Publications by authors named "Kuo-Liong Chien"

261 Publications

Lipid biomarkers and Cancer risk - a population-based prospective cohort study in Taiwan.

Lipids Health Dis 2021 Oct 10;20(1):133. Epub 2021 Oct 10.

Department of Family Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, Taipei City, 10449, Taiwan.

Background: Blood lipids are essential components for cellular growth. An inverse association between serum lipid levels and risk of cancer has led to a controversy among previous studies. The aim of this prospective cohort study was to investigate the association between blood lipids change and risk of cancer incidence.

Methods: A cohort of 4130 Taiwanese adults from the Taiwanese Survey on the Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia database underwent repeated examinations in 2002 and 2007. Six groups were established based on the combined baseline (lower/higher) and interval change (decreasing/stable/increasing) in plasma lipid levels. Multivariable Cox proportional hazard model was used to investigate the relationship between lipids change and all-cause cancer incidence.

Results: Two hundred and forty cancer events developed over a median follow-up of 13.4 years. Comparing these with individuals with decreasing lower-baseline lipid levels, cancer risk reduction was demonstrated in those with increasing lower-baseline total cholesterol (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.27 to 0.85), low-density lipoprotein cholesterol (LDL-C; aHR, 0.56; 95% CI, 0.35 to 0.92), and non-high-density lipoprotein cholesterol (non-HDL-C) (aHR, 0.54; 95% CI, 0.31 to 0.92) levels. A decreased risk for cancer incidence also presented in participants with stable lower-baseline, decreasing and increasing higher-baseline LDL-C levels, and with decreasing and stable higher-baseline non-HDL-C levels.

Conclusions: The interval decline in lower-baseline total cholesterol, LDL-C, and non-HDL-C levels was linked to a higher risk for all-cause cancer incidence. More attention to a potential cancer risk may be warranted for an unexplained fall in serum lipids.
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http://dx.doi.org/10.1186/s12944-021-01570-1DOI Listing
October 2021

Prior beta-blocker treatment improves outcomes in out-of-hospital cardiac arrest patients with non-shockable rhythms.

Sci Rep 2021 Aug 19;11(1):16804. Epub 2021 Aug 19.

Department of Emergency Medicine, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Rd., Taipei, 100, Taiwan.

The prognosis of out of cardiac arrest is poor and most cardiac arrest patients suffered from the non-shockable rhythm especially in patients without pre-existing cardiovascular diseases and medication prescription. Beta-blocker (ß-blocker) therapy has been shown to improve outcomes in cardiovascular diseases such as heart failure, ischemia related cardiac, and brain injuries. Therefore, we investigated whether prior ß-blockers use was associated with reduced mortality in patients with cardiac arrest and non-shockable rhythm. We conducted a population-based retrospective cohort study using multivariate propensity score-based regression to control for differences among patients with cardiac arrest. A total of 104,568 adult patients suffering a non-traumatic and non-shockable rhythm cardiac arrest between 2005 and 2011 were identified. ß-blocker prescription at least 30 days prior to the cardiac arrest event was defines as the ß-blockers group. We chose 12.5 mg carvedilol as the cut-off value and defined greater or equal to carvedilol 12.5 mg per day and its equivalent dose as high-dose group. After multivariate propensity score-based logistic regression analysis, patients with prior ß-blockers use were associated with better 1-year survival [adjusted odds ratio (OR), 1.15, 95% confidence interval (CI) 1.01-1.30; P = 0.031]. Compared to non-ß-blocker use group and prior low-dose ß-blockers use group, prior high-dose ß-blockers use group was associated with higher mechanical ventilator wean success rate (adjusted OR 1.19, 95% CI 1.01-1.41, P = 0.042). In conclusion, prior high dose ß-blockers use was associated with a better 1-year survival and higher weaning rate in patients with non-shockable cardiac arrest.
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http://dx.doi.org/10.1038/s41598-021-96070-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377081PMC
August 2021

Clinical Significance of Ventricular Tachyarrhythmias in Patients Undergoing Valve Replacement: A Nationwide Population-Based Study.

Front Cardiovasc Med 2021 15;8:676897. Epub 2021 Jul 15.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

The clinical significance and outcomes of ventricular tachyarrhythmias (VTa) in patients undergoing valve replacement have rarely been reported. This study aimed to investigate the incidence and outcome of VTa after surgical valve replacement. We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,212 patients were selected after 1:1 propensity-score matching based on the type of prosthetic valve used (mechanical vs. bioprosthetic). Various outcomes during long-term follow-up were analyzed. After a median follow-up period of 59.6 months, the crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased after surgery. Furthermore, the occurrences of VTa after valve replacement significantly increased the risk of cardiovascular (CV) death ( < 0.001, HR 1.67, 95% CI 1.41-1.96), stroke- ( < 0.001, HR 1.66, 95% CI 1.37-2.01), atrial fibrillation- ( < 0.001, HR 2.80, 95% CI 2.42-3.24), and congestive heart failure-related hospitalization ( < 0.001, HR 2.61, 95% CI 2.30-2.95). Among patients with VTa, all-cause mortality ( = 0.001, HR 0.49, 95% CI 0.32-0.75) and CV death ( = 0.047, HR 0.58, 95% CI 0.34-0.99) in those with implantable cardioverter-defibrillator (ICD) implantation were lower than those without. The crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased during follow-up. The presence of VTa after surgical valve replacement increases hospitalization and CV death, while ICD implantation reduced the mortality rate in these patients.
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http://dx.doi.org/10.3389/fcvm.2021.676897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319543PMC
July 2021

Association between type 2 diabetes and osteoporosis risk: A representative cohort study in Taiwan.

