Shao-Yuan Chuang

Serum uric acid level as an independent risk factor for all‐cause, cardiovascular, and ischemic stroke mortality: A chinese cohort study

OBJECTIVEnThe association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality.nnnMETHODSnA prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels.nnnRESULTSnA total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively.nnnCONCLUSIONnHyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.

Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes: A nationwide population-based study

OBJECTIVE Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown. RESEARCH DESIGN AND METHODS The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization. RESULTS There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]). CONCLUSIONS Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.

Brachial-ankle vs carotid-femoral pulse wave velocity as a determinant of cardiovascular structure and function.

Carotid-femoral pulse wave velocity (cf-PWV) is a validated marker of arterial stiffening over the central arteries. Brachial-ankle pulse wave velocity (ba-PWV) integrates the mechanical properties from both the central and peripheral arteries and may be more representative than cf-PWV as arterial load for left ventricle (LV). We compared ba-PWV with cf-PWV for the association of cardiovascular structure and function in 320 subjects with various degrees of abnormality in cardiac structure and function. ba-PWV (by oscillometric technique) and cf-PWV (by tonometric technique) were measured simultaneously, and were highly correlated (r=0.79, P<0.001). Both ba-PWV and cf-PWV were significantly correlated with LV mass, but the correlation was better with ba-PWV (r=0.29 vs r=0.22, P=0.0219). While ba-PWV and cf-PWV were similarly significantly correlated with LV end-systolic elastance and mitral E/A ratio, ba-PWV had better correlation with isovolumic relaxation constant (r=0.34 vs r=0.27, P=0.0202) than cf-PWV. In addition, the correlation was also significantly stronger with ba-PWV than with cf-PWV for other indices of arterial stiffness, including carotid incremental modulus (r=0.59 vs 0.50, P=0.0013), effective arterial elastance (r=0.41 vs r=0.33, P=0.0081) and carotid augmentation index (r=0.38 vs r=0.32, P=0.0368). In conclusion, ba-PWV correlates better with LV mass and diastolic function and other indices of arterial function than cf-PWV, probably because ba-PWV encompasses a greater territory of arterial tree than cf-PWV.

Is Ischemic Stroke Risk Related to Folate Status or Other Nutrients Correlated With Folate Intake

Background and Purpose— Folate status was inversely associated with plasma homocysteine concentration, a potential risk factor of cardiovascular disease. However, it is uncertain whether folate is causally associated with risk of ischemic stroke (IS). We aimed to examine the association between IS incidence and folate intake, biochemical folate status, and folate associated nutrients. Methods— Information on baseline characteristics and food frequency questionnaire was collected in 1990 to 1993 and included for analyses data from 1772 adults over 40 years, who were free of stroke and cancer at baseline from the CardioVascular Disease risk FACtor Two-township Study. Multivariate Cox proportional hazard model was used to relate baseline nutrient status with IS event. Results— Over an average of 10.6 years of follow-up, 132 incident IS events were documented. Low folate intake (1st and 2nd quartiles) was significantly and independently associated with increased IS risk (HR=1.61; 95% CI: 1.04 to 2.48 and HR=1.82; 95% CI: 1.20 to 2.76) compared with those in the 3rd and 4th quartile combined, whereas no association was observed for plasma folate concentration. On the other hand, several nutrients correlated with dietary folate: vitamin B2, potassium, iron, vitamin A of plant origin, calcium were also associated with IS risk in an inverse linear manner with HR ranging from 1.5 to 1.9 for the first quartile. Conclusions— The protective association of dietary folate on IS risk may be in part through that of other correlated nutrients or other dietary components.

