Asian Cohort Research Articles

Community-level Knowledge, Attitudes, and Practices regarding Cardiovascular Diseases and Modifiable Risk Factors in India.

Assessment of knowledge, attitudes, and practices regarding cardiovascular diseases (CVD) and cardiovascular risk factors (CVRF) is critical to inform CVD prevention strategies, but limited community-level data exist from developing countries. To assess the knowledge, attitudes, and practices regarding CVD and CVRF and acceptability of non-physician health workers and text-message based reminders to guide CVD prevention strategies in India. We conducted a telephone-based survey nested in the on-going Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort in Delhi and Chennai, India between January 2021 to February 2021. We randomly selected people with CVRF, but no established CVD and those with existing CVD from the CARRS cohort (n=502 participants) and assessed their 1) knowledge of CVD symptoms and risk factors, 2) attitude towards non-physician health workers (NPHW) facilitated care and text-messages for healthy lifestyle, and 3) practices regarding monitoring of CVRF. We performed logistic regression analyses to investigate the factors associated with KAP. We interviewed 502 participants (283 with CVRF and 219 with CVD); 45.8% were female, and mean age (SD) was 48.1 (11.2) years. The knowledge of heart attack symptoms, stroke symptoms, and CVRF (>75% correct answers) were: 12.9%, 20.7%, and 17.3%, respectively. Individuals with CVRF had 2.5 times lower knowledge of CVD symptoms compared to those with existing CVD. Acceptability of NPHW-facilitated care and text-messages for healthy lifestyle was 60% and 84%, respectively. The knowledge of CVD symptoms and risk factors is below optimal levels, particularly among individuals at high risk of CVD, unskilled workers, those with lower levels of education and income. Innovative use of NPHW along with mHealth tools could potentially offer solutions to reduce the burden of CVD.

The Prognostic Role of Pre-Treatment Neutrophil-to-Lymphocyte Ratio in an Asian Cohort of Patients with Oropharyngeal Squamous Cell Carcinoma

Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC.

Changes in the estimated glucose disposal rate and incident cardiovascular disease: two large prospective cohorts in Europe and Asia

Background and aimsPrevious study found that estimated glucose disposal rate (eGDR) was significantly associated with cardiovascular disease (CVD). However, little is known about the change in eGDR over time and its association with the development of CVD. The aim of this study was to investigate the association of change in eGDR with CVD risk.MethodsThis study used data of two prospective cohorts: UK Biobank and China Health and Retirement Longitudinal Study (CHARLS) with two measurements of eGDR. Changes in the eGDR were classified using K‑means clustering analysis, and the cumulative eGDR was also calculated. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders.ResultsA total of 11,682 individuals from the UK Biobank, and 4,974 individuals from the CHARLS were included. The median follow-up periods were 9.7 years in the UK Biobank and 3.0 years in the CHARLS. Compared with persistently high level of eGDR (class 1), individuals with low level increasing (class 3) and persistently low level of eGDR (class 4) showed elevated risks of incident CVD in both UK Biobank (HR = 2.79, 95% 2.15–3.62 for class 3; HR = 3.19, 95% 2.50–4.08 for class 4) and CHARLS (HR = 1.66, 95% 1.29–2.13 for class 3; HR = 1.69, 95% 1.34–2.14 for class 4). In addition, lower level of cumulative eGDR were associated with elevated risks of incident CVD. The dose-response curve between cumulative eGDR and CVD risk showed a negative linear relationship.ConclusionDifferent changes in eGDR level are associated with different risks of incident CVD. Dynamic monitoring of eGDR level is of significant importance for the CVD prevention and treatment.

Asthma prescribing trends, inhaler adherence and outcomes: a Real-World Data analysis of a multi-ethnic Asian Asthma population

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1–3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75–1.2: 0.73–0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59–0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61–0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01–1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08–1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84–0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47–1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05–1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities.

Prognostic Implications of MRI-assessed Intratumoral Fat in Hepatocellular Carcinoma: An Asian and European Cohort Study.