PLoS One 2021 13;16(7):e0254451. Epub 2021 Jul 13.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.

Although previous studies have investigated the relationship between fracture risk and type 2 diabetes (T2D), cohort studies that estimate composite osteoporosis risk are lacking. This retrospective cohort study sought to determine the risk of osteoporosis in Taiwanese patients with T2D. Patients diagnosed with T2D between 2002 and 2015 identified through the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia were included. A total of 1690 men and 1641 women aged ≥40 years linked to the National Health Insurance Research Database (NHIRD) were followed up to the end of 2015 to identify the incidences of osteoporosis through ICD9-CM codes for osteoporosis or osteoporotic fractures or usage of anti-osteoporotic agents according to Anatomical Therapeutic Chemical codes determined from NHIRD. The person year approach and Kaplan-Meier analysis were then used to estimate the incidences and cumulative event rates, whereas the Cox proportional hazard model was used to calculate adjusted hazard ratios (HR) for osteoporosis events. A total of 792 new osteoporosis events were documented over a median follow-up duration of 13.6 years. Participants with T2D had higher osteoporosis risk [adjusted HR: 1.37, 95% confidence interval (CI): 1.11-1.69] compared with those without T2D. Subgroup analyses revealed that age had a marginally significant effect, indicating that T2D had a more pronounced effect on osteoporosis risk in younger population (<65 years old). No difference was found between patients stratified according to sex. In conclusion, T2D was significantly associated with increased osteoporosis risk, especially in younger participants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254451PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277062PMC
July 2021

Muscle relaxant use and the associated risk of incident frailty in patients with diabetic kidney disease: a longitudinal cohort study.

Ther Adv Drug Saf 2021 11;12:20420986211014639. Epub 2021 Jun 11.

Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County.

Background: Patients with diabetic kidney disease (DKD) are at an increased risk of frailty. The exposure to muscle relaxants frequently leads to adverse effects despite their modest therapeutic efficacy, but whether muscle relaxants predispose users to frailty remains unclear.

Methods: Patients with DKD from a population-based cohort, the Longitudinal Cohort of Diabetes Patients, were identified between 2004 and 2011 ( = 840,000). Muscle relaxant users were propensity score-matched to never-users in a 1:1 ratio based on demographic features, comorbidities, outcome-relevant medications, and prior major interventions. Incident frailty, the study endpoint, was measured according to a modified FRAIL scale. We used Kaplan-Meier analyses and Cox proportional hazard regression to analyze the association between cumulative muscle relaxant use (⩾ 28 days) and the risk of incident frailty.

Results: Totally, 11,637 users and matched never-users were enrolled, without significant differences regarding baseline clinical features. Cox proportional hazard regression showed that patients with DKD and received muscle relaxants had a significantly higher risk of incident frailty than never-users [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.04-1.53]. This increase in frailty risk paralleled that in cumulative muscle relaxant dosages (quartile 1 2 3 4, HR 0.91 1.22 1.38 1.45,  = 0.0013 for trend) and in exposure durations (quartile 1 2 3 4, HR 1.12 1.33 1.23 1.34,  = 0.0145 for trend) of muscle relaxants.

Conclusion: We found that cumulative muscle relaxant exposure might increase frailty risk. It is prudent to limit muscle relaxant prescription in patients with DKD.

Plain Language Summary: Frailty denotes a degenerative feature that adversely influences one's survival and daily function. Patients with diabetes and chronic kidney disease are at a higher risk of developing frailty, but whether concurrent medications, especially muscle relaxants, aggravate this risk remains undefined. In this population-based study including 11,637 muscle relaxant users and matched never-users with diabetic kidney disease, we used a renowned frailty-assessing tool, FRAIL scale, to assess frailty severity and examined the incidence of frailty brought by muscle relaxant exposure. We found that users exhibited a 26% higher risk of developing incident frailty compared with never-users, and the probability increased further if users were prescribed higher doses or longer durations of muscle relaxants. We concluded that in those with diabetic kidney disease, cumulative muscle relaxant use was associated with a higher risk of incident frailty, suggesting that moderation of muscle relaxant use in this population can be of potential importance.
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http://dx.doi.org/10.1177/20420986211014639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202305PMC
June 2021

Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease.

BMC Geriatr 2021 06 7;21(1):349. Epub 2021 Jun 7.

Nephrology division, Department of Internal Medicine, National Taiwan University Hospital Yunlin branch, Yunlin county, Taiwan.

Background: Patients with diabetic mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of urinary tract infection (UTI) due to their altered immunological integrity. These patients are similarly prone to developing frailty, a state of cumulative health deficits involving multiple domains and leading to adverse outcomes. Whether frailty predisposes affected individuals to UTI among patients with DM and CKD remains unclear.

Methods: A population-based cohort of patients with DM and CKD (n = 79,887) were assembled from the Longitudinal Cohort of Diabetes Patients, with their baseline frailty status measured by a  modified FRAIL scale. We analyzed their risk of developing UTI depending on their severity of frailty, after accounting demographic profiles, lifestyle factors, comorbidities, concurrent medications, and major interventions. A secondary analysis focused on the risk of urosepsis related to frailty.

