Fei Gao
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gmsgf@nus.edu.sg
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Publication Pitfalls in statistical methods(2013-08) Gao, F.; Machin, D.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREPublication Long-term prognosis and risk heterogeneity of heart failure complicating acute myocardial infarction(2015) De Carvalho, Leonardo Pinto; Gao, Fei; Chen, Qifeng; Sim, Lingling; Koh, Tianhai; Foo, David; Ong, Heanyee; Tong, Khimleng; Tan, Huay Cheem; Yeo, Tiong Cheng; Chow, Khuanyew; Richards, Authur Mark; Peterson, Eric David; Chua, Siang Jin Terence; Chan, Mark Y.; MEDICINEPublication Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)(2012-11-19) Gao, F.; Machin, D.; Chow, K.-Y.; Sim, Y.-F.; Duffy, S.W.; Matchar, D.B.; Goh, C.-H.; Chia, K.-S.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE; SAW SWEE HOCK SCHOOL OF PUBLIC HEALTHBackground: Gail and others developed a model (GAIL) using age-at-menarche, age-at-birth of first live child, number of previous benign breast biopsy examinations, and number of first-degree-relatives with breast cancer as well as baseline age-specific breast cancer risks for predicting the 5-year risk of invasive breast cancer for Caucasian women. However, the validity of the model for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and attempted to improve its performance for Singapore women of Chinese, Malay and Indian origins.Methods: Data from the Singapore Breast Screening Programme (SBSP) are used. Motivated by lower breast cancer incidence in many Asian countries, we utilised race-specific invasive breast cancer and other cause mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor information from a nested case-control study within SBSP, alternative models incorporating fewer then additional risk factors were determined. Their accuracy was assessed by comparing the expected cases (E) with the observed (O) by the ratio (E/O) and 95% confidence interval (CI) and the respective concordance statistics estimated.Results: From 28,883 women, GAIL-SBSP predicted 241.83 cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to 1.14). Except for women who had two or more first-degree-relatives with breast cancer, satisfactory prediction was present in almost all risk categories. This agreement was reflected in Chinese and Malay, but not in Indian women. We also found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age-at-birth of first live child and number of first-degree-relatives performed similarly with associated concordance statistics of 0.5997. Taking account of body mass index and parity did not improve the calibration of S-GAIL-SBSP.Conclusions: GAIL can be refined by using national race-specific invasive breast cancer rates and mortality rates for causes other than breast cancer. A revised model containing only three variables (S-GAIL-SBSP) provides a simpler approach for projecting absolute risk of invasive breast cancer in South-East Asia women. Nevertheless its role in counseling the individual women regarding their risk of breast cancer remains problematical and needs to be validated in independent data. © 2012 Gao et al.; licensee BioMed Central Ltd.Publication Exacerbation of cardiovascular ageing by diabetes mellitus and its associations with acyl-carnitines(IMPACT JOURNALS LLC, 2021-06-15) Gao, Fei; Kovalik, Jean-Paul; Zhao, Xiaodan; Chow, Vivian JM; Chew, Hannah; Teo, Louis LY; Tan, Ru San; Leng, Shuang; Ewe, See Hooi; Tan, Hong Chang; Tan, Tsze Yin; Lee, Lye Siang; Ching, Jianhong; Keng, Bryan MH; Zhong, Liang; Koh, Woon-Puay; Koh, Angela S; Assoc Prof Liang Zhong; DEAN'S OFFICE (MEDICINE); DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLObjective: To demonstrate differences in cardiovascular structure and function between diabetic and nondiabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements. Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination. Results: A total of 933 participants (women 56%, n=521) with a mean age 63±13 years were studied. Old diabetics compared to old non-diabetics had lower myocardial relaxation (0.8±0.2 vs 0.9±0.3, p=0.0039); lower left atrial conduit strain (12±4.3 vs 14±4.1, p=0.045), lower left atrial conduit strain rate (-1.2±0.4 vs -1.3±0.5, p=0.042) and lower ratio of left atrial conduit strain to left atrial booster strain (0.5±0.2 vs 0.7±0.3, p=0.0029). Higher levels of archived short chain acyl-carnitine were associated with present-day impairments in myocardial relaxation (C5:1; OR 1.03, p=0.011), worse left atrial conduit strain function (C5:1; OR 1.03, p=0.037). Increases in hydroxylated acylcarnitines were associated with worse left atrial conduit strain [(C4-OH; OR 1.05, p=0.0017), (C16:2-OH; OR 1.18, p=0.037)]. Current, archived and changes in long chain acyl-carnitines were associated with cardiovascular functions [(C16; OR 1.02, p=0.002), (C20:3; OR 1.01, p=0.014), (C14:3; OR 1.12, p=0.033), (C18:1; OR 1.01, p=0.018), (C18:2; OR 1.01, p=0.028), (C20:4; OR 1.10, p=0.038)] (all p<0.05). Conclusion: Older diabetic adults had significant impairments in left ventricular myocardial relaxation and left atrial strain, compared to older non-diabetic adults. Short chain and long chain, di-carboxyl and hydroxylated acyl-carnitines were associated with these cardiovascular functional differences.Publication Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways(S. Karger AG, 2022-03-22) Koh A.S.; Siau A.; Gao F.; Chioh F.W.J.; Leng S.; Zhao X.; Zhong L.; Tan R.S.; Koh P.L.; Kovalik J.-P.; Lim W.S.; Lee G.S.; Koh W.-P.; Cheung C.; DEAN'S OFFICE (MEDICINE); MEDICINE; DUKE-NUS OFFICE OF ACAD & CLINICAL DEVT; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLIntroduction: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. Methods: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (εs), conduit strain (εe), and booster strain (?a) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. Results: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, εe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with <2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both εe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and εe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of εe from 0.72 to 0.77 (p = 0.015). Conclusion: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes.Publication Platelet inhibition to target reperfusion injury trial: Rationale and study design(WILEY, 2019-01-01) Bulluck, Heerajnarain; Chan, Mervyn HH; Bryant, Jennifer A; Chai, Ping; Chawla, Ashish; Chua, Terrance S; Chung, Yiu-Cho; Fei, Gao; Ho, Hee H; Ho, Andrew FW; Hoe, Andrew J; Imran, Syed S; Lee, Chi-Hang; Lim, Swee H; Liew, Boon W; Yun, Patrick LZ; Hock, Marcus OE; Paradies, Valeria; Roe, Matthew T; Teo, Lynette; Wong, Aaron S; Wong, Evelyn; Wong, Philip E; Watson, Timothy; Chan, Mark Y; Tan, Jack W; Hausenloy, Derek J; Assoc Prof Yan Yee Mark Chan; MEDICINE; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH; DUKE-NUS MEDICAL SCHOOLBackground: In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. Methods: The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120-minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). Results: The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. Summary: The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.Publication Assessment of left ventricular preload by cardiac magnetic resonance imaging predicts exercise capacity in adult operated tetralogy of Fallot: A retrospective study(BioMed Central Ltd., 2014) Yap J.; Le Tan J.; Le T.T.; Gao F.; Zhong L.; Liew R.; Tan S.Y.; Tan R.S.; DUKE-NUS MEDICAL SCHOOLBackground: The optimal timing of pulmonary homograft valve replacement (PVR) is uncertain. Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) are often used to guide the clinical decision for PVR in operated tetralogy of Fallot (TOF) patients with significant pulmonary regurgitation (PR). We aim to study the relationship between exercise capacity and CMR in these patients.Methods: The study is a single-centre retrospective analysis of 36 operated TOF patients [median 21.4 (interquartile range 16.4, 26.4) years post-repair; 30 NYHA I, 6 NYHA II; median age 25.2 (interquartile range 19.5-31.7) years, 29 males] with significant PR on CMR who underwent CPET within 15 [median 2.0 (interquartile range 0.8-7.2)] months from CMR. CPET parameters were compared with 30 age- and sex-matched healthy controls [median age 27.8 (interquartile range 21.0-32.8) years; 24 males].Results: Peak systolic blood pressure (177 versus 192 mmHg, p = 0.007), Mets (7.3 versus 9.9, p < 0.001), peak oxygen consumption (VO2max) (29.2 versus 34.5 ml/kg/min, p < 0.001) and peak oxygen pulse (11.0 versus 13.7 ml/beat, p = 0.003) were significantly lower in TOF group