Chun-Chin Chang

Risk of New-Onset Diabetes Mellitus Versus Reduction in Cardiovascular Events With Statin Therapy

The Food and Drug Administration recently updated the safety warning concerning the association between statin therapy and new-onset diabetes mellitus (NODM). For prediabetes, little information is available for statins on cardiovascular outcome reduction and diabetogenic consequences. This study aimed to examine the risk of NODM and the reduction of cardiovascular events and death (MACE) after statin therapy in the prediabetic subjects. The medical and pharmacy claims of the prediabetic beneficiaries were retrieved from Taiwan National Health Insurance research database. The occurrence of NODM, MACE, and morbidity indexed by hospitalizations and emergency visits was ascertained by ambulatory and inpatient database. A propensity score-matched model was constructed for statin users and nonusers. During follow-up (4.1 ± 2.5 years), NODM and MACE occurred in 23.5% and 16.7%, respectively, of nonusers and 28.5% and 12.0%, respectively, of users. Statin therapy was associated with a greater risk of NODM (hazard ratio 1.20, 95% confidence interval 1.08 to 1.32) and less risk of MACE (hazard ratio 0.70, 95% confidence interval 0.61 to 0.80), both in dose-dependent fashions. The earlier and more persistent use correlated with the greater increase in risk of NODM offset by the proportionally larger reduction in MACE. Furthermore, the early persistent users had the lowest rate of hospitalizations and emergency visits. In conclusion, our findings suggested that the relation between NODM and therapeutic advantages of statins was parallel in the prediabetic population. Treatment benefits outweighed diabetic consequences in subjects receiving the earlier and more persistent treatment.

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.

Determinants of low-density lipoprotein cholesterol goal attainment: Insights from the CEPHEUS Pan-Asian Survey

Background: Previous studies have reported that the attainment of goals for low‐density lipoprotein cholesterol (LDL‐C) are globally suboptimal, but contemporary data are scarce. The CEntralized Pan‐Asian survey on tHE Under‐treatment of hypercholeSterolemia (CEPHEUS‐PA) is the largest evaluation of pharmacological treatment for hypercholesterolemia in Asia. The study reported here analyzed the Taiwan cohort in CEPHEUS‐PA to identify the determinants of successful treatment. Methods: The patients eligible for this study were adults (≥18 years old) with hypercholesterolemia and with at least two coronary heart disease (CHD) risk factors who had been receiving lipid‐lowering drugs for at least 3 months before enrollment, without adjustment for at least 6 weeks before enrollment. Demographic and clinical information and lipid concentrations were recorded. Cardiovascular risk levels and LDL‐C targets were determined using the updated Adult Treatment Panel III. Results: In this group of 999 Taiwanese patients, 50%, 25%, and 24% had LDL‐C goals set at <70 mg/dL, <100 mg/dL, and <130 mg/dL, respectively. The overall attainment rate was 50%, with the lowest rate in patients set at the most stringent target (22%), followed by those whose therapeutic goals were <100 mg/dL (69%) and <130 mg/dL (87%). The success of LDL‐C control was lower in patients with multiple risk factors other than CHD or its equivalents than in those without these multiple risk factors (37% vs. 53%, p < 0.001), and lower in patients with metabolic syndrome than in those without (43% vs. 66%, p < 0.001). Baseline LDL‐C and cardiovascular risk were inversely associated with goal attainment, whereas treatment with statins was directly associated with the achievement of LDL‐C goals. Patients with diabetes (odds ratio 0.49, 95% confidence interval 0.29–0.84, p = 0.010) and with metabolic syndrome (odds ratio 0.15, 95% confidence interval 0.05–0.40, p < 0.001) were less likely to be treated with statins. Conclusion: This study showed that there is a discrepancy between the updated Adult Treatment Panel III recommendations for LDL‐C control and the control attained by this group of Taiwanese patients. In particular, treatment with statins was largely underused in patients with diabetes and in those with metabolic syndrome. These findings highlight the need for more intensive treatment in high‐risk patients and those with multiple risk factors, particularly patients with metabolic syndrome.

