Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy.

AIM: The study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor of adenoma after negative baseline colonoscopy. METHOD: A retrospective cohort study was conducted on 1522 health-check individuals who underwent two consecutive colonoscopies at Taipei Veterans General Hospital between 2003 and 2010. Those developing an adenoma after an initial negative baseline colonoscopy (adenoma group) were compared with those in whom the second colonoscopy was negative (nonadenoma group). Anthropometric measurements, biochemical tests and the presence of NAFLD were compared between the two groups. RESULTS: The adenoma group had a higher prevalence of NAFLD than the nonadenoma group (55.6% vs 38.8%; P < 0.05). On multivariate logistic regression analysis, NAFLD was an independent risk factor (OR = 1.45, 95% CI: 1.07-1.98) for adenoma formation after a negative baseline colonoscopy. The risk of colorectal adenoma increased when NAFLD patients had other morbidities including metabolic syndrome, hypertension or smoking (OR = 2.85, 4.03 and 4.17). CONCLUSION: NAFLD is an independent risk factor for colorectal adenoma formation after a negative baseline colonoscopy. The risk is higher in individuals with NAFLD and other comorbidities, such as hypertension, smoking or metabolic syndrome.

Herpes simplex virus infection and erectile dysfunction: a nationwide population-based study.

Both erectile dysfunction (ED) and herpes simplex virus (HSV) infections are related to cardiovascular events. However, the relationship between ED and HSV infections remains undetermined. The aim of our study was to investigate the possible influence of HSV infections on the development of ED using the Taiwan National Health Insurance database. We identified patients with HSV type 1 or type 2 infections from the 1 000 000 sampling cohort data set. Male patients of age 18 years or older who had been diagnosed as cases of HSV infection since January 1, 2001 were enroled. Patients with previous history of stroke, spinal cord injury or malignancy were excluded. A control group was selected, comprising male patients without HSV infection, stroke, spinal cord injury or malignancy. The age, time of enrolment and comorbidities were matched in the two groups. A total of 1 717 HSV subjects (mean age 43.29 ± 15.97 years) and 6 864 control subjects were enroled. During an average of 3.91 ± 1.93 years' follow-up, HSV-infected subjects experienced a higher incidence of ED than control subjects (1.7% vs. 0.7%, respectively). The log-rank test showed that patients with HSV infections had a significantly higher incidence of ED than those without HSV infections (p < 0.001). After Cox proportional hazard regression model analysis, HSV infections were independently associated with the increased risk of ED (hazard ratio, 2.90; 95% CI, 1.82-4.63, p < 0.001). In conclusion, HSV infections were associated with risk of ED in this cohort.

Cirrhotic patients at increased risk of peptic ulcer bleeding: a nationwide population-based cohort study.

BACKGROUND: Few large population-based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients. AIMS: To investigate if cirrhotic patients have higher risk of PUB than the general population and to identify possible risk factors of PUB in cirrhotic patients. METHODS: Using the National Health Insurance Research Database, a nationwide population-based dataset in Taiwan and matching age, gender, comorbidities and ulcerogenic medication by propensity score, 4013 cirrhotic patients, 8013 chronic hepatitis patients and 7793 normal controls were compared. The log-rank test was used to analyse differences in accumulated PUB-free survival rates between the groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB in all patients and identified risk factors of PUB in cirrhotic patients. RESULTS: During the 7-year follow-up, cirrhotic patients had significantly higher incidences of PUB than chronic hepatitis patients and controls, respectively (P < 0.001 by log-rank test). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of PUB (hazard ratio: 4.22; 95% CI 3.37-5.29, P < 0.001) after adjusting for age, gender, economic status, underlying comorbidities and ulcerogenic medication. Age, male, diabetes, chronic renal disease, history of gastro-oesophageal variceal bleeding and use of nonsteroidal anti-inflammatory drugs were risk factors for PUB in cirrhotic patients. CONCLUSION: Cirrhotic patients have a significantly higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like age, gender, economic status, underlying comorbidities and ulcerogenic medication.

Chronic obstructive pulmonary disease: an independent risk factor for peptic ulcer bleeding: a nationwide population-based study.

