Sarcomeric gene variants among Indians with hypertrophic cardiomyopathy: A scoping review.

Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease that frequently causes sudden cardiac death (SCD) among young adults. Several pathogenic mutations in genes encoding the cardiac sarcomere have been identified as diagnostic factors for HCM and proposed as prognostic markers for SCD. The objective of this review was to determine the scope of available literature on the variants encoding sarcomere proteins associated with SCD reported among Indian patients with HCM. The eligibility criteria for the scoping review included full text articles that reported the results of genetic screening for sarcomeric gene mutations in HCM patients of Indian south Asian ancestry. We systematically reviewed studies from the databases of Medline, Scopus, Web of Science core collection and Google Scholar. The electronic search strategy included a combination of generic terms related to genetics, disease and population. The protocol of the study was registered with Open Science Framework (https://osf.io/53gde/). A total of 19 articles were identified that reported pathogenic or likely pathogenic (P/LP) variants within MYH7, MYBPC3, TNNT2, TNNI3 and TPM1 genes, that included 16 singletons, one de novo and one digenic mutation (MYH7/ TPM1) associated with SCD among Indian patients. Evidence from functional studies and familial segregation implied a plausible mechanistic role of these P/LP variants in HCM pathology. This scoping review has compiled all the P/LP variants reported to-date among Indian patients and summarized their association with SCD. Single homozygous, de novo and digenic mutations were observed to be associated with severe phenotypes compared to single heterozygous mutations. The abstracted genetic information was updated with reference sequence ID (rsIDs) and compiled into freely accessible HCMvar database, available at https://hcmvar.heartfailure.org.in/. This can be used as a population specific genetic database for reference by clinicians and researchers involved in the identification of diagnostic and prognostic markers for HCM.

Charting a roadmap for heart failure research in India: Insights from a qualitative survey.

Background & objectives: Heart failure (HF) is emerging as a major health problem in India. The profile of HF in India is divergent from elsewhere in the world. While cardiologists must equip themselves with the requisite clinical management tools, scientists and health policymakers would need epidemiological data on HF and information on the resources required to meet the challenges ahead. The aim of this study was to identify the lacunae and to suggest recommendations to improve HF research. Methods: We surveyed a multidisciplinary group of HF experts using a two stage process. An email-based survey was conducted using a structured questionnaire, followed by an online discussion. The experts prioritized the major challenges in convergence research in India and inter-rater agreement values were calculated. In addition, they enlisted potential research gaps and barriers in the domains of epidemiology, diagnostics, management and technology and suggested recommendations to overcome those barriers. Results: The experts identified a paucity of data on HF burden, lack of state-of-the-art diagnostic facilities and trained personnel, overt dependence on imported devices/equipment/reagents, lack of interaction/awareness/information among stakeholders and lack of biobanks, as major barriers in HF research. Three fourths of the experts agreed that lack of interaction among stakeholders was the major challenge with the highest inter-rater agreement in both stages (19 out of 25 and 11 out of 17, respectively). The experts recommended the creation of multidisciplinary taskforces dedicated to population sciences, data sciences, technology development and patient management with short-, intermediate- and long-term strategies. Interpretation & conclusions: The study generated a wish list for advances in HF research and management, and proposed recommendations for facilitating convergence research as a way forward to reduce the burden of HF in India.

Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR): design and methodology.

BACKGROUND: Cardiac disease in pregnancy is a major contributor to maternal mortality in high, middle and low-income countries. Availability of data on outcomes of pregnancy in women with heart disease is important for planning resources to reduce maternal mortality. Prospective data on outcomes and risk predictors of mortality in pregnant women with heart disease (PWWHD) from low- and middle-income countries are scarce. METHODS: The Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR) is a prospective, multicentric and multidisciplinary registry of PWWHD from 29 participating sites including both public and private sectors, across the state of Tamil Nadu in India. The TNPHDR is aimed to provide data on incidence of maternal and fetal outcomes, adverse outcome predictors, applicability of the modified World Health Organization (mWHO) classification of maternal cardiovascular risk and the International risk scoring systems (ZAHARA and CARPREG I & II) in Indian population and identify possible gaps in the existing management of PWWHD. Pregnancy and heart teams will be formed in all participating sites. Baseline demographic, clinical, laboratory and imaging parameters, data on counselling received, antenatal triage and management, peripartum management and postpartum care will be collected from 2500 eligible participants as part of the TNPHDR. Participants will be followed up at one, three and six-months after delivery/termination of pregnancy to document study outcomes. Predictors of maternal and foetal outcome will be identified. DISCUSSION: The TNPHDR will be the first representative registry from low- and middle-income countries aimed at providing crucial information on pregnancy outcomes and risk predictors in PWWHD. The results of TNPHDR could help to formulate steps for improved care and to generate a customised and practical guideline for managing pregnancy in women with heart disease in limited resource settings. TRIAL REGISTRATION: The TNPHDR is registered under Clinical Trials Registry-India ( CTRI/2020/01/022736 ).

