000, respectively); bone marrow blast cell counts (R = 0.92, P = 0.000; R = 56, P = 0.000, respectively); peripheral blood blast cell counts (R = 0.91, P = 0.000; R = 0.52, P = 0.000, respectively); sKDR was only correlated to peripheral blood blast cell counts(R=0.37,P=0.014). Cox regression analysis results with sVEGF, sFlt1, sKDR, sVEGF/sFlt1 ratio suggest that the most important predictor for AML outcome is the sVEGF/sFlt1 ratio.In conclusion, sVEGF/sVEGF ratio is independent predictor of AML patient out come, and its significance should be assessed when considering antiangiogenic therapy.