Khuan Yew Chow

Retinal Microvascular Changes and Risk of Stroke The Singapore Malay Eye Study

Background and Purpose— To examine the relationship between retinal microvascular measures and incident stroke in an Asian Malay population. Methods— We conducted a prospective, population-based cohort study of Asian Malay persons 40 to 80 years at baseline. Retinal microvascular signs were assessed from baseline retinal photographs including quantitative retinal microvascular parameters (caliber, branching angle, tortuosity, and fractal dimension) and qualitative retinopathy signs. Incident stroke cases were identified during the follow-up period. Cox proportional-hazards regression and incremental usefulness analysis (calibration, discrimination, and reclassification) were performed. Results— A total of 3189 participants were free of prevalent stroke at baseline. During the follow-up (median, 4.41 years), 51 (1.93%) participants had an incident stroke event. In Cox proportional-hazards models adjusting for established stroke predictors (age, sex, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, smoking, glycosylated hemoglobin, and antihypertensive medication), retinopathy (hazard ratio, 1.94; 95% confidence interval, 1.01–3.72) and larger retinal venular caliber (hazard ratio, 3.28; 95% confidence interval, 1.30–8.26, comparing fourth versus first quartiles) were associated with risk of stroke. Compared with the model with only established risk factors, the addition of retinal measures improved the prediction of stroke (C-Statistic 0.826 versus 0.792; P=0.017) and correctly reclassified 5.9% of participants with incident stroke and 3.4% of participants with no incident stroke. Conclusions— Retinal microvascular changes are related to an increased risk of stroke in Asian Malay, consistent with data from white populations. Retinal imaging improves the discrimination and stratification of stroke risk beyond that of established risk factors by a significant but small margin.

Chronic kidney disease, cardiovascular disease and mortality: A prospective cohort study in a multi-ethnic Asian population.

Background Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population. Design Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950). Methods CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries. Results Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05–2.27) and 2.21 (1.67–2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49–5.29) and 2.34 (1.28–4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%). Conclusions In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.

Incidence of Myocardial Infarction, Stroke, and Death in Patients With Age-Related Macular Degeneration Treated With Intravitreal Anti–Vascular Endothelial Growth Factor Therapy

PURPOSE To describe the rates of myocardial infarction (MI), stroke, and mortality in patients who have treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD). DESIGN A retrospective population linkage study. METHOD We identified patients aged 40 years and above who received treatment with intravitreal anti-VEGF injections for AMD from January 1, 2008 to December 31, 2011 at the Singapore National Eye Centre. We used a national record linkage database to identify patients who developed MI, stroke, and all-cause mortality after the first injection, excluding those with previous MI or stroke at baseline from the respective analysis. We compared rates of MI, stroke, and mortality to that of the total Singapore population. RESULTS A total of 1182 individuals had an intravitreal anti-VEGF injection included in this analysis, with the majority receiving bevacizumab (n = 1011). Overall, 19 patients developed MI, 16 developed stroke, and there were 43 mortalities, giving an age-adjusted incidence rate of 350.2 per 100 000 person-years for MI, 299.3 per 100 000 person-years for stroke, and 778.9 per 100 000 person-years for mortality. This is comparable to the weighted incidence rates of the Singapore population (427.1 per 100 000 person-years for MI, 340.4 per 100 000 person-years for stroke, and 921.3 per 100 000 person-years for mortality). CONCLUSION The incidence rate of MI, stroke, and death in this cohort of AMD patients treated with anti-VEGF was low, and was not significantly higher than the age-adjusted incidence rate of these events in the Singapore population.

Effect of childbirth after treatment on long-term survival from breast cancer

This study quantified long‐term absolute and relative mortality risks of survivors of breast cancer with subsequent childbirth.

Retinal microvascular abnormalities and risk of renal failure in Asian populations.

Background Retinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population. Methods A total of 5763 subjects (aged ≥40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis. Retinopathy was graded using the modified Airlie House classification system. Retinal vascular parameters were measured using computer-assisted programs to quantify the retinal vessel widths (arteriolar and venular caliber) and retinal vascular network (fractal dimension). Data on ESRD was obtained by record linkage with the ESRD cases registered by National Registry of Diseases Office, Singapore. Multi-variable adjusted regression analyses were performed to assess the associations of baseline retinal vascular parameters and prevalent and incident ESRD. Results At baseline, 21(0.36%) persons had prevalent ESRD. During a median follow-up of 4.3 years, 33 (0.57%) subjects developed ESRD. In our analyses, retinopathy was associated with prevalent ESRD (multi-variable adjusted odds ratio [OR], 3.21, 95% confidence interval [CI]: 1.28–8.05) and incident ESRD (multi-variable adjusted hazard ratio [HR], 2.51, 95%CI: 1.14–5.54). This association was largely seen in person with diabetes (HR, 2.60, 95%CI: 1.01–6.66) and not present in persons without diabetes (HR, 1.65, 95%CI: 0.14–18.98). Retinal arteriolar caliber, retinal venular caliber and retinal vascular fractal dimension were not associated with ESRD. Conclusion Retinopathy signs in persons with diabetes are related to an increased risk of ESRD; however, other microvascular changes in the retina are not associated with ESRD.

The Low Fall as a Surrogate Marker of Frailty Predicts Long-Term Mortality in Older Trauma Patients.