Enduring language deficits in children of women with epilepsy and the potential role of intrauterine exposure to antiepileptic drugs.

OBJECTIVE: Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9-13 years in comparison with their peers, and its relationship with intrauterine AED exposure. METHODS: We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records. RESULTS: The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% confidence interval [CI] = -8.8 to -0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = -13.8 to -0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (-14.7, 95% CI = -23.1 to -6.4, P = .001) as compared to carbamazepine. SIGNIFICANCE: Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

The association between blood pressure and long-term outcomes of patients with ischaemic cardiomyopathy with and without surgical revascularization: an analysis of the STICH trial.

Aims: Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy. Methods and results: The influence of BP during a median follow-up of 9.8 years was studied in a total of 1212 patients with ejection fraction ≤35% and coronary disease amenable to coronary artery bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED) in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark analyses were performed starting at 1, 2, 3, 4, and 5 years after randomization, in which previous systolic BP values were averaged and related to subsequent mortality through the end of follow-up with a median of 9.8 years. Neither a previous history of HTN nor baseline BP had any significant influence on long-term mortality outcomes, nor did they have a significant interaction with MED or CABG treatment. The landmark analyses showed a progressive U-shaped relationship that became strongest at 5 years (χ2 and P-values: 7.08, P = 0.069; 8.72, P = 0.033; 9.86; P = 0.020; 8.31, P = 0.040; 14.52, P = 0.002; at 1, 2, 3, 4, and 5-year landmark analyses, respectively). The relationship between diastolic BP (DBP) and outcomes was similar. The most favourable outcomes were observed in the SBP range 120-130, and DBP 75-85 mmHg, whereas lower and higher BP were associated with worse outcomes. There were no differences in BP-lowering medications between groups. Conclusion: A strong U-shaped relationship between BP and mortality outcomes was evident in ischaemic HF patients. The results imply that the optimal SBP might be in the range 120-130 mmHg after intervention, and possibly be subject to pharmacologic action regarding high BP. Further, low BP was a marker of poor outcomes that might require other interactions and treatment strategies. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

In-Hospital and Three-Year Outcomes of Heart Failure Patients in South India: The Trivandrum Heart Failure Registry.

BACKGROUND: Long-term data on outcomes of participants hospitalized with heart failure (HF) from low- and middle-income countries are limited. METHODS AND RESULTS: In the Trivandrum Heart Failure Registry (THFR) in 2013, 1205 participants from 18 hospitals in Trivandrum, India, were enrolled. Data were collected on demographics, clinical presentation, treatment, and outcomes. We performed survival analyses, compared groups and evaluated the association between heart failure (HF) type and mortality, adjusting for covariates that predicted mortality in a global HF risk score. The mean (standard deviation) age of participants was 61.2 (13.7) years. Ischemic heart disease was the most common cause (72%). The in-hospital mortality rate was higher for participants with HF with reduced ejection fraction (HFrEF; 9.7%) compared with those with HF with preserved ejection fraction (HFpEF; 4.8%; P = .003). After 3 years, 540 (44.8%) participants had died. The all-cause mortality rate was lower for participants with HFpEF (40.8%) compared with HFrEF (46.2%; P = .049). In multivariable models, older age (hazard ratio [HR] 1.24 per decade, 95% confidence interval [CI] 1.15-1.33), New York Heart Association functional class IV symptoms (HR 2.80, 95% CI 1.43-5.48), and higher serum creatinine (HR 1.12 per mg/dL, 95% CI 1.04-1.22) were associated with all-cause mortality. CONCLUSIONS: Participants with HF in the THFR have high 3-year all-cause mortality. Targeted hospital-based quality improvement initiatives are needed to improve survival during and after hospitalization for HF.

Cardiovascular Diseases in India: Current Epidemiology and Future Directions.