Results: Among all participants, 36.1 %, 50.3 %, 12.8 %, and 0.8 % did not have or had 1, 2, and ≥ 3 FRAIL items, respectively, at baseline. After 3.51 years, 11,175 UTI events occurred. Kaplan-Meier analysis showed that participants with DM, CKD and an increasing number of FRAIL items had successively higher incidence of UTI than those without any FRAIL items (log rank p < 0.001). Cox proportional hazard modeling revealed that after accounting for all confounders, those with more severe frailty exhibited a significantly higher risk of incident UTI (for groups of 1, 2, and ≥ 3 FRAIL items, hazard ratio 1.19, 1.24, and 1.43, respectively; all p < 0.001) than those without. An 11 % risk elevation for UTI could be observed for every FRAIL item increase. Participants with more severe frailty exhibited a trend of having higher risk of urosepsis as well.

Conclusions: Having frailty predicted a higher risk of developing UTI in the future in patients with DM and CKD. It would be prudent to screen for frailty in these patients and provide optimal frailty-directed management to attenuate their risk of UTI and improve their outcomes.
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http://dx.doi.org/10.1186/s12877-021-02299-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186134PMC
June 2021

Gender difference in metabolic syndrome and incident colorectal adenoma: A prospective observational study (KCIS No.42).

Medicine (Baltimore) 2021 Jun;100(22):e26121

Department of Family Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

Abstract: This community-based study aimed to elucidate whether there is a gender difference in the effect of metabolic syndrome (MetS) and its individual components on an elevated risk for incident colorectal adenoma.A prospective cohort study was conducted by enrolling 59,767 subjects aged 40 years or older between 2001 and 2009 in Keelung, Taiwan, to test this hypothesis, excluding those with a prior history of colorectal cancer and those with colorectal cancer diagnosed at the first screening. Cox proportional hazards regression models were used to assess the effect of MetS in terms of a dichotomous classification, each individual component and the number of components for males and females.Colorectal adenoma was present in 2.7% (n = 652) of male participants and 1.1% (n = 403) of female participants. The prevalence rate of MetS was 26.7% and 23.3% for males and females, respectively. The effect of MetS on colorectal adenoma was statistically significant and similar for the 2 genders, with an adjusted hazard ratio (aHR) of 1.33 (95% CI: 1.13-1.58) in males and 1.33 (95% CI: 1.06-1.66) in females after adjustment for confounders. However, MetS led to higher risk of advanced colorectal adenoma in men than in women. Regarding the effect of each component of MetS on colorectal adenoma, abnormal waist circumference and hypertriglyceridemia led to an elevated risk of colorectal adenoma in both genders. A rising risk of colorectal adenoma among females was noted in those with a moderately higher level of glycemia (100-125 mg/dL, aHR = 1.44, 95% CI: 1.12-1.85). Hypertriglyceridemia and high blood pressure were associated with an increased risk of advance colorectal adenoma in males.Both male and female subjects with MetS had a higher risk of colorectal adenoma. The contributions from individual components of MetS varied by gender. These findings suggest that the possible risk reduction of colorectal adenoma through metabolic syndrome-based lifestyle modifications may differ between genders.
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http://dx.doi.org/10.1097/MD.0000000000026121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183717PMC
June 2021

Urinary sodium excretion and the risk of CVD: a community-based cohort study in Taiwan.

Br J Nutr 2021 May 27:1-12. Epub 2021 May 27.

Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City, 10002, Taiwan.

Urinary Na excretion is a potential risk factor for CVD. However, the underlying biological mechanisms and effects of salt sensitivity are unclear. The purpose of this study was to characterise the relative contribution of biological factors to the Na-CVD association. A total of 2112 participants were enrolled in this study. Structured questionnaires and blood and urine samples were obtained. Twenty-four-hour Na excretion was estimated using a single overnight urine sample. Hypertension, the metabolic syndrome and overweight status were considered to indicate salt sensitivity. Cox proportional hazard models were used to investigate the effects of salt sensitivity on urinary Na excretion and CVD risk. The traditional mediation approach was used to calculate the proportion of mediation. The mean age (sd) of the 2112 participants was 54·5 (sd 12·2) years, and they were followed up for a mean of 14·1 (sd 8·1) years. Compared with those in the lowest quartile, the highest baseline urinary Na excretion (>4·2 g/24 h) was associated with a 43 % higher CVD risk (hazard ratio, 1·43; 95 % CI 1·02, 1·99). Participants with high urinary Na excretion, hypertension or the metabolic syndrome had a significantly high risk of CVD. The carotid intima-media thickness had the largest mediating effect (accounting for 35 % of the Na-CVD association), followed by systolic blood pressure (BP) (33 %), left ventricular mass (28 %) and diastolic BP (14 %). Higher urinary Na excretion increased the risk of CVD, which was explained largely by carotid media-thickness and systolic BP.
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http://dx.doi.org/10.1017/S0007114521001768DOI Listing
May 2021

Novel model-based point scoring system for predicting stroke risk in atrial fibrillation patients: Results from a nationwide cohort study with validation.

Int J Cardiol Heart Vasc 2021 Jun 28;34:100787. Epub 2021 Apr 28.

Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The stroke risk scoring system for atrial fibrillation (AF) patients can vary considerably based on patients' status while receiving ablation. This study aimed to demonstrate a novel scoring system for stroke risk stratification based on the status of catheter ablation.

