Primary biliary cirrhosis is associated with oxidative stress and endothelial dysfunction but not increased cardiovascular risk

Aim: Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti‐oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk. Methods: Fifty‐one PBC patients and 34 control subjects were studied. Lipid soluble vitamins A, and E in addition to ascorbate and carotenoids were measured to assess anti‐oxidant status. C‐reactive protein, hydroperoxides and adhesion molecules sICAM‐l/sVCAM‐l were assessed as serological measures of endothelial function. Finally, measures of vascular compliance were assessed by applanation tonometer. Results: CRP, sICAM and sVCAM were all significantly higher in PBC patients (469.14 vs 207.13, P < 0.001; 768.12 vs 308.03,P < 0.001; 708.40 vs 461.31, P < 0.001) whilst anti‐oxidant vitamin levels were lower in PBC patients, with ascorbate, vitamin E and vitamin A all significantly lower in PBC patients (39.91 vs 72.68, P < 0.001; 2.63 vs 3.14, P = 0.02; 1.08 vs 1.81, P < 0.001). Despite these findings PBC patients have a lower pulse wave velocity than control subjects (8.22 m/s vs 8.78 m/s, P = 0.022). Conclusion: PBC patients appear to have reduced vascular risk as assessed by pulse wave velocity but concurrently have evidence of endothelial dysfunction, inflammation and anti‐oxidant deficiency.     

Coronary artery endothelial dysfunction associated with sleep apnea

There is little information about coronary artery endothelial dysfunction in patients with sleep apnea. We evaluated relation between severity of sleep apnea and coronary artery endothelial dysfunction. In all, 26 patients without significant coronary stenoses were enrolled. Endothelial function was estimated by measuring coronary vasoreactivity in response to acetylcholine infusion (10(-7) mol/L) into coronary arteries. Vasoconstriction rate was defined as ([lumen diameter after isosorbide dinitrate injection - lumen diameter after acetylcholine injection]/lumen diameter after isosorbide dinitrate injection × 100). Vasoconstriction rate was calculated at each major coronary artery and the highest value was used for that patient. Overnight sleep study was performed and the apnea-hypopnea index (AHI) was calculated as the mean number of apneas and hypopneas per hour of sleep. There was significant correlation between AHI and vasoconstriction rate (P = .04). There is significant correlation between severity of sleep apnea and endothelial function of coronary arteries.     

Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis.

AIMS: Coronary endothelial dysfunction (CED) precedes atherosclerosis and is associated with cardiovascular events. Both CED and erectile dysfunction (ED) are partly mediated by impairment in the nitric oxide pathway. ED is associated with established coronary atherosclerosis, but its relationship with early coronary atherosclerosis and CED is unknown. This study was designed to test the hypothesis that CED is associated with ED in men with early coronary atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous competitive inhibitor of nitric oxide synthase and has been shown to be an independent marker for cardiovascular disease. METHODS AND RESULTS: Fifty-six men without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing were studied. ADMA levels were determined and all men were asked to complete the International Index of Erectile Function-5 questionnaire to assess erectile function. Patients were divided according to the presence (n = 32) or absence (n = 24) of CED. Men with CED had significant impairment of erectile function (P = 0.008) and significantly higher ADMA levels (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal endothelial function. Erectile function positively correlated with coronary endothelial function. This correlation was independent of age, body mass index, high-density lipoprotein, C-reactive protein, homeostasis model assessment of insulin resistance index, and smoking status. CONCLUSION: CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.     

Abdominal obesity is associated with increased risk of acute coronary events in men.

AIMS: The purpose of the study was to investigate the associations of abdominal obesity and overall obesity with the risk of acute coronary events. METHODS AND RESULTS: Body mass index indicating overall obesity and waist-to-hip ratio and waist circumference indicating abdominal obesity were measured for 1346 Finnish men aged 42-60 years who had neither cardiovascular disease nor cancer at baseline. There were 123 acute coronary events during an average follow-up of 10.6 years. In Cox regression analyses adjusted for confounding factors, waist-to-hip ratio (P=0.009), waist circumference (P=0.010) and body mass index (P=0.013) as continuous variables were associated directly with the risk of coronary events. These associations were in part explained by blood pressure, diabetes, fasting serum insulin, serum lipids, plasma fibrinogen, and serum uric acid. Waist-to-hip ratio of > or =0.91 was associated with a nearly threefold risk of coronary events. Waist-to-hip ratio provided additional information beyond body mass index in predicting coronary heart disease, whereas body mass index did not add to the predictive value of waist-to-hip ratio. Abdominal obesity combined with smoking and poor cardiorespiratory fitness increased the risk of coronary events 5.5 and 5.1 times, respectively. CONCLUSIONS: Abdominal obesity is an independent risk factor for coronary heart disease in middle-aged men and even more important than overall obesity. Since the effect of abdominal obesity was strongest in smoking and unfit men, the strategy for lifestyle modification to prevent coronary heart disease should address these issues jointly.     

Hepatic steatosis is associated with an increased risk of carotid atherosclerosis

AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.     