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019). MRI scans were independently evaluated by three radiologists at each hospital. Based on Liver Imaging Reporting and Data System (LI-RADS) version 2018, intratumoral fat was defined as "fat in mass more than adjacent liver," and the homogeneous subtype was defined as intratumoral fat "in absence of mosaic and nodule-in-nodule architecture." Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analyses were conducted to identify factors associated with RFS and OS. Results A total of 933 patients were included in the Asian (n = 736; median age, 53 years [IQR, 45-62 years]; 626 male) and European (n = 207; median age, 64 years [IQR, 55-70 years]; 161 male) cohorts. MRI-assessed intratumoral fat was detected in 30% (215 of 726) and 31% (64 of 207) of patients in the Asian and European cohorts, respectively (P = .72). In both cohorts, the steatohepatitic subtype, nonperipheral washout, enhancing capsule, and mosaic architecture were more frequent in tumors with intratumoral fat (P value range, <.001 to .04). Intratumoral fat in general was not associated with RFS or OS in either cohort (P value range, .48-.97). However, in the Asian cohort, homogeneous intratumoral fat was associated with longer RFS (hazard ratio [HR], 0.60; P = .009) and OS (HR, 0.33; P = .008) in multivariable Cox regression analyses. Conclusion MRI-assessed intratumoral fat was more frequent in steatohepatitic HCCs and associated with nonperipheral washout, enhancing capsule, and mosaic architecture. Although intratumoral fat was generally nonprognostic, homogeneous intratumoral fat was associated with longer RFS and OS in the Asian cohort. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Comparative analysis of INTERGROWTH-21st and Fenton growth charts for birthweight classification in a multiethnic Asian cohort: a cross-sectional study.

The objective of this study is to evaluate the impact of using International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) (IG-21) growth standards compared with Fenton growth charts on birthweight classification in a multiethnic newborn cohort in Singapore. Cross-sectional study. KK Women's and Children's Hospital, Singapore. Study population included 2541 babies born between 16 December 2019 and 16 March 2020. None. Birthweight classifications of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) were assessed using IG-21 and Fenton growth charts. The level of agreement between the two charts was measured using Cohen's kappa coefficient (K). Of 2541 neonates, 171 (6.7%) had discordant birthweight classifications. The kappa coefficient indicated moderate overall agreement (K=0.79) between the charts, with decreasing agreement from preterm (K=0.88) to full-term categories (K=0.71). The largest discordance was observed in 98 (60.5%) neonates classified as LGA by IG-21 but AGA by Fenton. In comparison, 60 (2.9%) neonates classified as AGA by IG-21 were SGA by Fenton, while 13 (4.6%) were SGA by IG-21 but AGA by Fenton. The study found discrepancies in birthweight classification between IG-21 and Fenton growth charts, with Fenton charts overclassifying SGA and underclassifying LGA in our study population. These findings suggest the potential need to integrate IG-21 growth standards into local practice to improve accuracy in neonatal growth assessment. Further research is necessary to evaluate the clinical implications of these discordant classifications on neonatal outcomes.

Using interpretable deep learning radiomics model to diagnose and predict progression of early AD disease spectrum: a preliminary [18F]FDG PET study.

In this study, we propose an interpretable deep learning radiomics (IDLR) model based on [18F]FDG PET images to diagnose the clinical spectrum of Alzheimer's disease (AD) and predict the progression from mild cognitive impairment (MCI) to AD. This multicentre study included 1962 subjects from two ethnically diverse, independent cohorts (a Caucasian cohort from ADNI and an Asian cohort merged from two hospitals in China). The IDLR model involved feature extraction, feature selection, and classification/prediction. We evaluated the IDLR model's ability to distinguish between subjects with different cognitive statuses and MCI trajectories (sMCI and pMCI) and compared results with radiomic and deep learning (DL) models. A Cox model tested the IDLR signature's predictive capability for MCI to AD progression. Correlation analyses identified critical IDLR features and verified their clinical diagnostic value. The IDLR model achieved the best classification results for subjects with different cognitive statuses as well as in those with MCI with distinct trajectories, with an accuracy of 76.51% [72.88%, 79.60%], (95% confidence interval, CI) while those of radiomic and DL models were 69.13% [66.28%, 73.12%] and 73.89% [68.99%, 77.89%], respectively. According to the Cox model, the hazard ratio (HR) of the IDLR model was 1.465 (95% CI: 1.236-1.737, p < 0.001). Moreover, three crucial IDLR features were significantly different across cognitive stages and were significantly correlated with cognitive scale scores (p < 0.01). Preliminary results demonstrated that the IDLR model based on [18F]FDG PET images enhanced accuracy in diagnosing the clinical spectrum of AD. Question The study addresses the lack of interpretability in existing DL classification models for diagnosing the AD spectrum. Findings The proposed interpretable DL radiomics model, using radiomics-supervised DL features, enhances interpretability from traditional DL models and improves classification accuracy. Clinical relevance The IDLR model interprets DL features through radiomics supervision, potentially advancing the application of DL in clinical classification tasks.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition

Abstract Background The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to &amp;gt; 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from &amp;gt; 3 wood units (WU) to &amp;gt; 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia. Purpose In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort. Methods A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models. Results Based on the new cutoffs (mPAP &amp;gt; 20mmHg, PVR &amp;gt; 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [&amp;lt;25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [&amp;lt;20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR &amp;gt; 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1). Conclusion The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1

Stroke-Heart syndrome: a population-based cohort study and cluster analysis

Abstract Background The onset of acute cardiovascular complications following a stroke, also known as "Stroke-Heart Syndrome", can occur in up to 20% of patients following a stroke. The syndrome remains under-investigated and limited data exists related to the occurrence and impact of the Stroke-Heart Syndrome in an Asian population. Objectives We aimed to investigate the potential impact of the Stroke-Heart Syndrome and its associations in a retrospective population based-cohort study. Methods The analysis included patients with new-onset ischaemic stroke (IS) June 2006 and May 2022 with 5 years’ follow-up. Patients who developed acute cardiovascular complications within 28 days of their index stroke were compared to patients who did not. The association between acute cardiovascular complications and longer term outcomes were evaluated using multivariate Fine-Grey analyses to adjust for competing risk of mortality, and a Cox regression model for all-cause mortality. Inverse probability of treatment weighting was applied prior to analysis. Furthermore, a hierarchical cluster analysis was performed in the cohort of stroke patients with "Stroke-Heart Syndrome", to further evaluate associations between the identified clusters and (i) longer term outcomes, as well as (ii) the development of acute cardiovascular complications. Results A total of 141,118 patients (median age 72.4 (IQR 62.6 to80.8) years; 45.4% female) were included in the analysis, 6,457 of who developed acute cardiovascular complications, and 134,661 of whom did not. At 5 years follow-up, acute cardiovascular complications were associated with a higher risk of developing recurrent ischaemic stroke (Sub-distribution Hazard Ratio [SHR]: 1.20, 95% Confidence Interval [CI]: 0. 1.12-1.28, p= &amp;lt;0.001), haemorrhagic stroke (SHR: 1.15, 95%CI: 1.03-1.28, p=0.014), myocardial infarction (SHR: 1.53, 95%CI: 1.39-1.69, p=&amp;lt;0.001), and cardiovascular death (SHR: 1.57, 95%CI: 1.45-1.71, p=&amp;lt;0.001) as well as all-cause mortality (HR: 1.07, 95%CI: 1.07-1.07, p=&amp;lt;0.001). A total of 4 clusters were identified in the cluster analysis. Compared to Cluster 3, the other Clusters were associated with increased 5-year risk of myocardial infarction, cardiovascular death and all-cause mortality (p=&amp;lt;0.001). In this cohort, compared to Cluster 2, the other clusters had an increased risk of developing acute cardiovascular complications, in particular acute ischaemic heart disease and acute heart failure (p=&amp;lt;0.001). Cluster 3 tended to be younger with fewer comorbidities and prescribed medications. Over 90% of the patients in Cluster 2 were aged over 75 (with 43% aged 85 years or over). Conclusion Stroke-Heart Syndrome was associated with long-term adverse cardiovascular events in this Asian cohort of ischaemic stroke patients.

Cardiac magnetic resonance (CMR) height-based allometric scaling in Southeast Asians; implications in the diagnosis and prognosis of left ventricular hypertrophy (LVH): the REMODEL study

Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes (1). Although normalizing LV mass (LVM) to height exponents has been shown to reduce variability from body size, specific recommendations for height exponents are lacking due to the scarcity of normal cohorts to define appropriate height exponents (2). Cardiac magnetic resonance (CMR) is increasingly used in assessing LVM, and the existing body of research is based primarily on the MESA cohort (3). While the MESA cohort is ethnically diverse, the intrinsic effects of ethnicity may not fully be discerned if certain ethnic groups are under-represented. Purpose We aimed to demonstrate the diagnostic and prognostic implications of establishing height exponents specific to sex in a Southeast Asian cohort. Methods Non-overweight/obese Southeast Asian healthy volunteers (n=416) were used to establish appropriate height exponents and normal reference ranges of LVM. The impact of these height exponents was examined in a separate cohort of Southeast Asians with hypertension (n=878). All individuals underwent standardized cardiovascular magnetic resonance imaging (CMR). Primary outcome was a composite of acute coronary syndrome, heart failure hospitalization, stroke, and cardiovascular mortality. Cox regression analysis of various LVH measures were adjusted for 24-hour systolic blood pressure, diabetes, and hyperlipidemia. Results The height exponents for healthy females and males were 1.57 and 2.33, respectively. In patients with hypertension, sex-specific height exponents significantly increased the detection of LVH compared with body surface area (BSA) indexing (47% [n=409/878] versus 27% [n= 236/878], p&amp;lt;0.001). Most individuals re-classified to LVH with sex-specific height exponents were overweight (33.1%, n=58/175) or obese (64.6%, n=113/175). There were 37 primary events over 60 [37-73] months of follow-up. Regardless of indexing method, LVH was independently associated with increased adverse events (sex-specific height exponent hazard ratio (HR): 2.8 [1.25-6.29], P=0.013). The prediction ability of LVH diagnosis by sex-specific height exponents was similar to BSA indexing (HR: 5.43 [2.49-11.8], P&amp;lt;0.001). Conclusions Reference ranges specific to the ethnicity, sex and imaging modality are necessary to establish appropriate height exponents. Although utilizing sex-specific height exponents to index LVM resulted in significantly more LVH reclassification when compared with BSA indexing, this did not translate to a notable improvement in event prediction. Further research into alternative methods of LVM indexing is warranted.Abstract SummaryPredictive Ability of LVH Measures

Adult-Onset EIF2B-Pathies: A Clinical, Imaging and Genetic Profiling with Literature Review.

Vanishing white matter syndrome is one of the leukoencephalopathies caused by recessive mutations in gene EIF2B1-5. Adult-onset EIF2B-pathies (clinical onset after age 16 years) have been reported to be less common. Description of the clinical, imaging and genetic profile of adult-onset EIF2B-pathies and comparison of Indian cohort with Asian and European cohorts. Report of two cases of adult-onset EIF2B-pathies and a comprehensive review of genetically confirmed adult-onset EIF2B-pathies since 2001 from Indian, Asian and European cohorts. Two patients were females, with median age at presentation of 25.5 years (24-27 years) and onset at 19 years (18-20 years). The median duration of symptoms was 6.5 years (6-7 years). Both had cerebellar ataxia, spasticity, cognitive impairment and bladder involvement. Brain magnetic resonance imaging (MRI) showed leukoencephalopathy with rarefaction in both patients and corpus callosum involvement in one patient. Genetics showed homozygous missense variant in the EIF2B3 gene in both patients. The Indian cohort of seven patients had similar clinical and radiological features and common variants in EIF2B3 (n = 4). The Asian cohort had 24 cases, and the European cohort had 61 cases with similar clinical features, radiological features and common variants in EIF2B5. Adult-onset EIF2B-pathies have a distinct clinical profile of female predominance with cerebellar ataxia, spasticity and cognitive decline as the commonest triad of clinical manifestations and leukoencephalopathy with rarefaction on brain MRI. Variants in EIF2B5 were common in the Asian and European cohorts and EIF2B3 in the Indian cohort.

The development and progression of albuminuria in South Asians with type 2 diabetes compared with Western Europeans. Results from the HinDu the Hague diabetes study.

Although South Asians have an increased risk to develop diabetes, data on the difference in development and progression of diabetic nephropathy between ethnic groups are not consistent. The aim of this study was to evaluate possible differences in the development and progression of albuminuria in South Asians and Western Europeans (WE) with type 2 diabetes in a large closed cohort of South Asians with type 2 diabetes. Data on 1269 South Asians and 2272 Dutch adults with type 2 diabetes who were treated in our diabetes clinic in 2006 or referred thereafter were extracted from electronic medical records. Microalbuminuria and macroalbuminuria were defined separately for men and women based on albumin/creatinine ratios in early morning urine samples. We defined 3 outcomes: (1) no albuminuria, (2) persistent microalbuminuria and (3) macroalbuminuria at the end of follow-up. Cox proportional hazard models were used to discriminate differences in time from diabetes diagnosis until development and progression of albuminuria between the two ethnic groups, adjusted for retinopathy, hypertension, smoking and age at diabetes diagnosis. South Asians have a higher adjusted risk for developing microalbuminuria: HR 1.4, (95% CI 1.2, 1.6) and macroalbuminuria: HR: 1.2 (1.0, 1.4) compared to Western Europeans. However, mean time to progress from micro- to macroalbuminuria was not different between the ethnic groups (3.9 ± 4.0 yrs vs. 3.4 ± 3.9 yrs respectively). South Asians have a higher adjusted risk to develop micro- and macroalbuminuria compared with Western Europeans. When microalbuminuria is present, time to progression from micro- to macroalbuminuria is not different between the two groups.