Methods: First, 787 patients with AF undergoing ablation were matched according to age, sex, and underlying diseases with the same number of patients not undergoing ablation using the propensity-score (PS)-matched cohort. Multivariate Cox model-derived coefficients were used to construct a simple point-based clinical model using the PS-matched cohort. Thereafter, the novel model (AF-CA-Stroke score) was validated in a nationwide AF cohort.

Results: The AF-CA-Stroke score was calculated based on age (point = 5), ablation status (point = 4), prior history of stroke (point = 4), chronic kidney disease (point = 2), diabetes mellitus (point = 1), and congestive heart failure (point = 1). Risk function to predict the 1-, 5-, 10-year absolute stroke risks was reported. The estimated area under the receive operating characteristic curve of the AF-CA-Stroke score in the PS-matched cohort was 0.845 (95% confidence interval: 0.824-0.865) to predict long-term stroke. A validation study showed that discrimination abilities in the AF-CA-Stroke scores were significantly higher than those in the CHADS/CHADSVASc scores. The best cut-off value of the AF-CA-Stroke score to predict future strokes was ≥ 5.

Conclusions: This novel model-based point scoring system effectively identifies stroke risk using clinical factors and AF ablation status of patients with AF. Various age stratifications and AF ablation should be considered in AF management.
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http://dx.doi.org/10.1016/j.ijcha.2021.100787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102915PMC
June 2021

The risk trajectory of different cardiovascular morbidities associated with chronic kidney disease among patients with newly diagnosed diabetes mellitus: a propensity score-matched cohort analysis.

Cardiovasc Diabetol 2021 04 24;20(1):86. Epub 2021 Apr 24.

Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: Chronic kidney disease (CKD) introduces an increased cardiovascular risk among patients with diabetes mellitus (DM). The risk and tempo of cardiovascular diseases may differ depending upon their type. Whether CKD differentially influences the risk of developing each cardiovascular morbidity in patients with newly diagnosed DM remains unexplored.

Methods: We identified patients with incident DM from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort (n = 429,616), and uncovered those developing CKD after DM and their propensity score-matched counterparts without. After follow-up, we examined the cardiovascular morbidity-free rates of patients with and without CKD after DM, followed by Cox proportional hazard regression analyses. We further evaluated the cumulative risk of developing each outcome consecutively during the study period.

Results: From LCDP, we identified 55,961 diabetic patients with CKD and matched controls without CKD. After 4.2 years, patients with incident DM and CKD afterward had a significantly higher risk of mortality (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.06-1.14), heart failure (HF) (HR 1.282, 95% CI 1.19-1.38), acute myocardial infarction (AMI) (HR 1.16, 95% CI 1.04-1.3), and peripheral vascular disease (PVD) (HR 1.277, 95% CI 1.08-1.52) compared to those without CKD. The CKD-associated risk of mortality, HF and AMI became significant soon after DM occurred and remained significant throughout follow-up, while the risk of PVD conferred by CKD did not emerge until 4 years later. The CKD-associated risk of ischemic, hemorrhagic stroke and atrial fibrillation remained insignificant.

Conclusions: The cardiovascular risk profile among incident DM patients differs depending on disease type. These findings can facilitate the selection of an optimal strategy for early cardiovascular care for newly diagnosed diabetic patients.
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http://dx.doi.org/10.1186/s12933-021-01279-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070330PMC
April 2021

Association between dietary flavonoid intakes and C-reactive protein levels: a cross-sectional study in Taiwan.

J Nutr Sci 2021;10:e15. Epub 2021 Mar 4.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.

Although the intake of specific flavonoid-rich foods may reduce C-reactive protein (CRP) levels, the association between dietary flavonoid intakes and CRP is inconsistent. We aim to describe dietary flavonoid intakes in a Taiwanese nationally representative sample and to investigate the association between flavonoid intakes and CRP. We conducted a cross-sectional study based on 2592 adults from the Nutrition and Health Survey in Taiwan 2005-8. Flavonoid intakes were estimated by linking the 24-h dietary recall with the U.S. Department of Agriculture flavonoid database and divided into quartiles. Adjusted estimates of the flavonoid intakes for the continuous and binary (elevated CRP: >0⋅3 mg/dl) variables were performed by using general linear and logistic regression. We found that tea, orange, tofu and sweet potato leaves/water spinach constituted the major food items of the total flavonoid intake. The total flavonoid intake was lower among women and elderly. Compared with the lowest total flavonoid intake quartile, participants in higher quartiles were associated with a lower CRP status (adjusted odds ratio (OR): 0⋅61, 95 % confidence interval (CI): 0⋅44-0⋅86 for the highest quartiles). The trends were similar for flavonol and flavan-3-ol intakes. Compared with non-consumers, tea consumers were likely to have a lower CRP status (adjusted OR: 0⋅74, 95 % CI: 0⋅57-0⋅97). In brief, a higher total flavonoid intake and tea consumption were inversely associated with CRP levels, indicating that a high-flavonoid diet may contribute to anti-inflammatory effects. A Taiwanese flavonoid content table is necessary for conducting further studies related to flavonoids in Taiwan.
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http://dx.doi.org/10.1017/jns.2021.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057367PMC
March 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

Adolescent Tri-ponderal Mass Index Growth Trajectories and Incident Diabetes Mellitus in Early Adulthood.