Cardiovascular diseases (CVDs) have now become the leading cause of mortality in India. A quarter of all mortality is attributable to CVD. Ischemic heart disease and stroke are the predominant causes and are responsible for >80% of CVD deaths. The Global Burden of Disease study estimate of age-standardized CVD death rate of 272 per 100 000 population in India is higher than the global average of 235 per 100 000 population. Some aspects of the CVD epidemic in India are particular causes of concern, including its accelerated buildup, the early age of disease onset in the population, and the high case fatality rate. In India, the epidemiological transition from predominantly infectious disease conditions to noncommunicable diseases has occurred over a rather brief period of time. Premature mortality in terms of years of life lost because of CVD in India increased by 59%, from 23.2 million (1990) to 37 million (2010). Despite wide heterogeneity in the prevalence of cardiovascular risk factors across different regions, CVD has emerged as the leading cause of death in all parts of India, including poorer states and rural areas. The progression of the epidemic is characterized by the reversal of socioeconomic gradients; tobacco use and low fruit and vegetable intake have become more prevalent among those from lower socioeconomic backgrounds. In addition, individuals from lower socioeconomic backgrounds frequently do not receive optimal therapy, leading to poorer outcomes. Countering the epidemic requires the development of strategies such as the formulation and effective implementation of evidence-based policy, reinforcement of health systems, and emphasis on prevention, early detection, and treatment with the use of both conventional and innovative techniques. Several ongoing community-based studies are testing these strategies.

Chronic disease concordance within Indian households: A cross-sectional study.

BACKGROUND: The household is a potentially important but understudied unit of analysis and intervention in chronic disease research. We sought to estimate the association between living with someone with a chronic condition and one's own chronic condition status. METHODS AND FINDINGS: We conducted a cross-sectional analysis of population-based household- and individual-level data collected in 4 socioculturally and geographically diverse settings across rural and urban India in 2013 and 2014. Of 10,703 adults ages 18 years and older with coresiding household members surveyed, data from 7,522 adults (mean age 39 years) in 2,574 households with complete covariate information were analyzed. The main outcome measures were diabetes (fasting plasma glucose ≥ 126 mg/dL or taking medication), common mental disorder (General Health Questionnaire score ≥ 12), hypertension (blood pressure ≥ 140/90 mmHg or taking medication), obesity (body mass index ≥ 30 kg/m2), and high cholesterol (total blood cholesterol ≥ 240 mg/dL or taking medication). Logistic regression with generalized estimating equations was used to model associations with adjustment for a participant's age, sex, education, marital status, religion, and study site. Inverse probability weighting was applied to account for missing data. We found that 44% of adults had 1 or more of the chronic conditions examined. Irrespective of familial relationship, adults who resided with another adult with any chronic condition had 29% higher adjusted relative odds of having 1 or more chronic conditions themselves (adjusted odds ratio [aOR] = 1.29; 95% confidence interval [95% CI] 1.10-1.50). We also observed positive statistically significant associations of diabetes, common mental disorder, and hypertension with any chronic condition (aORs ranging from 1.19 to 1.61) in the analysis of all coresiding household members. Associations, however, were stronger for concordance of certain chronic conditions among coresiding household members. Specifically, we observed positive statistically significant associations between living with another adult with diabetes (aOR = 1.60; 95% CI 1.23-2.07), common mental disorder (aOR = 2.69; 95% CI 2.12-3.42), or obesity (aOR = 1.82; 95% CI 1.33-2.50) and having the same condition. Among separate analyses of dyads of parents and their adult children and dyads of spouses, the concordance between the chronic disease status was striking. The associations between common mental disorder, hypertension, obesity, and high cholesterol in parents and those same conditions in their adult children were aOR = 2.20 (95% CI 1.28-3.77), 1.58 (95% CI 1.15-2.16), 4.99 (95% CI 2.71-9.20), and 2.57 (95% CI 1.15-5.73), respectively. The associations between diabetes and common mental disorder in husbands and those same conditions in their wives were aORs = 2.28 (95% CI 1.52-3.42) and 3.01 (95% CI 2.01-4.52), respectively. Relative odds were raised even across different chronic condition phenotypes; specifically, we observed positive statistically significant associations between hypertension and obesity in the total sample of all coresiding adults (aOR = 1.24; 95% CI 1.02-1.52), high cholesterol and diabetes in the adult-parent sample (aOR = 2.02; 95% CI 1.08-3.78), and hypertension and diabetes in the spousal sample (aOR = 1.51; 95% CI 1.05-2.17). Of all associations examined, only the relationship between hypertension and diabetes in the adult-parent dyads was statistically significantly negative (aOR = 0.62; 95% CI 0.40-0.94). Relatively small samples in the dyadic analysis and site-specific analysis call for caution in interpreting qualitative differences between associations among different dyad types and geographical locations. Because of the cross-sectional nature of the analysis, the findings do not provide information on the etiology of incident chronic conditions among household members. CONCLUSIONS: We observed strong concordance of chronic conditions within coresiding adults across diverse settings in India. These data provide early evidence that a household-based approach to chronic disease research may advance public health strategies to prevent and control chronic conditions. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2013/10/004049; http://ctri.nic.in/Clinicaltrials/login.php.

