Jawl-Shan Hwang

Gout: an independent risk factor for all-cause and cardiovascular mortality

OBJECTIVE The relation of gout and hyperuricaemia to cardiovascular diseases has been well documented. This study investigates the survival impact of both gout and hyperuricaemia. METHODS The subjects of this study comprised participants of a health screening programme conducted by the Chang Gung Memorial Hospital in Taiwan from 2000 to 2006. The status and causes of death were ascertained by the Taiwan National Death Registry 2000-07. Cox proportional hazard model was performed to examine the association. RESULTS Among 61 527 subjects, 1383 deaths (198 cardiovascular deaths) were identified, corresponding to a crude mortality rate of 4.86 deaths per 1000 person-years. Crude mortality rates were 4.50, 5.61 and 10.46 deaths per 1000 person-years for subjects with normouricaemia, hyperuricaemia and gout, respectively. Compared with subjects with normouricaemia, the hazard ratios (HRs) of all-cause mortality were 1.46 (95% CI 1.12, 1.91) for individuals with gout and 1.07 (95% CI 0.94, 1.22) for those with hyperuricaemia, respectively, after adjustments were made for age, sex, component number of metabolic syndrome and proteinuria. The adjusted HRs of cardiovascular mortality were 1.97 (95% CI 1.08, 3.59) for individuals with gout and 1.08 (95% CI 0.78, 1.51) for those with hyperuricaemia. Moreover, the risk of all-cause or cardiovascular mortality for gout remained unchanged when limiting the data to those with an estimated glomerular filtration of >60 ml/min/1.73 m(2). CONCLUSION This study demonstrates a link of gout, not hyperuricaemia, with a higher risk of death from all causes and cardiovascular diseases.

Hyperuricaemia and accelerated reduction in renal function.

Objectives: Hyperuricaemia has been linked to reduced renal function, and evidence indicates that it may be associated with acceleration of the decline in glomerular filtration rate (GFR) and progression of chronic kidney disease (CKD). Methods: We analysed a population of subjects who had undergone serum uric acid (SUA) and serum creatinine measurements in a hospital-based cohort. Initial and final serum creatinine measurements were used to calculate the estimated glomerular filtration rate (eGFR) and the annual decline in eGFR. Cox regression was used to investigate the relationship between SUA and CKD progression. Results: A total of 63 785 subjects were enrolled in the study during a 12-year follow-up period. The mean age at the time of initial serum creatinine measurement was 50.0 ± 14.9 years. Hyperuricaemic subjects had a significantly larger annual eGFR decline, both in absolute terms (2.5 ± 9.5 mL/min/1.73 m2 per year) and as a percentage (2.8 ± 11.6% per year), as compared to the normouricaemia group (1.3 ± 9.6 mL/min/1.73 m2 per year, 1.1 ± 11.1% per year, p < 0.001). After adjustment for age, sex, status of diabetes mellitus (DM) and hypertension, baseline eGFR, azotaemia, hypercholesterolaemia, and hyperglycaemia, hyperuricaemia was associated with a hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.23–1.33, p < 0.001] for an accelerated eGFR decline ≥ 3mL/min/1.73 m2 per year and an HR of 1.52 (95% CI 1.46–1.59) for CKD progression at the end of follow-up. Conclusion: Hyperuricaemia was associated with an accelerated decline in eGFR and higher risk of CKD progression. Therefore, renal function should be monitored closely in patients with hyperuricaemia.

Gout and risk of non-alcoholic fatty liver disease

Objectives: To investigate the association between gout and non-alcoholic fatty liver disease (NAFLD). Methods: The study subjects were participants in a health-screening programme at Chang Gung Memorial Hospital from 2000 to 2006. Subjects were classified into eight groups based on serum urate (SU) level and gout status (≤ 4.9, 5.0–6.9, 7.0–8.9, and ≥ 9.0 mg/dL, without and with gout). The association between gout and NAFLD was assessed by multiple logistic regression. Results: Among a total of 54 325 subjects, 1930 (3.6%) had gout and 6169 (11.3%) had NAFLD. The prevalence of NAFLD was significantly higher in subjects with gout (23.1%, n = 445) than in those without gout (10.9%, n = 5724, p < 0.001). Among subjects with NAFLD, the severity of NAFLD was higher in gout patients. Gout was associated with an increased risk for NAFLD [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.25–1.60, p < 0.001], after adjustment for age, sex, presence of metabolic syndrome, and low estimated glomerular filtration rate (eGFR). With SU ≤ 4.9 mg/dL in the absence of gout as reference, the ORs (95% CI) for NAFLD, after adjustment for age, sex, presence of metabolic syndrome, and low eGFR, were, respectively, 2.16 (1.94–2.41), 3.98 (3.55–4.46), and 5.99 (5.19–6.90) for SU levels 2–4 in those without gout and 2.61 (1.39–4.91), 2.87 (2.04–4.04), 4.53 (3.70–5.56), and 6.31 (5.12–7.77) for SU levels 1–4 in those with gout. Conclusions: There was an independent association between gout and the risk for NAFLD. In addition, there was a dose–response relationship between SU and NAFLD in subjects with and without gout.

Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study

OBJECTIVES Hyperuricaemia has been linked to atherosclerosis; however, there is limited evidence about its association with arterial stiffness and cardiac hypertrophy, which are associated with adverse cardiovascular outcomes. We studied the association of hyperuricaemia with an increased risk of arterial stiffness and cardiac hypertrophy in a population participating in a health-screening programme. METHODS In subjects who underwent health screening from 2005 to 2007, arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), whereas cardiac hypertrophy was determined by plain chest radiography and electrocardiography. Polychotomous logistic regression was used to identify associations of hyperuricaemia with arterial stiffness and cardiac hypertrophy, after adjusting for the presence of metabolic syndrome. RESULTS Of the total 9375 subjects enrolled, 1324 (14.5%) had hyperuricaemia. Subjects with hyperuricaemia had a significantly higher baPWV [1618.8 (379.3) cm/s] than those without it [1501.8 (334.9) cm/s]. Cardiac hypertropy was observed in 1047 (11.2%) subjects. Hyperuricaemia was associated with cardiac hypertrophy with an odds ratio (OR) of 1.53 (95% CI 1.32, 1.77). Polychotomous logistic regression showed that hyperuricaemia was associated with ORs (95% CI) for coexisting abnormal baPWV and cardiac hypertrophy of 1.75 (95% CI 1.24, 2.47) and 1.41 (95% CI 1.04, 1.91) in men and women, respectively, after adjusting for age, proteinuria, high high-sensitive CRP, abnormal ankle-brachial index or a number of metabolic syndrome components present. CONCLUSION Hyperuricaemia was associated with arterial stiffness and cardiac hypertrophy. Hyperuricaemia, along with other risk factors related to atherosclerosis, could play a role in the development of cardiac hypertrophy by increasing arterial stiffness.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary

Osteoporosis is recognized as a major public health problem worldwide and in Taiwan. However, many patients with osteoporotic fractures do not receive appropriate assessments or treatments. This guideline, proposed by the Taiwanese Osteoporosis Association, is to serve as a quick reference for healthcare providers to improve the assessment of osteoporosis and development of optimal strategies for osteoporotic management in Taiwan. To review and update osteoporosis management, the guideline is constituted with Taiwan-specific osteoporosis epidemiological data, medication protocols, and the 10-year FRAX®. The guideline is based on evidence-based medicine and public health considerations. Recommendations are not limited to the reimbursement regulations permitted by the National Health Insurance of Taiwan.

Development of multiple complications in type 2 diabetes is associated with the increase of multiple markers of chronic inflammation.

Patients with type 2 diabetes (T2DM) are known at risk for developing cardiovascular disease (CVD), nephropathy, and cancer. We were interested to find out whether multiple markers associated with chronic inflammation are detectable in patients with T2DM and are increased in patients with T2DM who developed additional clinical complications. A sequence of multiple risk markers for atherogenesis, associated with chronic inflammation, was measured in patients with T2DM before and after the development of clinical complications. We found that multiple clinical complications frequently developed simultaneously in patients with T2DM. At the early stage of T2DM, only low levels and low percent elevations of multiple risk markers were detected. However, both the level and the percent elevation of these markers were found to increase with disease progression and the development of clinical complications. We believe that chronic inflammation not only contributes to the pathogenesis of T2DM but also continues to increase in T2DM patients who are developing additional clinical complications. It appears that these multiple markers are potentially useful not only for monitoring the progression of T2DM but also predicting the risk of developing macro‐ and microvascular disease, nephropathy, and cancer. J. Clin. Lab. Anal. 22:6–13, 2008.

The Asian Federation of Osteoporosis Societies' call to action to improve the undertreatment of osteoporosis in Asia