J Clin Endocrinol Metab 2021 07;106(8):e2919-e2927

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Purpose: Studies have reported the influence of adolescent obesity on development of adult diabetes, but the effect of the growth pattern during this period has rarely been explored. Also, the tri-ponderal mass index (TMI) was thought to be a better estimation of adolescent body fat levels than the body mass index (BMI), so we sought to investigate whether growth trajectories derived by these two indices could predict incident diabetes.

Methods: We conducted a study by using the Taipei City Hospital Radiation Building Database, a longitudinal cohort established in 1996. Physical exam results including blood test results were collected annually and the BMI z-score/TMI growth trajectory groups during 13 to 18 years of age were identified using growth mixture modeling. A Cox proportional hazard model for incident diabetes was used to examine the risk of baseline obese status and different BMI/TMI growth trajectories.

Results: Five growth trajectory groups were identified for the BMI z-score and the TMI. During approximately 20 400 person-years follow-up, 33 of 1387 participants developed diabetes. Baseline obesity defined by the BMI z-score and the TMI were both related to adult diabetes. The persistent increase TMI growth trajectory exhibited a significantly increased risk of diabetes after adjusting for baseline obese status and other correlated covariates (hazard ratio: 2.85, 95% confidence interval: 1.01-8.09). There was no association between BMI growth trajectory groups and incident diabetes.

Conclusions: A specific TMI growth trajectory pattern during adolescence might be critical for diabetes prevention efforts.
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http://dx.doi.org/10.1210/clinem/dgab235DOI Listing
July 2021

Association of baseline as well as change in lipid levels with the risk of cardiovascular diseases and all-cause deaths.

Sci Rep 2021 04 1;11(1):7381. Epub 2021 Apr 1.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, Room 517, No. 17, Xu-Zhou Rd., Taipei City, 10055, Taiwan.

High baseline atherogenic lipid level has been an established risk factor for the risk of cardiovascular events. Evidence concerning the role of lipid changes in cardiovascular and death risks are inconclusive. A cohort study was conducted based on the Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (n = 4072, mean 44.8 years, 53.5% women) assessing lipid levels of the participants repeatedly measured in 2002 and 2007. Combined baseline and changes in lipid levels were classified into four groups-stable or decreasing lipid changes and increasing lipid changes with low- and high-risk baseline lipid levels. Developing cardiovascular events (n = 225) and all-cause deaths (n = 345) were ascertained during a median follow-up of 13.3 years. Participants with increasing and higher total cholesterol level were more likely to develop cardiovascular risks. Similar patterns for cardiovascular events were observed across other lipid profile changes. However, participants with increasing total cholesterol, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) levels were more likely to be at a lower risk for all-cause deaths. Baseline and changes in total cholesterol, triglycerides, and LDL-C levels were positively associated with the risk of cardiovascular diseases, whereas baseline and changes in total cholesterol and LDL-C and non-HDL-C levels were inversely associated with all-cause deaths.
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http://dx.doi.org/10.1038/s41598-021-86336-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016969PMC
April 2021

Frailty is associated with a higher risk of developing delirium and cognitive impairment among patients with diabetic kidney disease: A longitudinal population-based cohort study.

Diabet Med 2021 Jul 5;38(7):e14566. Epub 2021 Apr 5.

Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan.

Aims: Delirium, a form of acute brain failure, exhibits a high incidence among older adults. Recent studies have implicated frailty as an under-recognized complication of diabetes mellitus. Whether the presence of frailty increases the risk of delirium/cognitive impairment among patients with diabetic kidney disease (DKD) remains unclear.

Methods: From the longitudinal cohort of diabetes patients (LCDP) (n = 840,000) in Taiwan, we identified adults with DKD, dividing them into those without and with different severities of frailty based on a modified FRAIL scale. Cox proportional hazard regression was utilized to examine the frailty-associated risk of delirium/cognitive impairment, identified using approaches validated by others.

Results: Totally 149,145 patients with DKD (mean 61.0 years, 44.2% female) were identified, among whom 31.0%, 51.7%, 16.0% and 1.3% did not have or had 1, 2 and >2 FRAIL items at baseline. After 3.68 years, 6613 (4.4%) developed episodes of delirium/cognitive impairment. After accounting for demographic/lifestyle factors, co-morbidities, medications and interventions, patients with DKD and 1, 2 and >2 FRAIL items had a progressively higher risk of developing delirium/cognitive impairment than those without (for those with 1, 2 and >2 items, hazard ratio 1.18, 1.26 and 1.30, 95% confidence interval 1.08-1.28, 1.14-1.39 and 1.10-1.55, respectively). For every FRAIL item increase, the associated risk rose by 9%.

Conclusions: Frailty significantly increased the risk of delirium/cognitive impairment among patients with DKD. Frailty screening in these patients may assist in delirium risk stratification.
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http://dx.doi.org/10.1111/dme.14566DOI Listing
July 2021

Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan.

J Hepatol 2021 07 6;75(1):132-141. Epub 2021 Mar 6.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background & Aims: Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period.

Methods: Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates.

Results: Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively.

Conclusions: Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

Lay Summary: Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.
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http://dx.doi.org/10.1016/j.jhep.2021.02.029DOI Listing
July 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 05 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death.

Sci Rep 2021 Feb 11;11(1):3677. Epub 2021 Feb 11.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 533, No. 17, Hsuchow Road, Taipei, 100, Taiwan.