Predictive factors for interstitial lung disease progression in a Singapore systemic sclerosis cohort: a multicentre study.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is heterogeneous with varied progression rate. This study aimed to identify the baseline clinical characteristics associated with ILD progression within 1, 3 and 5 years of the diagnosis of ILD. This was a prospective, multicentre study - Systematic Sclerosis Cohort Singapore - conducted from January 2008 to February 2021, which included SSc patients with ILD diagnosed by high-resolution computed tomography. Progression of ILD was defined by forced vital capacity (FVC) decline ≥10% predicted or FVC decline 5%-9% predicted, with diffusing lung capacity of carbon monoxide decline ≥15% from the time of ILD diagnosis. Multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, were performed to determine independent risk factors of ILD progression. Of 124 SSc patients with ILD, 47.6% had limited cutaneous SSc, 33.9% had diffuse SSc and 18.5% had SSc-overlap. Progression of ILD was seen in 6%, 15% and 23% of patients within 1, 3 and 5 years, respectively. After adjusting for malignancy and treatment, anti-La was associated with ILD progression within 1 year (odds ratio [OR] 6.94, 95% confidence interval [CI]: 1.14-42.2; P = 0.04) and 3 years (OR 5.98, 95% CI: 1.31-27.4; P = 0.02), and anti-Scl-70 was associated with ILD progression within 5 years (OR 2.54, 95% CI: 1.05-6.12; P = 0.04). Analysing time to ILD progression as an outcome, anti-La was significantly associated with higher risk of ILD progression (hazard ratio 3.47, 95% CI: 1.18-10.2; P = 0.02). Time to ILD progression was 1.4 years in patients with anti-La versus 6.9 years in patients without anti-La (P = 0.02), and 4.7 years in patients with anti-Scl-70 versus 8.9 years in patients without anti-Scl-70 (P = 0.12). In this Asian cohort of SSc patients, autoantibodies may help to predict ILD progression rates.

Multi-Omics Mendelian Randomization Study Investigating the Impact of PCSK9 and HMGCR Inhibition on Type 2 Diabetes Across Five Populations.

The prevalence of type 2 diabetes (T2D) varies among populations of different race/ethnicity. The influence of genetically-proxied lipoprotein cholesterol (LDL-C) lowering through proprotein convertase subtilisin/kexin 9 (PCSK9) and HMG-CoA Reductase (HMGCR) on T2D in non-European populations is not well established.A drug-target Mendelian randomization (MR) approach was used to assess the effects of PCSK9 and HMGCR inhibition on T2D risk and glycemic traits in five populations: East Asian (EAS), South Asian (SAS), Hispanic (HISP), African (AFR), and European (EUR). Our study did not find relationships between genetically-proxied PCSK9 inhibition and T2D risk in EAS (odds ratio [OR]=1.02, [0.95-1.10]), SAS (OR=1.05, [0.97-1.14]), HISP (OR=1.03, [0.94-1.12]), or EUR (OR=1.04, [0.98-1.11]). However, in AFR, primary analyses suggested an increased risk of T2D due to PCSK9 inhibition (OR=1.53, [1.058-2.22], P-value=0.024), although this was not supported in sensitivity analyses. Genetically-proxied HMGCR inhibition was associated with an increased risk of T2D in SAS (OR=1.44, [1.30-1.61], P-value=9.8×10-12), EAS (OR=1.36, [1.22-1.51], P-value=4.2×10-10), and EUR (OR=1.52, [1.21-1.90], P-value=3.3×10-4). These results were consistent across various sensitivity analyses, including colocalization, indicating a robust finding. The findings indicate a neutral impact of long-term PCSK9 inhibition on T2D and glycemic markers in most non-European populations, with a potential increased risk in AFR cohorts. By contrast, HMGCR inhibition increased the risk of T2D in South Asian, East Asian, and European cohorts, underscoring the need to consider diversity in genetic research on metabolic diseases.

Systematic review and meta-analysis of the association between ABCA7 common variants and Alzheimer's disease in non-Hispanic White and Asian cohorts.

