Ruey-Hsing Chou

Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction

Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction < 45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Plasma levels of FGF21 and N-terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP) were determined. All patients were followed up for 1 year, or till the occurrence of heart failure readmission or death. Totally 95 patients with diastolic dysfunction and 143 controls were enrolled. Circulating FGF21 level was correlated with echocardiographic parameters of diastolic function and LV end-diastolic pressure (LVEDP). In multivariate logistic analysis, FGF21 was significantly associated with diastolic dysfunction, either identified by echocardiographic criteria (odds ratio: 2.97, p = 0.012) or confirmed with LVEDP level (odds ratio: 3.73, p = 0.030). Both plasma FGF21 (log rank p < 0.0001) and NT-pro-BNP levels (log rank p = 0.0057) showed good predictive power to the 1-year adverse cardiac events. This finding suggested FGF21 could be involved in the pathophysiology of diastolic heart failure.

Antipsychotic treatment is associated with risk of atrial fibrillation: A nationwide nested case-control study.

BACKGROUND Antipsychotic agents are well known for their arrhythmigenic effect on ventricular arrhythmia. Though a few case reports observed the occurrence of atrial fibrillation (AF) after antipsychotic exposure, information about their implication in AF is limited. METHODS Based on the National Health Insurance Database in Taiwan, we conducted a nested case-control study to investigate the relationship between antipsychotics and AF. From 2001 to 2010, a total of 34,053 cases of AF and 34,919 matched controls were enrolled. Antipsychotic exposure was measured and binding affinity to neurotransmitter receptors was calculated. Both medical and psychiatric comorbidities were identified and adjusted in multivariate logistic regression analysis. RESULTS Current antipsychotic use was associated with a 17% increased risk of AF relative to nonusers (adjusted OR: 1.17, 95% CI: 1.10-1.26). A dose-dependent relationship of antipsychotic exposure and AF risk was observed (P for trend <0.001). Antipsychotics with higher binding affinity to muscarinic M2 receptors were associated with a higher incidence of AF. In subgroup analysis, subjects with preexisting hypertension, diabetes, or coronary artery diseases were at greater risk of developing AF following antipsychotic exposure. CONCLUSION Antipsychotic exposure was associated with increased risk of AF, especially for agents with higher cardiac muscarinic receptor binding affinity. Physicians should monitor the occurrence of new-onset AF, and strictly control underlying medical risk factors while prescribing antipsychotic agents to high-risk populations.

Association between serum uric acid and cardiovascular risk in nonhypertensive and nondiabetic individuals: The Taiwan I-Lan Longitudinal Aging Study

Serum uric acid level is a risk factor for cardiovascular disease (CVD). However, whether it is an independent risk factor or not remains controversial. We analyzed the association between serum uric acid level and cardiovascular risk. In total, 973 nonhypertensive and nondiabetic participants in the I-Lan Longitudinal Aging Study were eligible for this study. Subjects were divided into tertiles according to uric acid levels. The 10-year cardiovascular risk was calculated using Framingham risk score (FRS). Study subjects in the highest tertile of serum uric acid level were older, more likely to be male, and had higher systolic blood pressure, body mass index, carotid artery intima–media thickness and serum triglyceride, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol levels and lower serum high-density lipoprotein cholesterol levels (all p < 0.05). Subjects in the highest tertile had significantly higher FRS (p < 0.001). After adjusting for other risk factors, serum uric acid level remained associated significantly with the FRS (p < 0.05). In binary logistic regression analysis, the serum uric acid level was an independent predictive factor for high (≥20%) FRS (odds ratio 1.33, 95% confidence interval 1.10–1.68). These findings warrant attention to this cardiovascular risk factor in apparently healthy adults.

High health literacy is associated with less obesity and lower Framingham risk score: Sub-study of the VGH-HEALTHCARE trial

Backgrounds Lower health literacy (HL) is associated with several cardiovascular disease (CVD) risk factors such as diabetes, hypertension, and metabolic syndrome (MS). The aim of our study was to investigate the association between HL and the Framingham 10-year risk score of CVD. Methods From 2015–2016, 1010 subjects aged 23 to 88 years receiving health check-up in Taipei Veterans General Hospital had complete clinical evaluations and laboratory examinations. Fatty liver was diagnosed by ultrasonography. The short form questionnaire adapted from the Mandarin Health Literacy Scale was used to assess HL. The Framingham risk score was calculated by patient characteristics. Results Subjects with higher BMIs were associated with lower HL scores. The proportion of subjects with MS was higher in the lower health literacy score group (≤ 9) at 28.8%; further analysis found that lower HL was significantly associated with MS in women but not in men. The Spearman’s rho demonstrated that the HL score was significantly associated with the BMI-based (rho = -0.11; P < 0.001) or lipid-based (rho = -0.09; P < 0.004) Framingham risk score. Conclusions Higher HL scores were associated with less CVD risk such as lower BMIs, less MS in women, and less fatty liver disease. Furthermore, HL had an inverse association with the Framingham risk score as expected. Therefore, HL in patients with CVD risk should be improved and considered as an important issue in terms of CVD reduction.