Derivation and Validation of Diagnostic Thresholds for Central Blood Pressure Measurements Based on Long-Term Cardiovascular Risks

OBJECTIVESnThis study sought to derive and validate outcome-driven thresholds of central blood pressure (CBP) for diagnosing hypertension.nnnBACKGROUNDnCurrent guidelines for managing patients with hypertension mainly rely on blood pressure (BP) measured at brachial arteries (cuff BP). However, BP measured at the central aorta (central BP [CBP]) may be a better prognostic factor for predicting future cardiovascular events than cuff BP.nnnMETHODSnIn a derivation cohort (1,272 individuals and a median follow-up of 15 years), we determined diagnostic thresholds for CBP by using current guideline-endorsed cutoffs for cuff BP with a bootstrapping (resampling by drawing randomly with replacement) and an approximation method. To evaluate the discriminatory power in predicting cardiovascular outcomes, the derived thresholds were tested in a validation cohort (2,501 individuals with median follow-up of 10 years).nnnRESULTSnThe 2 analyses yielded similar diagnostic thresholds for CBP. After rounding, systolic/diastolic threshold was 110/80 mm Hg for optimal BP and 130/90 mm Hg for hypertension. Compared with optimal BP, the risk of cardiovascular mortality increased significantly in subjects with hypertension (hazard ratio: 3.08, 95% confidence interval: 1.05 to 9.05). Of the multivariate Cox proportional hazards model, incorporation of a dichotomous variable by defining hypertension as CBP ≥ 130/90 mm Hg was associated with the largest contribution to the predictive power.nnnCONCLUSIONSnCBP of 130/90 mm Hg was determined to be the cutoff limit for normality and was characterized by a greater discriminatory power for long-term events in our validation cohort. This report represents an important step toward the application of the CBP concept in clinical practice.

Obesity pandemic, correlated factors and guidelines to define, screen and manage obesity in Taiwan.

The prevalence of obesity and associated chronic diseases has increased rapidly in Taiwan. Data from three consecutive Nutrition and Health surveys in Taiwan show that obesity prevalence has tripled for elementary school boys and doubled for girls since 1993–1996. About one‐third of boys (15.5% and 14.7% for overweight and obesity, respectively) and one‐quarter of girls were either overweight (14.4%) or obese (9.1%) in 2001–2002. For adults, obesity prevalence rates defined by body mass index ≥27u2003kgu2003m−2 increased from 10.5% in men and 13.2% in women in the 1993–1996 survey, to around 17% in 2005. Prevalence of overweight was around 20% in 1993–1996 for both men or women, and increased to 30% in 2005 for men. No change was found in women. The underprivileged regions usually had higher prevalence of obesity and associated diseases. Scientific bases for Taiwan obesity definition are set out together with the screening and management plans. High‐calorie intake was associated with obesity in young children (grades 1–2), but not in older children and adults. Physical inactivity and sedentary lifestyle‐related variables were associated with obesity in men and older boys. In addition, good dietary quality was associated with a lower risk of obesity independent of energy intake in elderly Taiwanese. More research is needed to find effective determinants and public health measures for obesity, and concerted efforts are required to combat this rising health problem.

Gender-specific risk factors for incident gout: a prospective cohort study

Previous reports suggested that gout incidence increased with serum uric acid (sUA) level. In addition to sUA, we aimed to examine the gender-specific risk factors for incident gout. A prospective study was conducted using data of the MJ Health Screening Center and outcome database from Taiwan’s National Health Insurance. Cox proportional hazard model was used for risk analysis of incident gout. During a mean follow-up of 7.31xa0years for 132,556 individuals aged ≥18xa0years, 1,606 subjects (1,341 men and 265 women) with clinical gout were defined. Hyperuricemia (sUA ≥7.7xa0mg/dL for men or ≥6.6xa0mg/dL for women) was the most important risk factor for gout development with a respective hazard ratio of 9.65 (95% confidence level, 8.53–10.9) for men and 9.28 (7.00–12.3) for women. The age-standardized sUA–gout relationship demonstrated a differential impact of sUA level on gout incidence between men and women. Metabolic comorbidities of hypertension, obesity, and hyperlipidemia were significantly associated with gout with respective HR of 1.32 (1.17–1.48), 1.30 (1.15–1.47), and 1.12 (0.99–1.26) for men and 1.34 (1.02–1.77), 2.15 (1.67–2.76), and 1.70 (1.32–2.19) for women. However, the relationship between diabetes and incident gout was not as prominent. The sex difference of sUA–gout relationship and the association between metabolic comorbidities and incident gout were demonstrated. Generalizability of these findings to other ethnic population needs further investigation.