BACKGROUND: Peptic ulcer bleeding remains a major healthcare problem despite decreasing prevalence of peptic ulcer disease. The role of chronic obstructive pulmonary disease (COPD) in the risk of peptic ulcer bleeding has not yet been established. AIM: To determine if COPD patients have a higher risk of peptic ulcer bleeding than the general population and to identify the risk factors of peptic ulcer bleeding in COPD patients. METHODS: From Taiwan's National Health Insurance research database, 62,876 patients, including 32,682 COPD and 30,194 age-gender-matched non-COPD controls, were recruited. Cox proportional hazard regression was performed to evaluate independent risk factors for ulcer bleeding in all patients and to identify risk factors in COPD patients. RESULTS: During the 8-year follow-up, COPD patients had a significant higher rate of peptic ulcer bleeding than the control group (P < 0.001, by log-rank test). By Cox proportional hazard regression analysis, COPD [hazard ratio (HR) 1.93, 95% CI 1.73-2.17] was an independent risk factor after adjusting for age, gender, underlying comorbidities and ulcerogenic medication. Age > 65 years, male, comorbidities of hypertension, diabetes, heart failure, history of peptic ulcer disease, and chronic renal disease and use of nonsteroidal anti-inflammatory drugs were risk factors of ulcer bleeding in COPD patients. CONCLUSION: Patients with chronic obstructive pulmonary disease have a higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like underlying comorbidities and ulcerogenic medication.

Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.

BACKGROUND: Clopidogrel does not inhibit prostaglandin synthesis. As a result, clopidogrel's incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower than aspirin's. AIM: To compare the healing rate in aspirin-related dyspeptic ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI plus clopidogrel. METHODS: Patients with aspirin-related nonbleeding symptomatic ulcers were randomised to receive rabeprazole (20 mg/day) plus aspirin (100 mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The primary endpoint was the successful treatment of PUD as characterised by intention-to-treat at the end of therapy. RESULTS: Two hundred and eighteen patients (109 in the aspirin group and 109 in the clopidogrel group) were enrolled. There were no statistical demographic differences between the group that received aspirin and the group that received clopidogrel. The PUD treatment success rate was also statistically equal between the clopidogrel and aspirin groups (86.2% vs. 90.0%, P = 0.531). Neither group experienced ulcer-related bleeding. Multivariate logistic regression analysis showed that large ulcer size (>10 mm) (OR: 6.29, 95% CI: 2.58-15.37) and past history of PUD (OR: 3.69, 95% CI: 1.24-10.97) were important predictors of unsuccessful therapy for aspirin-related PUD. CONCLUSIONS: Rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel in treating aspirin-related symptomatic PUD. Large ulcer size (>10 mm) and past history of PUD are important predictors of unsuccessful therapy (NCT 01037491).

Ambulatory pulse pressure as a novel predictor for long-term prognosis in essential hypertensive patients.

The prognostic value of ambulatory blood pressure (BP) monitoring for long-term prognosis varies in recent studies. The study aimed to investigate the role of ambulatory BP parameters in mortality and cardiovascular (CV) events in hypertensive patients. A series of 412 participants (59.3 ± 4.0 years) who received ambulatory BP monitoring for their fluctuated BP, either untreated or treated since 1995, were enroled. The mortality and CV events were obtained by follow-up and linked to the National Death Registry in Taiwan. There were 233 untreated and 179 treated patients. The latter were older with more comorbidity when compared with the former. After follow-up for 8.5 ± 1.7 years, both ambulatory systolic BP and pulse pressure (PP) could predict all-cause mortality, non-CV mortality, CV disease and stroke after adjusting for baseline covariates. However, only ambulatory PP could predict CV mortality and coronary heart disease. Ambulatory PP is better than ambulatory systolic BP, particularly in prediction of all-cause mortality. There was no predictive value of office BP in any outcome. In conclusion, ambulatory PP is a good predictor for long-term outcomes in hypertensive patients. The parameters of ambulatory rather than office BP could be applied for risk stratification either before or under antihypertensive treatment.

A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor.

Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 x 10⁻²5), rs495828 (P=3.5 x 10⁻8) and rs8176746 (P=9.3 x 10⁻5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.

Clinical predictors of the response to short-term thiazide treatment in nondiabetic essential hypertensives.