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.
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http://dx.doi.org/10.1038/s41598-021-83118-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878780PMC
February 2021

Association between metabolically healthy obesity/overweight and cardiovascular disease risk: A representative cohort study in Taiwan.

PLoS One 2021 1;16(2):e0246378. Epub 2021 Feb 1.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.

Objectives: To investigate the relationship between metabolically healthy obesity and cardiovascular disease risk in Taiwanese individuals.

Methods: Taiwanese individuals were recruited from a nationwide, representative community-based prospective cohort study and classified according to body mass index as follows: normal weight (18.5-23.9 kilogram (kg)/meter(m)2) and obesity/overweight (≥24 kg/m2). Participants without diabetes, hypertension, and hyperlipidemia and who did not meet the metabolic syndrome without waist circumference criteria were considered metabolically healthy. The study end points were cardiovascular disease morbidity and mortality. Multivariable adjusted hazard ratios and 95% confidence intervals were obtained from a Cox regression analysis.

Results: Among 5 358 subjects (mean [standard deviation] age, 44.5 [15.3] years; women, 48.2%), 1 479 were metabolically healthy with normal weight and 491 were metabolically healthy with obesity. The prevalence of metabolically healthy obesity/overweight was 8.6% in the Taiwanese general population, which included individuals who were >20 years old, not pregnant, and did not have CVD (n = 5,719). In the median follow-up period of 13.7 years, 439 cardiovascular disease events occurred overall and 24 in the metabolically healthy obesity group. Compared with the reference group, the metabolically healthy obesity group had a significantly higher cardiovascular disease risk (adjusted hazard ratio: 1.74, 95% confidence interval: 1.02, 2.99).

Conclusions: Individuals with metabolically healthy obesity have a higher risk of cardiovascular disease and require aggressive body weight control for cardiovascular disease control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246378PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850496PMC
August 2021

Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study.

Acta Derm Venereol 2021 Feb 11;101(2):adv00390. Epub 2021 Feb 11.

Department of Dermatology, Taipei City Hospital, Taipei City, Taiwan.

The safety of ultraviolet B (UVB) phototherapy with respect to cutaneous carcinogenesis has not been established for patients with chronic kidney disease. To investigate this issue, a nationwide cohort study of 10,805 patients with advanced chronic kidney disease was conducted using data from the National Health Insurance of Taiwan, the Taiwan Cancer Registry, and the national death registry. After a median follow-up of 75 months, 16 of 2,161 patients in the UVB group and 63 of 8,644 patients in the non-UVB group developed skin cancers. Compared with the non-UVB group, patients in the UVB group did not show an increased risk of skin cancer (hazard ratio 1.066; 95% confidence interval 0.584-1.944), non-melanoma skin cancer (hazard ratio 1.067; 95% confidence interval 0.571-1.996), or cutaneous melanoma (hazard ratio 1.009; 95% confidence interval 0.115-8.879). In addition, patients who received more UVB phototherapy did not show an increased risk of skin cancer. UVB phototherapy appears to be a safe treatment for uraemic pruritus in patients with chronic kidney disease.
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http://dx.doi.org/10.2340/00015555-3758DOI Listing
February 2021

Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial.

Ren Fail 2021 Dec;43(1):141-148

Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.

Background: Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations.

Methods: This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models.

Results: Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4,  < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01,  = .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3,  = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0,  = .001). Dietary phosphorus intake was not related to cFGF23.

Conclusions: Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.
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http://dx.doi.org/10.1080/0886022X.2020.1870138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808738PMC
December 2021

Frailty modifies the association between opioid use and mortality in chronic kidney disease patients with diabetes: a population-based cohort study.

Aging (Albany NY) 2020 11 7;12(21):21730-21746. Epub 2020 Nov 7.

Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan.

The prevalence of chronic pain in patients with chronic kidney disease (CKD) and diabetes mellitus is high and correlates with higher frailty risk, but satisfactory pain control frequently fails, necessitating opioid initiation. We aimed to examine whether opioid use affected their outcomes and whether such a relationship was modified by frailty. From the longitudinal cohort of diabetes patients (n = 840,000), we identified opioid users with CKD (n = 26,029) and propensity score-matched them to opioid-naïve patients in a 1:1 ratio. We analyzed the associations between opioid use and long-term mortality according to baseline frailty status, defined by the modified FRAIL scale. Among all, 20.3% did not have any FRAIL items, while 57.2%, 20.6%, and 1.9% had 1, 2, and at least 3 positive FRAIL items, respectively. After 4.2 years, 16.4% died. Cox proportional hazard regression showed that opioid users exhibited an 18% higher mortality risk (HR 1.183, 95% CI 1.13-1.24) with a dose- and duration-responsive relationship, compared to opioid-naive ones. Furthermore, the mortality risk posed by opioids was observed only in CKD patients without frailty but not in those with frailty. In conclusion, opioid use increased mortality among patients with CKD, while this negative outcome influence was not observed among frail ones.
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http://dx.doi.org/10.18632/aging.103978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695426PMC
November 2020

Combined healthy lifestyle factors are more beneficial in reducing cardiovascular disease in younger adults: a meta-analysis of prospective cohort studies.

Sci Rep 2020 10 23;10(1):18165. Epub 2020 Oct 23.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 517, No. 17, Xu-Zhou Rd., Taipei, 10055, Taiwan, ROC.