The relationship between the ABCA7 gene and Alzheimer's disease (AD) has been widely studied across various populations. However, the results have been inconsistent. This meta-analysis aimed to evaluate the association of ABCA7 polymorphisms with AD risk, including specific subtypes such as late-onset Alzheimer's disease (LOAD). Relevant studies were identified through comprehensive database searches, and the quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). Allele and genotype frequencies were extracted from the included studies. The pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models. Multiple testing corrections were conducted using the false discovery rate (FDR) method. The Cochran Q statistic and I2 metric were used to evaluate heterogeneity between studies, while Egger's test and funnel plots were employed to assess publication bias. A total of 36 studies, covering 21 polymorphisms and involving 31,809 AD cases and 44,994 controls, were included in this meta-analysis. NOS scores ranged from 7 to 9, indicating high-quality studies. A total of 11 SNPs (rs3764650, rs3752246, rs4147929, rs3752232, rs3752243, rs3764645, rs4147934, rs200538373, rs4147914, rs4147915, and rs115550680) in ABCA7 were significantly associated with AD risk. Among these SNPs, two (rs3764650 and rs3752246) were also found to be related to the late-onset AD (LOAD) subtype. In addition, two SNPs (rs4147929 and rs4147934) were associated with the susceptibility to AD only in non-Hispanic White populations. A total of 10 SNPs (rs3764647, rs3752229, rs3752237, rs4147932, rs113809142, rs3745842, rs3752239, rs4147918, rs74176364, and rs117187003) showed no significant relationship with AD risk. Sensitivity analyses confirmed the reliability of the original results, and heterogeneity was largely attributed to deviations from Hardy-Weinberg equilibrium, ethnicity, and variations between individual studies. The available evidence suggests that specific ABCA7 SNPs may be associated with AD risk. Future studies with larger sample sizes will be necessary to confirm these results. https://www.crd.york.ac.uk/prospero/, identifier: CRD42024540539.

Genetic architecture of routinely acquired blood tests in a British South Asian cohort

Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

Cerebral venous sinus thrombosis - Current updates in the Asian context.

Background Cerebral venous sinus thrombosis (CVT) is a life-threatening cause of stroke in Asian countries. South Asia, comprising of India, Pakistan and Bangladesh and contributed to 40% of strokes in women. Major CVT registries are from the western nations, which differs from the Asian countries with respect to epidemiology, gender biases and risk factors. This review focusses on the various aspects of relevance in evaluation and management of patients with CVT in the Asian context. Summary The incidence of CVT is higher in Asia than in Western nations. Young age, female gender, especially in pregnancy and puerperal period, and dehydration appear to be the critical risk factors. Tropical infections like malaria, scrub typhus, and flaviviral encephalitis predispose to CVT. There is a higher prevalence of inherited thrombophilia in the Asian cohorts, contributing to prothrombotic states. Anticoagulation and supportive management offer excellent outcomes. Newer anticoagulants are safe and efficacious. In medically refractory cases, endovascular treatment offers modest benefits. Decompressive hemicraniectomy, when done early, offers mortality benefits in patients with large hemorrhagic venous infarctions. Key messages CVT is an important cause of stroke with high-burden in South Asian countries. Establishment of robust registries is the need of the hour; to study the natural history, course and outcomes and to develop management algorithms tailored to the available resources.

Comparative analysis of classic and delayed Ménière's disease: clinical characteristics and endolymphatic hydrops manifestations in an Asian cohort.

To investigate the clinical characteristics and endolymphatic hydrops (ELH) Manifestations in patients with delayed Ménière's disease (DMD) compared to classic Ménière's disease (CMD). A prospective cohort study was conducted involving 523 patients diagnosed with MD. Clinical data, inner ear function, and ELH characteristics were analyzed and compared between CMD and DMD groups. Assessments included audiometry, VEMP, and MRI. DMD prevalence was 6.1%. Bilateral MD was significantly more common in DMD (34.4% vs. 14.5%, P = 0.003). DMD patients had more severe hearing loss in the first involved ear and more deteriorated VEMP in the contralateral ear (P < 0.05). ELH was present in 100% of affected ears, with a higher contralateral ELH proportion in DMD (34.4% vs. 15.0%, P = 0.005). DMD patients exhibit a higher prevalence of bilateral MD, more severe hearing loss, and greater contralateral ELH compared to CMD patients. Both subtypes share similar ELH characteristics, suggesting common underlying mechanisms.

Robust Predictive Performance of the SALT-M Score for Clinical Outcomes in Asian Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade. The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018). SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M.