Background Frailty is associated with adverse outcomes including disability, mortality and risk of falls. Trauma registries capture a broad range of injuries. However, frail patients who fall comprise a large proportion of the injuries occurring in ageing populations and are likely to have different outcomes compared to non-frail injured patients. The effect of frail fallers on mortality is under-explored but potentially significant. Currently, many trauma registries define low falls as less than three metres, a height that is likely to include non-frailty falls. We hypothesized that the low fall from less than 0.5 metres, including same-level falls, is a surrogate marker of frailty and predicts long-term mortality in older trauma patients. Methods Using data from the Singapore National Trauma Registry, 2011–2013, matched till September 2014 to the death registry, we analysed adults aged over 45 admitted via the emergency department in public hospitals sustaining blunt injuries with an injury severity score (ISS) of 9 or more, excluding isolated hip fractures from same-level falls in the over 65. Patients injured by a low fall were compared to patients injured by high fall and other blunt mechanisms. Logistic regression was used to analyze 12-month mortality, controlling for mechanism of injury, ISS, revised trauma score (RTS), co-morbidities, gender, age and age-gender interaction. Different low fall height definitions, adjusting for injury regions, and analyzing the entire adult cohort were used in sensitivity analyses and did not change our findings. Results Of the 8111 adults in our cohort, patients who suffered low falls were more likely to die of causes unrelated to their injuries (p<0.001), compared to other blunt trauma and higher fall heights. They were at higher risk of 12-month mortality (OR 1.75, 95% CI 1.18–2.58, p = 0.005), independent of ISS, RTS, age, gender, age-gender interaction and co-morbidities. Falls that were higher than 0.5m did not show this pattern. Males were at higher risk of mortality after low falls. The effect of age on mortality started at age 55 for males, and age 70 for females, and the difference was attributable to the additional mortality in male low-fallers. Conclusions The low fall mechanism can optimize prediction of long-term mortality after moderate and severe injury, and may be a surrogate marker of frailty, complementing broader-based studies on aging.

Impact of Visual Impairment and Eye diseases on Mortality: the Singapore Malay Eye Study (SiMES).

We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40–80 years between 2004–2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25–1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24–2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25–2.36) and CVD mortality (HR 1.57; 95% CI, 1.05–2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26–7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.

Physical activity and risk of end‐stage kidney disease in the Singapore Chinese Health Study

To explore the relationship between physical activity and risk of end‐stage kidney disease (ESKD).

Smoking and risk of kidney failure in the Singapore Chinese health study.

Background The relationship between smoking and risk of kidney failure, especially in people of Chinese origin, is not clear. We analyzed data from the Singapore Chinese Health Study to investigate whether smoking increases the risk of kidney failure. Methods The Singapore Chinese Health Study is a population-based cohort of 63,257 Chinese adults enrolled between 1993 and 1998. Information on smoking status was collected at baseline. Incidence of kidney failure was identified via record linkage with the nationwide Singapore Renal Registry until 2008. Kidney failure was defined by one of the following: 1) serum creatinine level of more than or equal to 500 µmol/l (5.7 mg/dl), 2) estimated glomerular filtration rate of less than 15 ml/min/1.73 m2, 3) undergoing hemodialysis or peritoneal dialysis, 4) undergone kidney transplantation. Cox proportional hazard regression analysis was performed for the outcome of kidney failure after adjusting for age, education, dialect, herbal medications, body mass index, sex, physician-diagnosed hypertension and diabetes mellitus. Results The mean age of subjects was 55.6 years at baseline, and 44% were men. Overall 30.6% were ever smokers (current or former) at baseline. A total of 674 incident cases of kidney failure occurred during a median follow-up of 13.3 years. Among men, smokers had a significant increase in the adjusted risk of kidney failure [hazard ratio (HR): 1.29; 95% CI: 1.02–1.64] compared to never smokers. There was a strong dose-dependent association between number of years of smoking and kidney failure, (p for trend = 0.011). The risk decreased with prolonged cessation (quitting ≥10 years since baseline). The number of women smokers was too few for conclusive relationship. Limitation Information on baseline kidney function was not available. Conclusions Cigarette smoking is associated with increased risk of kidney failure among Chinese men. The risk appears to be dose- and duration-dependent and modifiable after long duration of cessation.

Gender and ethnic differences in incidence and survival of lymphoid neoplasm subtypes in an Asian population: Secular trends of a population-based cancer registry from 1998 to 2012

Descriptive epidemiology on incidence and survival by lymphoid neoplasm (LN) subtypes using the 2008 World Health Organisation (WHO) classification remained limited in Asia. The aim of this study was to evaluate whether gender and ethnic differences in incidence and survival of LN subtypes existed using the Singapore Cancer Registry (SCR) from 1998 to 2012. We derived age standardised incidence rates (ASIRs) by the direct standardisation method and 5‐year relative survival (RSR) by the Ederer II method and period approach. Five‐year observed survival (OS) was obtained for each ethnicity. Malays had the highest ASIR of total LNs among the three ethnicities for each time period. The largest increase in 5‐year RSR subtypes was follicular lymphoma from 43.8% in 1998–2002 to 82.3% in 2008–2012; followed by chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) from 48.1% in 1998–2002 to 77.9% in 2008–2012. Although males had higher incidence than females in each time period, females had greater 5‐year RSR for follicular lymphoma (89.8% in 2008–2012 for females vs. 76.6% in 2008–2012 for males) and CLL/SLL (78.7% in 2008–2012 for females vs. 76.7% in 2008–2012 for males). All three ethnicities experienced an overall increase in 5‐year OS for mature B‐cell lymphoma, with Indians experiencing the greatest increase (37.1% in 1998–2002 to 61.1% in 2008–2012), followed by Malays (30.8% in 1998–2002 to 48.7% in 2008–2012) and then Chinese (36.4% in 1998–2002 to 51.3% in 2008–2012). Our study demonstrated that improved mature B‐cell lymphoma survival was not only observed in the West, but also in Singapore.