Association between low-grade albuminuria and frailty among community-dwelling middle-aged and older people: a cross-sectional analysis from I-Lan Longitudinal Aging Study

Frailty is characterized by decreased physiological reserve and increased vulnerability to atherosclerosis and subsequent mortality. Recently, low-grade albuminuria has been proposed as an atherosclerotic risk factor. We aimed to investigate the relationship between low-grade albuminuria and frailty by using cross-sectional data among community-dwelling middle-aged and older people. Totally, 1,441 inhabitants of I-Lan County with normal urinary albumin excretion (urine albumin to urine creatinine ratio [UACR] <30 mg/g) were enrolled (677 men; mean age 63 ± 9 years, range from 50 to 91 years old). Assessment of frailty was based on the ‘Fried frailty phenotype’ criteria, including weight loss, grip strength, exhaustion, slowness and low physical activity. The study population was stratified into quartiles according to UACR levels. Age, body mass index, hypertension, diabetes, systolic blood pressure, insulin resistance, fasting glucose and high-sensitivity C-reactive protein levels were increased with the increment of UACR (P for trend <0.05). The prevalence of prefrailty/frailty and its components increased across the UACR quartiles. A multivariate stepwise logistic regression analysis revealed that UACR was independently associated with the likelihood of prefrailty/frailty (odds ratio 1.13, 95% CI 1.01–1.27). In conclusion, low-grade albuminuria is associated with the increased prevalence of prefrailty/frailty.

Obstructive sleep apnea and the risk of ischemic stroke in patients with atrial fibrillation

a Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan b Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Family Medicine Taipei Veterans General Hospital, Taipei Veterans General Hospital, Taipei, Taiwan e Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan f Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan g Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan h Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan i Department of Medical Informatics, University of Heidelberg, Heidelberg, Germany j Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC

Statin Therapy Reduces Future Risk of Lower-Limb Amputation in Patients With Diabetes and Peripheral Artery Disease

Context Although there is evidence to support the beneficial effects of statins on major cardiovascular events, few studies address the protective effect of statins on limb outcome. Objective To investigate whether the use of statin is associated with a risk reduction in lower-extremity amputation in type 2 diabetes mellitus (DM) patients with peripheral arterial disease (PAD). Design Observational cohort study. Setting A nationwide DM database in Taiwan from 2000 to 2011. Patients A total of 69,332 patients aged ≥20 years with DM and PAD were identified. Intervention Patients were divided into three groups: 11,409 patients were statin users, 4430 patients used nonstatin lipid-lowering agents, and 53,493 patients were nonusers. Main Outcome Measures The primary outcome was lower-extremity amputation. Secondary outcomes were in-hospital cardiovascular death and all-cause mortality. Results Compared with nonusers, statin users were associated with lower risks of lower-extremity amputation [adjusted hazard ration (aHR), 0.75; 95% confidence interval (CI), 0.62 to 0.90], in-hospital cardiovascular death (aHR, 0.78; 95% CI, 0.69 to 0.87), and all-cause mortality (aHR, 0.73; 95% CI, 0.69 to 0.77). In the propensity score matching analysis, the effect of statin on the risk of lower-extremity amputation was consistent. Only statin users were associated with the risk reduction of lower-extremities amputation (HR, 0.77; 95% CI, 0.61 to 0.97) and cardiovascular death (HR, 0.78; 95% CI, 0.68 to 0.89) when taking competing risk of death into consideration. Conclusions Compared with statin nonusers who were never treated with lipid-lowering drugs, this study found that statin users had a lower risk of lower-extremity amputation and cardiovascular death in patients with DM and PAD.

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.

The Association Between Serum Activin A Levels and Hypertension in the Elderly: A Cross-Sectional Analysis From I-Lan Longitudinal Aging Study

BACKGROUND Hypertension is an important risk factor for cardiovascular disease. Activin A, a member of the transforming growth factor-β cytokine family, has been shown to regulate blood pressure through the renin-angiotensin system. However, the relationship between activin A and blood pressure remains uncertain. The objective of this study was to determine whether serum activin A levels are associated with blood pressure. METHOD A total of 470 participants of I-Lan longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional analyses were performed, including comparisons of demographic characteristics, hypertensive status, and activin A levels. RESULTS Among the study participants (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were normotensive. Hypertensive patients had significantly higher serum activin A levels than normotensives (normotensive vs. hypertensive: 507 ± 169 vs. 554 ± 176 pg/ml, mean ± SD, P < 0.001). All subjects were divided into 3 tertiles on the basis of serum activin A levels. Increasing tertiles of activin A were associated with higher systolic blood pressure (SBP), diastolic blood pressure and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential confounding factors, serum activin A concentration was still significantly associated with SBP (P = 0.02) and PP (P = 0.03). CONCLUSIONS Serum activin A level was associated with SBP and PP. Further studies are required to assess their causal relationship and the clinical relevance.

Association between frailty and carotid intima media thickness and inflammatory marker in an elderly population

Frailty is a highly prevalent geriatric syndrome, characterized by increased vulnerability to subsequent morbidity and mortality. The association between frailty and preclinical atherosclerosis remains uncertain. The aim of the present study was to clarify the relationship between frailty, preclinical atherosclerosis and inflammatory markers in older adults.

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.