Blood pressure (BP) response to diuretics is varied in hypertensive patients. This study aimed to identify the patients who may respond better or worse to thiazide diuretics. Nondiabetic patients with treated or untreated hypertension were evaluated if they did not take diuretics and their office systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg. Diet and life style modification were advised in addition to the concomitant medication, if there were, for 2 weeks. Additional hydrochlorothiazide 50 mg was given per day for another 2 weeks. Both office and 24-h ambulatory BP were checked. The changes of office SBP were used for the response to thiazide treatment. A total of 92 patients were enrolled. Compared with those in the quartile of worst response, patients in the quartile of best response were older with increased baseline SBP and pulse pressure (PP) and reduced heart rate. Reduced baseline awake, but not increased sleep DBP was associated with better response to thiazide. Besides, baseline age, SBP and PP were correlated to the response to thiazide treatment. Among these variables, increased baseline mean BP independently predicted the best and reduced SBP predicted the worst responders. Accordingly, patients with higher mean BP respond better to thiazide treatment no matter with or without concomitant medication. Patients with mainly diastolic hypertension with lower SBP responded poorly to thiazide treatment. The findings may help to individualized use of thiazide in nondiabetic hypertensives.

Direct effect of statins on homocysteine-induced endothelial adhesiveness: potential impact to human atherosclerosis.

BACKGROUND: Although homocysteine (HCY) is a risk factor for cardiovascular diseases, recent clinical trials failed to show the benefits by reducing plasma HCY. Alternative strategy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, might be feasible. This study investigated HCY-induced endothelial adhesiveness with mononuclear cells (MNCs) from patients with coronary artery disease (CAD). The direct endothelial protective effects of statins were also examined. MATERIALS AND METHODS: Circulating MNCs were isolated from 14 stable CAD patients and 7 age- and gender-matched healthy subjects. Superoxide production of MNCs was determined by Ultra-weak and luminol-enhanced chemiluminescence. Human aortic endothelial cells (HAECs) were used for endothelial adhesiveness to MNCs or U937 human monocytic cells. Endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were examined by Western blot. RESULTS: Superoxide production of MNCs and plasma HCY and high-sensitive CRP levels were significantly increased in CAD patients than in healthy subjects. Stimulation with HCY enhanced the endothelial adhesiveness to MNCs from CAD patients or to U937 cells in a dose-dependent manner, whereas it was obscure with MNCs from healthy subjects. HCY stimulated endothelial VCAM-1 but not ICAM-1 expression in a dose-dependent manner. Monoclonal antibodies to VCAM-1 attenuated HCY-induced endothelial adhesiveness. Simvastatin or pravastatin significantly reduced HCY-induced VCAM-1 expression and endothelial adhesiveness to MNCs from CAD patients. CONCLUSION: Circulating MNCs were activated in CAD patients, which was critical to HCY-induced endothelial adhesiveness. Statins could directly reduce HCY-induced endothelial-MNC adhesion via VCAM-1 inhibition, suggesting its potential implication in HCY-related atherosclerosis disease.

Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients.

BACKGROUND: Serum matrix metalloproteinase (MMP) levels have been related to clinical outcomes in patients with coronary artery disease. Though statin treatment might reduce serum MMPs the change of levels after statin withdrawal remains obscure. MATERIALS AND METHOD: Sixty-one consecutive hypercholesterolaemic patients whose lipid profiles had been well controlled by regular simvastatin (20 mg day(-1)) treatment for more than 6 months were enrolled. Statin was discontinued after their lipid profiles reached the treatment goal of the ATP-III guideline. The lipid profiles, serum MMP-2, MMP-3 and MMP-9, tissue inhibitor of MMP and highly sensitive C-reactive protein (hsCRP) levels were measured on the day of simvastatin withdrawal and 120 days later. A further 50 hyperlipidaemia patients who had never received statin treatment (positive control group) and 28 healthy patients with normal lipid profiles (negative control group) were also studied as control groups. RESULTS: While the lipid profiles had been normalized, the levels of serum inflammatory markers were still higher in hypercholesterolaemic patients than in the healthy subjects. Up to 120 days after statin withdrawal there was no coronary event, but the lipid profiles and serum hsCRP levels had significantly rebounded in study patients. However, serum MMP-2 and MMP-9 levels remained unchanged and the MMP-3 level was even further reduced after statin withdrawal (115.04 +/- 84.54 vs. 92.71 +/- 66.71 ng mL(-1), P = 0.022). Moreover, the amplitudes of variation (%) of each parameter including MMPs, TIMP, hsCRP and lipid profiles after statin withdrawal were inversely correlated to their respective baseline levels before withdrawal (r = -0.702 to -0.284; P < 0.005). CONCLUSIONS: The effects of short-term discontinuation of statin were different on serum hsCRP and MMPs levels in hypercholesterolaemic patients. While lipid profiles and serum hsCRP level had rebounded the serum MMPs levels were still unchanged, or even reduced, suggesting the prolonged effect of statin treatment, especially on serum MMP-3 level up to 120 days after simvastatin withdrawal. Further work is required to clarify the situation both in terms of these serum markers and clinical effects.