Chronic hyperuricemia impairs blood flow recovery in the ischemic hindlimb through suppression of endothelial progenitor cells

Objective Chronic hyperuricemia is associated with cardiovascular disease, but its impact on endothelial progenitor cells (EPC) and ischemia-induced neovascularization remains unclear. Herein we investigated whether chronic hyperuricemia could impede blood flow recovery in response to tissue ischemia by suppression of EPC. Methods Human EPC were isolated and cultured in a high-level uric acid medium for functional testing. Cell proliferation, nitric oxide (NO) production and apoptosis assay were examined. A chronic hyperuricemia mouse model was established by potassium oxonate treatment and/or a high-level uric acid diet to evaluate the actions of chronic hyperuricemia on ischemia-induced blood flow recovery. After 4 weeks of drug treatment, hindlimb ischemia surgery was performed in the control and hyperuricemia mice. Blood flow recovery was followed up every week before and after ischemic surgery using a laser Doppler Perfusion Imager System. The circulating EPC number in the peripheral blood was determined by flow cytometry (Sca-1+/Flk-1+). Results Incubation with a high-level uric acid medium (10 mg/dL) significantly suppressed EPC proliferation, reduced NO production, and lessened phosphorylation of Akt and eNOS. Moreover, EPC treated with high-level uric acid increased reactive oxygen species production, promoted cellular apoptosis and senescence, and also inhibited EPC tube formation. Four weeks after hindlimb ischemia surgery, the chronic hyperuricemia mice had significantly reduced tissue reperfusion, EPC mobilization, and impaired neovascularization in the ischemic hindlimbs compared with the control mice. Conclusions Chronic hyperuricemia impaired blood flow recovery and EPC mobilization in response to tissue ischemia, and these effects could have occurred through suppression of EPC.

The impact of chronic hepatitis B infection on major adverse cardiovascular events and all-cause mortality in patients with diabetes: a nationwide population-based study from Taiwan

Objectives The association between hepatitis B virus (HBV) infection and cardiovascular disease remains uncertain. This study explored long-term hard endpoints (ie, myocardial infarction and ischaemic stroke) and all-cause mortality in diabetic patients with chronic HBV infection in Taiwan from 2000 to 2013. Design This study was retrospective, longitudinal and propensity score-matched. Setting Nationwide claims data for the period 2000–2013 were retrieved from Taiwan’s National Health Insurance Research Database. Participants The study included 40 162 diabetic patients with chronic HBV infection (HBV cohort) and 40 162 propensity score-matched diabetic patients without HBV infection (control cohort). Chronic HBV infection was identified based on three or more outpatient clinic visits or one hospital admission with a diagnosis of HBV infection. Main outcome measures Primary outcomes were major adverse cardiovascular events (MACE, including myocardial infarction and ischaemic stroke), heart failure and all-cause mortality. Results During the median follow-up period of 5.3±3.4 years, the HBV cohort had significantly lower risks of myocardial infarction (adjusted HR (aHR)=0.49; 95% CI 0.42 to 0.56), ischaemic stroke (aHR=0.61; 95% CI 0.56 to 0.67), heart failure (aHR=0.50; 95% CI 0.43 to 0.59) and all-cause mortality (aHR=0.72; 95% CI 0.70 to 0.75) compared with the control cohort. The impact of HBV infection on the sequential risk of MACE was greater in patients with fewer diabetic complications. Conclusions Chronic HBV infection was associated with decreased risk of MACE, heart failure and all-cause mortality in patients with diabetes. Further research is needed to investigate the mechanism underlying these findings.

Metabolic Surgery Ameliorates Cardiovascular Risk in Obese Diabetic Patients: Influence of Different Surgical Procedures

BACKGROUND In recent years, bariatric surgery was found to have therapeutic potential for the treatment of type 2 diabetes (T2D) in severely obese patients (body mass index [BMI] ≥35 kg/m2) and to reduce cardiovascular disease (CVD) risk and mortality. However, the benefit of CVD risk reduction after metabolic surgery in nonseverely obese T2D patients (BMI <35 kg/m2) remained to be proven. OBJECTIVE To evaluate the CVD risk after metabolic surgery in T2D patients using The UK Prospective Diabetes Study score. SETTING Tertiary referral general hospital, Taiwan, Republic of China. METHODS Outcomes of 392 patients (235 women and 147 men) who had undergone sleeve gastrectomy (87) or gastric bypass (305) for treatment of T2D with 1-year follow-up were assessed. Data were prospectively collected for study, and cerebral and coronary heart disease risk was calculated by using The UK Prospective Diabetes Study risk engine. Outcomes of patients who had undergone different surgical procedures were assessed. RESULTS One year after surgery, weight and glycemic control with complete and partial remission of T2D were significant in most of the patients. The 10-year coronary heart disease risk and fatal coronary heart disease risk were also reduced from 8.8% to 4.6% and from 4.6% to 2.1%, respectively (both P < .001). Similar CVD risk reduction was seen in both patients with BMI ≥35 and BMI <35. Multivariable analysis confirmed that surgical procedure of sleeve gastrectomy was a negative independent predictor of CVD risk reduction after metabolic surgery. CONCLUSION The present study confirms the efficacy of metabolic surgery for the T2D treatment and reduction of CVD risk up to 50% 1 year after surgery. Gastric bypass surgery has more power on CVD risk reduction than sleeve gastrectomy.