One-year mortality outcomes and hospital readmissions of patients admitted with acute heart failure: Data from the Trivandrum Heart Failure Registry in Kerala, India.

BACKGROUND: There are sparse data on outcomes of patients with heart failure (HF) from India. The objective was to evaluate hospital readmissions and 1-year mortality outcomes of patients with HF in Kerala, India. METHODS: We followed 1,205 patients enrolled in the Trivandrum Heart Failure Registry for 1 year. A trained research nurse contacted each participant every 3 months using a structured questionnaire which included hospital readmission and mortality information. RESULTS: The mean (SD) age was 61.2 (13.7) years, and 31% were women. One out of 4 (26%) participants had HF with preserved ejection fraction. Only 25% of patients with HF with reduced ejection fraction received guideline-directed medical therapy at discharge. Cumulative all-cause mortality at 1 year was 30.8% (n = 371), but the greatest risk of mortality was in the first 3 months (18.1%). Most deaths (61%) occurred in patients younger than 70 years. One out of every 3 (30.2%) patients was readmitted at least once over 1 year. The hospital readmission rates were similar between HF with preserved ejection fraction and HF with reduced ejection fraction patients. New York Heart Association functional class IV status and lack of guideline-directed medical treatment after index hospitalization were associated with increased likelihood of readmission. Similarly, older age, lower education status, nonischemic etiology, history of stroke, higher serum creatinine, lack of adherence to guideline-directed medical therapy, and hospital readmissions were associated with increased 1-year mortality. CONCLUSIONS: In the Trivandrum Heart Failure Registry, 1 of 3 HF patients died within 1 year of follow-up during their productive life years. Suboptimal adherence to guideline-directed treatment is associated with increased propensity of readmission and death. Quality improvement programs aiming to improve adherence to guideline-based therapy and reducing readmission may result in significant survival benefits in the relatively younger cohort of HF patients in India.

A PROgramme of Lifestyle Intervention in Families for Cardiovascular risk reduction (PROLIFIC Study): design and rationale of a family based randomized controlled trial in individuals with family history of premature coronary heart disease.

BACKGROUND: Recognizing patterns of coronary heart disease (CHD) risk in families helps to identify and target individuals who may have the most to gain from preventive interventions. The overall goal of the study is to test the effectiveness and sustainability of an integrated care model for managing cardiovascular risk in high risk families. The proposed care model targets the structural and environmental conditions that predispose high risk families to development of CHD through the following interventions: 1) screening for cardiovascular risk factors, 2) providing lifestyle interventions 3) providing a framework for linkage to appropriate primary health care facility, and 4) active follow-up of intervention adherence. METHODS: Initially, a formative qualitative research component will gather information on understanding of diseases, barriers to care, specific components of the intervention package and feedback on the intervention. Then a cluster randomized controlled trial involving 740 families comprising 1480 participants will be conducted to determine whether the package of interventions (integrated care model) is effective in reducing or preventing the progression of CHD risk factors and risk factor clustering in families. The sustainability and scalability of this intervention will be assessed through economic (cost-effectiveness analyses) and qualitative evaluation (process outcomes) to estimate value and acceptability. Scalability is informed by cost-effectiveness and acceptability of the integrated cardiovascular risk reduction approach. DISCUSSION: Knowledge generated from this trial has the potential to significantly affect new programmatic policy and clinical guidelines that will lead to improvements in cardiovascular health in India. TRIAL REGISTRATION NUMBER: NCT02771873, registered in May 2016 ( https://clinicaltrials.gov/ct2/show/results/NCT02771873 ).

Contrasting mortality risks among subgroups of treated hypertensive patients developing new-onset diabetes.