Comparison of endothelial vasodilator function, inflammatory markers, and N-terminal pro-brain natriuretic peptide in patients with or without chronotropic incompetence to exercise test.

OBJECTIVE: To investigate the role of endothelial function, inflammatory markers, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with impaired chronotropic response during exercise test. METHODS: 86 subjects were enrolled. Treadmill exercise test was conducted according to the modified Bruce protocols. Brachial ultrasound was used to measure endothelium dependent flow mediated vasodilatation (FMD). Chronotropic incompetence was defined as either failure to achieve 85% of the age predicted maximum heart rate or a low chronotropic index (< 0.8). RESULTS: Of the 86 patients, 20 (23%) exhibited chronotropic incompetence. The patients were divided into three groups according to chronotropic index: group 1, < 0.8 (n = 20); group 2, 0.8-1.0 (n = 26); and group 3, > 1.0 (n = 40). Patients with impaired chronotropic response had significantly lower FMD than those with higher chronotropic response (mean (SD) 2.8 (1.9)% v 5.0 (2.8)% v 5.3 (2.5)%, p = 0.002, for groups 1, 2, and 3, respectively). Serum concentrations of high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), and NT-proBNP were significantly higher in group 1 than in groups 2 and 3 (hsCRP: 19 (12) v 9 (6) v 9 (6) mg/l, p < 0.05; MCP-1: 140 (51) v 133 (60) v 108 (46) pg/ml, p = 0.046; NT-proBNP: 4760 (1980) v 3710 (850) v 3910 (1060) mg/l, p = 0.019, respectively). In addition, chronotropic index was significantly related to FMD (r = 0.380, p = 0.001) and inversely related to hsCRP (r = -0.267, p = 0.013). By multivariate analysis, impaired chronotropic response was significantly related to endothelial dysfunction (p = 0.012). CONCLUSION: Patients with impaired chronotropic response to graded exercise had endothelial dysfunction, enhanced systemic inflammation, and higher NT-proBNP concentrations. These findings may partly explain the mechanism of chronotropic incompetence as a predictor of cardiovascular risk and increased mortality.

Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery disease.

BACKGROUND: Recent evidence suggests the important role of matrix metalloproteinases (MMPs) in the progression of atherosclerosis and development of clinical events. We assessed the prognostic value of different plasma MMPs in patients with stable coronary artery disease (CAD). MATERIALS AND METHODS: A total of 165 consecutive nondiabetic patients with angiographically significant CAD (n = 150) or normal coronary angiograms despite exercise-induced myocardial ischemia (cardiac syndrome X, n = 15) and 17 normal subjects were evaluated. In each subject, plasma inflammatory markers including high sensitivity C-reactive protein (hsCRP) and MMP-2, 3 and 9 were measured. In CAD patients, major cardiovascular events including cardiac death, nonfatal myocardial infarction, unscheduled coronary revascularization and hospitalization as a result of unstable angina were prospectively followed up for more than 6 months. RESULTS: Plasma levels of MMPs were significantly higher in CAD patients than in those with cardiac syndrome X and in normal subjects (MMP-2: 914.76 +/- 13.20 vs. 830.79 +/- 31.95 vs. 783.08 +/- 28.40 ng mL(-1), P = 0.002; MMP-3: 129.59 +/- 4.21 vs. 116.86 +/- 8.09 vs. 91.71 +/- 9.55 ng mL(-1), P = 0.011; MMP-9: 31.42 +/- 2.84 vs. 11.40 +/- 5.49 vs. 6.71 +/- 2.89 ng mL(-1), P = 0.006). In CAD patients, there were 48 major cardiovascular events during a mean follow-up period of 17.74 +/- 0.85 months. The numbers of diseased vessels (HR = 2.19, 95% CI 1.20-1.02, P = 0.011), plasma hsCRP (HR = 2.21, 95% CI 1.18-4.11, P = 0.013) and MMP-3 level (HR = 2.46, 95% CI = 1.15-5.28, P = 0.021) were associated with the development of cardiovascular events. However, only the plasma MMP-3 level was an independent predictor of the adverse events in CAD patients (HR = 2.47, 95% CI 1.10-5.54, P = 0.028). CONCLUSIONS: Plasma MMP levels were increased in CAD patients. Plasma MMP-3 level, rather than hsCRP, was an independent prognostic marker for future cardiovascular events, suggesting its potential role in risk stratification and clinical management of stable CAD.