Circulating Fibroblast Growth Factor 21 is Associated with Subsequent Renal Injury Events in Patients Undergoing Coronary Angiography

Fibroblast growth factor 21 (FGF21) is a regulator of glucose homeostasis, and is suggested to have protective effect on diabetic nephropathy. Its impact on non-diabetic kidney disease is unclear. To investigate the impact of FGF21 on contrast-induced nephropathy (CIN), 531 subjects underwent elective coronary angiography (CAG) were enrolled. Baseline creatinine and FGF21 were obtained before CAG. Patients were grouped into tertiles according to their FGF21 concentration. Creatinine was obtained 48 hours after CAG, and every 6 months in the follow-up period. Renal function decline was defined as >30% reduction of eGFR from baseline. All subjects were followed up till December 2016, or till the occurrence of major adverse cardiovascular events (MACE). Patients with higher FGF21 concentration were older, had higher incidence of hypertension, diabetes, chronic kidney disease, and heart failure. Thirty-four cases of CIN and 111 cases of renal function decline were identified during mean follow-up of 2.3 ± 1.3 years. Circulating FGF21 level was independently associated with CIN (aOR: 4.66, 95% CI: 1.29–16.86, p = 0.019) and renal function decline (aHR: 7.98, 95% CI: 4.07–15.66, p < 0.001) whether diabetes was present or not. In conclusion, circulating FGF21 level is independently associated with the incidence of CIN and subsequent kidney injury in patients undergoing CAG.

Increased activin A levels in prediabetes and association with carotid intima-media thickness: a cross-sectional analysis from I-Lan Longitudinal Aging Study

Activin A and its binding protein follistatin may be crucial in glucose homeostasis, as multifunctional proteins mediating inflammatory and anti-inflammatory effects. However, clinical data on the activin A level in prediabetes, and the association between the circulating activin A level and carotid intima-media thickness (cIMT), are lacking. We aimed to investigate activin A and follistatin levels and their associations with cIMT. In total, 470 inhabitants of I-Lan county (235 men; mean age 69 ± 9 years) with measurements of serum activin A and follistatin levels were included. Patients with prediabetes and diabetes had significantly increased activin A concentrations compared with those in the normal glycemic group (both p < 0.001). A multivariable logistic regression model demonstrated that the circulating activin A level was associated with prediabetes and diabetes independently of other risk factors. Moreover, the circulating activin A levels were associated positively with cIMT in prediabetes (rs = 0.264, p = 0.001). In conclusion, activin A level, but not follistatin, was elevated independent of demographic variables with borderline significance and was correlated positively with cIMT in prediabetes. Activin A and follistatin levels were elevated in diabetes. In addition, elevated activin A was an independent risk factor for prediabetes and diabetes.

Serum Corin Level Is Associated With Subsequent Decline in Renal Function in Patients With Suspected Coronary Artery Disease

Background Higher circulatory corin in patients with cardiac diseases is associated with improved cardiovascular outcomes, and chronic cardiac dysfunction is a well‐known cause of progressive renal dysfunction. This study aimed to determine the role of serum corin in predicting short‐term and long‐term renal outcomes after contrast exposure in patients with suspected coronary artery disease. Methods and Results Four hundred one patients who had received coronary angiography were enrolled. Serum corin levels were determined before administration of contrast media. Contrast‐induced nephropathy was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from baseline within 48 hours after the procedure. Progressive renal dysfunction was defined as >50% decrease in estimated glomerular filtration rate after discharge. All patients were followed up for at least 1 year or until the occurrence of death after coronary angiography. Overall, contrast‐induced nephropathy occurred in 23 (5.7%) patients. During a median follow‐up of 529 days, 44 (11.0%) cases had subsequent decline in renal function. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, lower corin level was found to be independently associated with higher risk for progressive renal dysfunction (hazard ratio, 0.23; 95% confidence interval, 0.12–0.44) but not for contrast‐induced nephropathy. This inverse correlation remained evident in patients with underlying chronic kidney disease, coronary artery disease, or heart failure. Conclusions Lower baseline serum corin was associated with higher risk of renal function decline in patients undergoing coronary angiography. Further studies are needed to verify these results.