Malnutrition is independently associated with an increased risk of major cardiovascular events in adult patients with congenital heart disease

Background and aimsMalnutrition is found frequently during chronic diseases, and its prevalence and relation to disease outcome in adult patients with congenital heart disease (CHD) remains unknown.Methods and resultsA cohort of 393 consecutive stable congenital heart disease (CHD) patients was followed up in a single dedicated clinical unit. Demographic, clinical and laboratory parameters, along with a nutritional risk index (NRI), were studied, as well as major acute cardiovascular events (MACE), defined as arterial thrombotic events, heart failure requiring hospitalization or cardiovascular and non-cardiovascular mortality. The median age of the patients was 23 years (17–35) and 225 (57%) were males. Median plasma albumin concentration was 4.5 (4.2–4.7) g/dL, the body mass index was 23 (21–27) kg/m², the NRI was 112 (106–118), and 33 (8%) patients showed malnutrition (NIR<100). A worse NYHA functional class (II and III), total cholesterol and serum glucose levels were significant risk factors associated with malnutrition (NRI<100) in CHD patients. During a median follow-up of 8 (5–10) years, 39 (10%) CHD patients suffered a MACE. Multivariable Cox regression analysis showed that older patients (years) [HR 1.06 (1.04–1.09), p < 0.001], CHD patients with great anatomical complexity [HR 4.24 (2.17–8.27), p < 0.001] and those with a lower NRI [HR 0.95 (0.93–0.98), p = 0.001] had a significant worse MACE-free survival, being the NRI a better predictor of MACE than albumin concentration.ConclusionsA low NRI is independently associated with a significant increased risk of MACE in CHD patients.     

Sarcopenia is associated with an increased risk of advanced colorectal neoplasia

Background/aims

Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear.

Methods

This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia.

Results

Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P < 0.001) than those without sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032–1.093; P < 0.001), male sex (odds ratio 1.749, 95% confidence interval 1.008–3.036; P = 0.047), and sarcopenia (odds ratio 2.347, 95% confidence interval 1.311–4.202; P = 0.004) were associated with an advanced colorectal neoplasia.

Conclusion

Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

     

Hypertension with primary aldosteronism is associated with increased carotid intima‐media thickness and endothelial dysfunction

Patients with primary aldosteronism induced hypertension are more likely to experience cardiovascular events compared to patients with essential hypertension. Primary aldosteronism may therefore have distinct adverse effects on cardiovascular structure and function, independent of hypertension. However, current data on such effects of primary aldosteronism are conflicting. The aim of the present study was to investigate the influence of primary aldosteronism on vascular structure and endothelial function, using intima‐media thickness as a vascular remodeling index and flow‐mediated dilation as a functional parameter. In total, 70 participants were recruited from patients with resistant hypertension. Twenty‐nine patients diagnosed with primary aldosteronism and 41 patients with essential hypertension were prospectively enrolled. Primary aldosteronism was due to aldosterone‐producing adenoma in 10 cases and due to idiopathic adrenal hyperplasia in 19 cases. All patients underwent ultrasound of the common carotid intima‐media thickness and flow‐mediated dilation of the brachial artery. Primary aldosteronism patients had significantly lower flow‐mediated dilation (3.3 [2.4‐7.4] % vs 14.7 [10.3‐19.9] %, P < 0.01) and significantly higher carotid intima‐media thickness (0.9 [0.7‐1.0] mm vs 0.8 [0.6‐0.9] mm, P = 0.02) compared to patients with essential hypertension. These differences remained significant after adjusting for age, sex, diabetes mellitus, 24‐hours systolic blood pressure, and smoking (P < 0.01). No differences in either outcome were observed between the adenoma and adrenal hyperplasia groups (both P > 0.05). Hypertensive patients with hyperaldosteronism appear to exhibit deteriorative effects on both vascular structure and function, independent of hypertension.     

Aortic valve sclerosis is associated with systemic endothelial dysfunction

OBJECTIVES: We sought to examine the association between aortic valve sclerosis (AVS) and systemic endothelial manifestations of the atherosclerotic process. BACKGROUND: Clinical and experimental studies suggest that AVS is a manifestation of the atherosclerotic process. Systemic endothelial dysfunction is an early sign of the atherosclerotic process and can be assessed by ultrasonography of the brachial artery. METHODS: A total of 102 in-hospital patients (76 men; mean age 63.5 +/- 9.7 years) referred to the stress echocardiography laboratory underwent: 1) transthoracic echocardiography, with specific assessment of AVS (thickened valve leaflets with a transaortic flow velocity <2.5 m/s); 2) stress echocardiography; 3) coronary angiography, with evaluation of the Duke score (from 0 [normal] to 100 [most severe disease]); and 4) an endothelial function study, with assessment of endothelium-dependent, post-ischemic, flow-mediated dilation (FMD). RESULTS: Aortic valve sclerosis was present in 35 patients (group I) and absent in 67 (group II). Groups I and II were similar in terms of the frequency of stress-induced wall motion abnormalities (35.3% vs. 19.4%, p = NS) and the angiographic Duke score (33.8 +/- 28.6 vs. 35.2 +/- 29.1, p = NS). Patients with AVS showed a markedly lower FMD than those without AVS (2.2 +/- 3.5% vs. 5.3 +/- 5.3%, p < 0.01). On multivariate analysis, only FMD was highly predictive of AVS, with an odds ratio of 1.18 for each percent decrease in FMD (95% confidence interval 1.05 to 1.32; p = 0.01). CONCLUSIONS: Aortic valve stenosis is associated with systemic endothelial dysfunction. This observation may provide a mechanistic insight into the emerging association between AVS and cardiovascular events.