To determine the association between combined lifestyle factors, including healthy diet, moderate alcohol consumption, non-smoking, physical activity, and optimal weight, and cardiovascular disease (CVD) risk among younger and older adults. We conducted a literature search using PubMed, EMBASE, Cochrane Library, and EBSCO databases up to November 30, 2019 and performed dose-response analysis, subgroup analysis and meta-regression with odds ratios and 95% confidence intervals (CIs). Twenty cohort studies involving 1,090,261 participants with 46,288 cardiovascular events and mean follow-up duration of 12.33 years were included. Compared with the group with the lowest number of healthy lifestyle factors, the group with the highest number had lower CVD risk [pooled hazard ratio, 0.37 (95% CI 0.31-0.43)]. With age as an effect modifier, the lifetime risk of CVD was 0.31 (95% CI 0.24-0.41) at age 37.1-49.9 years, 0.36 (95% CI 0.30-0.45) at age 50.0-59.9 years and 0.49 (95% CI 0.38-0.63) at age 60.0-72.9 years. The hazard ratio of CVD significantly increased from 37.1 to 72.9 years of age [slope in multivariate meta-regression: 0.01 (95% CI < 0.001-0.03; p = 0.042)]. Younger adults have more cardiovascular benefits from combined healthy lifestyle factors.
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http://dx.doi.org/10.1038/s41598-020-75314-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584648PMC
October 2020

Dietary Sodium Intake and Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-Analysis.

Nutrients 2020 Sep 25;12(10). Epub 2020 Sep 25.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, No.17, Xu-Zhou Rd.,Taipei City 10055, Taiwan.

Dietary sodium intake has received considerable attention as a potential risk factor of cardiovascular disease. However, evidence on the dose-response association between dietary sodium intake and cardiovascular disease risk is unclear. Embase and PubMed were searched from their inception to 17 August 2020 and studies that examined the association between sodium intake and cardiovascular disease in adolescents were not included in this review. We conducted a meta-analysis to estimate the effect of high sodium intake using a random effects model. The Newcastle-Ottawa Scale assessment was performed. A random-effects dose-response model was used to estimate the linear and nonlinear dose-response relationships. Subgroup analyses and meta-regression were conducted to explain the observed heterogeneity. We identified 36 reports, which included a total of 616,905 participants, and 20 of these reports were also used for a dose-response meta-analysis. Compared with individuals with low sodium intake, individuals with high sodium intake had a higher adjusted risk of cardiovascular disease (Rate ratio: 1.19, 95% confidence intervals = 1.08-1.30). Our findings suggest that there is a significant linear relationship between dietary sodium intake and cardiovascular disease risk. The risk of cardiovascular disease increased up to 6% for every 1 g increase in dietary sodium intake. A low-sodium diet should be encouraged and education regarding reduced sodium intake should be provided.
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http://dx.doi.org/10.3390/nu12102934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601012PMC
September 2020

Association of Heart Rate Trajectory Patterns with the Risk of Adverse Outcomes for Acute Heart Failure in a Heart Failure Cohort in Taiwan.

Acta Cardiol Sin 2020 Sep;36(5):439-447

Institute of Epidemiology & Preventive Medicine, College of Public School, National Taiwan University.

Background: Heart rate trajectory with multiple heart rate measurements is considered to be a more sensitive predictor of outcomes than single heart rate measurements. The association of heart rate trajectory patterns with acute heart failure outcomes has not been well studied. We examined the association of heart rate trajectory patterns with post-discharge outcomes.

Methods: This prospective cohort study was based on an acute heart failure registry in Taiwan. A total of 1509 patients were enrolled in the Taiwan Society of Cardiology - Heart Failure with Reduced Ejection Fraction Registry from May 2013 to October 2015. The outcomes were post-discharge all-cause mortality and heart failure re-admission.

Results: Two heart trajectory patterns were identified in group-based trajectory analysis. One started with a higher heart rate and had an increasing trend over 6 months then a subsequent decline (high-increasing-decreasing group; n = 352; 23.9%). The other started with a lower heart rate and had a relatively stable pattern (low-stable group; n = 1121; 76.1%). Compared with those in the low-stable group, patients in the high-increasing-decreasing group had a higher risk of events (all-cause mortality: hazard ratio 3.10 and 95% confidence interval 1.24-7.77; heart failure re-admission: hazard ratio 1.13 and 95% confidence interval 0.55-2.32).

Conclusions: Patients with a high-increasing-decreasing heart rate trajectory pattern had a higher risk of all-cause mortality than those with a low-stable pattern.
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http://dx.doi.org/10.6515/ACS.202009_36(5).20200519ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490605PMC
September 2020

Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia.

Biosci Rep 2020 09;40(9)

Institute of Epidemiology and Preventive Medicine, Department of Public Health, College of Public Health, National Taiwan University, Taipei.

Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33-2.15), 1.61 (1.25-1.98), 1.61 (1.01-2.21), and 1.68 (1.19-2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.
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http://dx.doi.org/10.1042/BSR20201885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507599PMC
September 2020

Clinical Outcomes of Complete Left Bundle Branch Block According to Strict or Conventional Definition Criteria in Patients with Normal Left Ventricular Function.

Acta Cardiol Sin 2020 Jul;36(4):335-342

Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital and National Taiwan University College of Medicine.

Background: Complete left bundle branch block (cLBBB) is associated with poor outcomes in patients with heart failure (HF) but appears to have minimal effects on cardiovascular (CV) mortality in relatively healthy adults. New criteria to define strict cLBBB have been proposed.