Osteoporosis and its associated fractures lead to significant morbidity and mortality worldwide. Asia is not exempt, as it has been estimated that over 50% of all the hip fractures in the world will occur in Asia by 2050 [1]. A recent review estimated that around 30% of the hip fractures occurring worldwide will arise in Asian populations, most notably in China [2], due to an increasingly ageing population. The age-adjusted incidence of hip fracture among men and women in China [2,3], Japan [2], and Thailand [4] are increasing, with a possible stabilization of the rates in Hong Kong and Singapore [2]. The increased mortality following osteoporotic fractures has also been shown in Asian populations. A multicentre survey from mainland China found that the mortality was doubled after osteoporotic vertebral and hip fractures compared to that of the healthy population [5]. The 1-year mortality after a hip and vertebral fracture was 3.8% and 3.1% respectively, compared to 1.6% in the nonfracture population. Overall, the 5-year mortality was 16.9% [5]. In Taiwan, the 1-year mortality after a low-energy trauma hip fracture was found to be 12.4% [6]. The 1-year mortality rate after hip fracture was 23.9% in Korean nursing home residents [7]. Morbidity with impaired self-care ability was also high, with 40.6% affected after a hip fracture in the aforementioned study in mainland China [5]. The risk of a second osteoporotic fracture following the first osteoporotic fracture is increased by up to 4 times compared to those who have not yet had a fracture [8]. Thus, treating these high-risk patients should be a key priority. Despite the significant mortality and morbidity following osteoporotic fractures, there is a lack of recognition of the importance of osteoporosis, with very few Asian countries making osteoporosis one of their national health priorities [9]. The ability to diagnose osteoporosis can pose a challenge in Asia. Many countries in Asia have predominant rural populations where there is difficulty in getting access to health care professionals who are knowledgeable about osteoporosis. In addition, access to bone mineral density measurements with dual-energy X-ray absorptiometry (DXA) is highly variable, with many Asian countries having less than 1 DXA machine per million population [9], when the recommendation is 10.6 DXA units per million of the general population [10]. Antiosteoporosis medication (AOM) have been shown to be very effective in significantly reducing future osteoporotic fractures [11]. However, even when osteoporosis has been identified after a fragility fracture, a treatment gap remains. The low rate of

Subclinical hypothyroidism and metabolic risk factors association: A health examination-based study in northern Taiwan

Background Subclinical hypothyroidism (SCH) is defined as elevation in serum thyroid-stimulating hormone (TSH) levels despite normal serum levels of free thyroxine. It remains controversial whether people with SCH have higher total cholesterol and low-density lipoprotein cholesterol levels compared to normal-thyroid subjects. The aim of this study was to assess the metabolic risk factors for SCH. Methods Subjects were recruited from the health examination center of Chang Gung Memorial Hospital, Linkou, from January 1, 2010 to December 31, 2011. This was a cross-sectional review of medical records. The subjects were ethnic Taiwanese residents without known thyroid disease at baseline. Results A total of 22,324 subjects received annual health examination at Chang Gung Memorial Hospital from 2010 to 2011. Among them, 15,943 subjects were included as the normal thyroid group (NG), and 203 subjects (101 men and 102 women) met the criteria for SCH. The prevalence of metabolic syndrome (MetS) in the NG was 26.2% in men and 18.7% in women, whereas that in the SCH group was 39.6% in men and 29.4% in women. Women in the SCH group showed significantly higher cholesterol, triglyceride, non-high density lipoprotein (HDL) and cholesterol/HDL levels than those in the NG (p < 0.05). Conclusion Because SCH is more prevalent in women and the risk increases with age, greater attention to the risk of MetS development is warranted. As for men, regardless of thyroid function, the risk of MetS development with age still warrants attention. Thus, our data suggest that national guidelines for screening for thyroid disease using serum TSH levels in the elderly are mandatory.

Association of small dense lowdensity lipoprotein cholesterol in type 2 diabetics with coronary artery disease.

Background: The risk of coronary artery disease (CAD) increases two- to fourfold in diabetes. Small dense low-density lipoprotein (sdLDL) particles have been linked to an increased risk for CAD. In this study, we sought to compare the sdLDL cholesterol (sdLDL-C) level between the healthy control group and diabetics with CAD in the Taiwanese population. Methods: Serum specimens were collected from healthy females and males of various age groups (n = 294), type 2 diabetics (DM) without complications (n = 113), and patients having DM with CAD (DM-CAD) (n = 46). The commercial kit was used for the measurement of sdLDL-C level, which employs a simpler method. After heparin-magnesium precipitation of lipoproteins with density <1.044 g/ml, sdLDL (density = 1.044-1.063 g/ml) remained in the supernatant and this sdLDL-C was measured using an automated chemistry analyzer. Results: The sdLDL-C level was significantly higher in males than in females (p < 0.001) and there was an age effect on sdLDL-C (p < 0.001). The DM-CAD group had significantly higher sdLDL-C levels than the healthy control group (p < 0.001), but there was no statistical difference in the LDL-C level between DM-CAD group and the healthy control group. In addition, only individuals having both high LDL-C and sdLDL-C levels had a higher risk for DM-CAD, compared to those with low LDL-C levels and low sdLDL-C levels [Odds Ratio (OR) 4.97; 95% Confidence Interval (CI) 1.96-12.57; p = 0.001]. Conclusions: Our data suggest that the sdLDL-C level together with the LDL-C level are better risk assessment markers for type 2 diabetics with CAD than the LDL-C level alone.