White Coat Hypertension Is More Risky Than Prehypertension Important Role of Arterial Wave Reflections

Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r 2=0.451; partial r 2/model r 2=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09–7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.nn# Novelty and Significance {#article-title-40}Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r 2=0.451; partial r 2/model r 2=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09–7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.

Fibrinogen Independently Predicts the Development of Ischemic Stroke in a Taiwanese Population CVDFACTS Study

BACKGROUND AND PURPOSEnOf few prospective studies that have focused on the relationship between fibrinogen and ischemic stroke (IS) in Asian populations, the findings were inconsistent with those conducted in Western countries. Therefore, we aimed to investigate the temporal relationship between fibrinogen levels (plus several related parameters) and IS in a community-based study in Taiwan.nnnMETHODSnBaseline data from 3281 adults (>or=20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental IS status derived from insurance claims and death certificate records. Hazard ratios and 95% CIs of clotting factors (fibrinogen, factor VII, factor VIII, and antithrombin-III) for IS events were estimated using Cox proportional hazard models.nnnRESULTSnWith 10.4 years (average) follow-up, 128 persons developed IS (3.75 per 1000 person-years). As expected, elevated blood pressure and diabetes were independent predictors of IS events. A dose-response relationship was found in univariate analysis between IS risk and tertiles of fibrinogen (hazard ratio, 3.73; 2.19 to 1.00), factor VII (hazard ratio, 1.86; 1.35 to 1.00), and factor VIII (2.97; 1.70 to 1.00), respectively, but not for antithrombin-III. After adjusting for confounding and known risk factors, fibrinogen independently predicted IS events. A 72% increase (hazard ratio, 1.72; 1.02 to 2.90) in IS risk was observed for individuals with fibrinogen >or=8.79 mumol/L compared with those <7.03 micromol/L.nnnCONCLUSIONSnIn addition to hypertension and diabetes, fibrinogen independently predicted future IS risk. We suggest that fibrinogen may be considered in the risk assessment model for IS in the Taiwanese population.

Hyperuricemia and increased risk of ischemic heart disease in a large Chinese cohort

AIMSnThere is an ongoing discussion on whether serum uric acid (SUA) predicts ischemic heart disease (IHD) independently of other metabolic factors, which, if confirmed, would signify a role for uric acid in the pathogenesis of cardiovascular disease. We investigated whether such a relation exists for ethnic Chinese with low CVD risk.nnnMETHODS AND RESULTSnEnrolled, between 1994 and 1996, were 128,569 adults ≥ 20 years from four MJ Health Check-up Clinics in Taiwan. Excluded were those with heart disease, previous stroke(s), renal disease, and/or cancer. Physical examinations, biospecimen collections, and structured questionnaires were executed according to standardised protocols. We identified IHD events according to the ICD-9-CM codes 410-414 using hospitalisation records obtained from the National Health Insurance and the Death Certification Registry databases. The Cox proportional hazard model was used to estimate the hazard ratios (HRs) between SUA and IHD events. A total of 2049 subjects (1239 men, 810 women) developed IHD from baseline to Dec. 31, 2002. Men had a higher IHD incidence than did women (2.84 vs. 1.61 1/1000 person-years; p < 0.0001). The risk-factor-adjusted HRs (95% confidence-interval [CI]) for hyperuricemiae (SUA ≥ 7.0/≥ 6.0mg/dL) were 1.25 (1.11-1.40) for men and 1.19 (1.02-1.38) for women. In the low-risk population (lacking the NCEP-ATPIII metabolic syndrome components), a significant association was still observed (adjusted HR: 1.54 [1.09-2.17]).nnnCONCLUSIONnThe hyperuricemia was independently associated with the development of IHD not only in the general population but also in those without any metabolic risk factor for NCEP ATPIII. Hyperuricemia may be considered as a potential risk factor for IHD.