Objectives: The aim of this study was to stratify the potential risk of cLBBB according to conventional or strict criteria in patients with normal ejection fraction (EF).

Methods: Patients with cLBBB from 2010 to 2013 who underwent baseline echocardiography within 1 year and had a left ventricular ejection fraction (LVEF) > 50% were enrolled. A control group of patients without intraventricular conduction abnormalities matched for age and sex was included. Primary outcomes including CV mortality, HF admission, EF reduction of 40%, and total mortality were compared.

Results: A total of 137 patients with cLBBB were included, of whom 118 had strict cLBBB. The mean age was 72 ± 15 years and 56.2% were men. With a median follow-up of 4.3 years, normal LVEF patients with cLBBB but without a history of atrial fibrillation had a significantly higher risk of CV mortality (p < 0.001), EF reduction to 40% (p < 0.001), and admission for HF (p < 0.001). A similar risk of CV events was noted for the patients with conventional and strict cLBBB.

Conclusions: In patients with normal EF and without a history of atrial fibrillation, the presence of cLBBB led to a greater risk of CV mortality, HF admission and EF reduction to < 40%. Strict cLBBB carries a similar risk of CV events to conventional cLBBB.
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http://dx.doi.org/10.6515/ACS.202007_36(4).20191230ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355119PMC
July 2020

Efficacy of more intensive lipid-lowering therapy on cardiovascular diseases: a systematic review and meta-analysis.

BMC Cardiovasc Disord 2020 07 13;20(1):334. Epub 2020 Jul 13.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, No.17, Xu-Zhou Rd, Taipei City, 10055, Taiwan.

Background: Cardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5-10 per 1000 person-years, according to primary prevention studies. To control hyperlipidemia-a major risk factor of cardiovascular disease-initiation of lipid-lowering therapy with therapeutic lifestyle modification or lipid-lowering agent is recommended. Few systematic reviews and meta-analyses are available on lipid-lowering therapy for the primary prevention of cardiovascular diseases. In addition, the operational definitions of intensive lipid-lowering therapies are heterogeneous. The aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater cardiovascular disease risks in primary prevention settings.

Methods: MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2019 for randomized controlled trials. We used random effects model for overall pooled risk ratio (RR) estimation with cardiovascular events of interest and all-cause mortality rate for the intensive lipid-lowering group using the standard lipid-lowering group as the reference. The Cochrane Risk of Bias Tool was used for quality assessment.

Results: A total of 18 randomized controlled trials were included. The risk reductions in cardiovascular outcomes and all-cause mortality associated with more intensive vs. standard lipid-lowering therapy across all trials were 24 and 10%, respectively (RR 0.76, 95% confidence interval 0.68-0.85; RR 0.90, 95% confidence interval 0.83-0.97); however, the risk reduction varied by baseline LDL-C level in the trial. A greater risk reduction was noted with higher LDL-C level. Intensive lipid-lowering for coronary heart disease protection was more pronounced in the non-diabetic populations than in the diabetic populations.

Conclusions: More intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels than less intensive LDL-C lowering. Intensive lipid-lowering was associated with a significant risk reduction of coronary heart disease and must be considered even in the non-diabetic populations.
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http://dx.doi.org/10.1186/s12872-020-01567-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359015PMC
July 2020

Applying the CHADS-VASc score to predict the risk of future acute coronary syndrome in patients receiving catheter ablation for atrial fibrillation.

Int J Cardiol Heart Vasc 2020 Aug 28;29:100567. Epub 2020 Jun 28.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: It remains unknown whether catheter ablation for atrial fibrillation (AF) reduces future acute coronary syndrome (ACS) risk or whether the CHADS-VASc score has a role in predicting this risk. We aimed to compare very long-term risk of ACS between patients who received catheter ablation to AF or antiarrhythmic medications and controls without AF.

Methods: Propensity scores were calculated for each patient and used to assemble a cohort of 787 patients undergoing AF ablation in 2003-2012. Patients were compared to an equal number of AF patients treated with antiarrhythmic medications and a control group without AF. Patients with previous coronary events were excluded. The primary endpoint was ACS occurrence.

Results: Baseline clinical characteristics were comparable. After a mean 9.1 ± 3.2-year follow-up, the ablation group had lower incidence of new onset ACS than the medication and non-AF control groups (annual incidence: 0.15%. 0.78%, and 0.35%; with 2.67, 4.16, and 10.44 cases/1000 person-years, respectively; P < 0.001). After adjusting for multiple confounders, the ablation group had lower future ACS risk than the medication (hazard ratio [HR]: 0.20, 95% confidence interval [CI]: 0.13-0.30) and control groups (HR: 0.30, 95% CI: 0.20-0.45). The CHADS-VASc score was a strong predictor of ACS (HR: 1.61, 95% CI: 1.47-1.76; AUC: 85.9%, 95% CI: 78.5-93.2%). A baseline CHADS-VASc score ≥ 4 predicted future ACS (positive predictive rate: 14.3%).

Conclusions: This study suggested that catheter ablation for AF may be beneficial to reduce future ACS risk in AF patients, and a high baseline CHADS-VASc score can predict future acute coronary events.
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http://dx.doi.org/10.1016/j.ijcha.2020.100567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330062PMC
August 2020

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Gerontology 2020 1;66(5):447-459. Epub 2020 Jul 1.

Department of Clinical Medicine, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.
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http://dx.doi.org/10.1159/000508498DOI Listing
October 2021
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