versus control. Univariate analyses showed negative correlation between PR fraction and anaerobic threshold. There was a positive correlation between indexed left (LV) and right (RV) ventricular end-diastolic volumes, as well as indexed LV and effective RV stroke volumes, on CMR and VO2max and Mets achieved on CPET. These remained significant after adjustment for age and sex.Conclusions: TOF subjects have near normal exercise capacity but significantly lower Mets, VO2max and peak oygen pulse achieved compared to controls. Increased PR fraction in TOF subjects was associated with lower anaerobic threshold. Higher indexed effective RV stroke volume, a measure of LV preload, was associated with higher VO2max and Mets achieved, and may potentially be used as a predictor of exercise capacity. © 2014 Yap et al.; licensee BioMed Central Ltd.Publication Mammographic density and its interaction with other breast cancer risk factors in an Asian population(2011-03-01) Wong, C.S.; Lim, G.H.; Gao, F.; Jakes, R.W.; Offman, J.; Chia, K.S.; Duffy, S.W.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE; EPIDEMIOLOGY & PUBLIC HEALTHBackground: Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear. Methods: From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression. Results: Density was a significant risk factor, adjusting for other factors. Density of 76-100% had an odds ratio of 5.54 (95% CI 2.38-12.90) compared with 0-10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02).Conclusions:Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs. © 2011 Cancer Research UK All rights reserved.Publication Quality-of-life-adjusted survival analysis of concurrent chemo radiotherapy for locally advanced (nonmetastatic) nasopharyngeal cancer(2010-10-01) Gao, F.; Wee, J.; Wong, H.B.; MacHin, D.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREPurpose: To assess whether the benefits of adding cisplatin (CDDP) concurrent with radiotherapy, followed by adjuvant CDDP and fluorouracil, justifies the toxicity cost for nasopharyngeal cancer (NPC) using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Methods and Materials: One hundred seven patients treated with radiotherapy (RT) and 111 with concurrent chemotherapy and radiotherapy (CRT) were analyzed. The overall survival was divided into three health states: time on active treatment only, during which any subjective nonhematologic toxic event of grade > = 3 was reported; time without symptoms of disease relapse; or treatment and time following first disease RELapse. The relative advantage of CRT and RT was examined by conducting the analysis cumulatively at restriction times 3, 6, 24, 36, 48 months. Results: At 48 months, the improvement in disease-free survival was 14.4% for CRT, whereas that for overall survival was 18.9%. The differences in Q-TWiST were -0.4, -0.7, 0.1, 1.6, and 3.6 months at 3, 6, 24, 36, and 48 months, respectively, with positive differences favoring CRT. At 24 months, the difference in Q-TWiST began to favor CRT. At 36 months, CRT may be the preferred option from the patient's viewpoint if the time spent in the REL state is valued to bePublication Influence of Ethnicity, Age, and Time on Sex Disparities in Long-Term Cause-Specific Mortality After Acute Myocardial Infarction(WILEY-BLACKWELL, 2016-01-10) Gao, Fei; Lam, Carolyn SP; Yeo, Khung Keong; Machin, David; de Carvalho, Leonardo P; Sim, Ling Ling; Koh, Tian Hai; Foo, David; Ong, Hean Yee; Tong, Khim Leng; Tan, Huay Cheem; Earnest, Arul; Chua, Terrance; Chan, Mark Yan Yee; Assoc Prof Yan Yee Mark Chan; MEDICINE; DUKE-NUS MEDICAL SCHOOLBackground-We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort. Methods and Results-For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22-101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age-adjusted hazard ratio [HR] 1.3, 95% CI 1.2-1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8-1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2-1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9-6.0] versus HR 1.5 [95% CI 0.6-3.6] for Indian women). Compared with same-age Malay men, Malay women aged 22 to 49 years had a 2.5-fold (95% CI 1.6-3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5-2.4) at 30 days to 0.9 (95% CI 0.5-1.6) at 10 years. Conclusion-Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.
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