AIMS: Hypertension and diabetes mellitus (DM) frequently cluster together and synergistically increase cardiovascular risk. Among those who develop DM during treatment for hypertension (new-onset diabetes, NOD), it is unclear whether NOD reflects a separate entity associated with increased risk or merely reflects accelerated presentation of DM. METHODS AND RESULTS: We analysed data on 15 089 hypertensive patients attending the Glasgow Blood Pressure Clinic. The date at first hospital encounter either with diagnosis of diabetes or prescription of anti-hyperglycaemic medication were considered as the onset of diabetes. Cox proportional hazard models (including propensity score matching) were employed to study associations between diabetes status, early and late NOD (diagnosis <10 years or >10 years from first clinic visit) and cause-specific mortality. There were 2516 patients (16.7%) with DM, of whom 1862 (12.3%) had NOD [early NOD = 705 (4.6%); late NOD = 1157 (7.6%)]. The incidence rate of NOD was 8.2 per 1000 person-years. The total time at risk was 239 929 person-years [median survival: 28.1 years (inter-quartile range: 16.2-39.9)]. Compared with non-diabetic individuals, prevalent DM [hazard ratio (HR) = 1.8, 95% confidence interval (CI): 1.4-2.2] and time varying NOD status (HR: 1.09, 95% CI: 1.06-1.17) were associated with increased adjusted all-cause mortality. Early NOD (HR: 1.39, 95% CI: 1.2-1.6) was associated with increased in mortality risk, but not late NOD (HR: 0.92, 95% CI: 0.83-1.01). Results were consistent in the propensity score matched analyses. CONCLUSION: Although 1-in-8 hypertensive patients develop NOD, mortality is increased only in the 1-in-20 who develop early NOD. Further studies are warranted to determine if early identification of such individuals should provide an alert for intensification of therapeutic interventions.

Task shifting of frontline community health workers for cardiovascular risk reduction: design and rationale of a cluster randomised controlled trial (DISHA study) in India.

BACKGROUND: Effective task-shifting interventions targeted at reducing the global cardiovascular disease (CVD) epidemic in low and middle-income countries (LMICs) are urgently needed. METHODS: DISHA is a cluster randomised controlled trial conducted across 10 sites (5 in phase 1 and 5 in phase 2) in India in 120 clusters. At each site, 12 clusters were randomly selected from a district. A cluster is defined as a small village with 250-300 households and well defined geographical boundaries. They were then randomly allocated to intervention and control clusters in a 1:1 allocation sequence. If any of the intervention and control clusters were <10 km apart, one was dropped and replaced with another randomly selected cluster from the same district. The study included a representative baseline cross-sectional survey, development of a structured intervention model, delivery of intervention for a minimum period of 18 months by trained frontline health workers (mainly Anganwadi workers and ASHA workers) and a post intervention survey in a representative sample. The study staff had no information on intervention allocation until the completion of the baseline survey. In order to ensure comparability of data across sites, the DISHA study follows a common protocol and manual of operation with standardized measurement techniques. DISCUSSION: Our study is the largest community based cluster randomised trial in low and middle-income country settings designed to test the effectiveness of 'task shifting' interventions involving frontline health workers for cardiovascular risk reduction. TRIAL REGISTRATION: CTRI/2013/10/004049 . Registered 7 October 2013.

Family history of premature cardiovascular disease: blood pressure control and long-term mortality outcomes in hypertensive patients.

AIMS: Current guidelines recommend early referral and initiation of intensive cardiovascular (CV) risk reduction in individuals with a positive family history of coronary heart disease (CHD). We hypothesized that a family history of premature CHD and stroke [CV disease (CVD)] would lead to earlier referral of hypertensive patients to secondary care clinic, leading to better control of risk factors, mitigating the excess risk seen in these individuals. METHODS AND RESULTS: We studied the association of a positive family history of CVD in 10 787 individuals with longitudinal changes in risk factors and long-term cause-specific mortality in the Glasgow Blood Pressure Clinic using generalized estimating equations and the Cox proportional hazard models, respectively. The total time at risk was 193 756 person-years with a median survival time of 29.2 years. A positive family history of CVD was associated with an earlier presentation to the clinic, a lower burden of traditional CV risk factors, and similar longitudinal blood pressure reduction and drug adherence compared with those without. But despite these positive features, all-cause [hazard ratio (HR) = 1.12, 95% confidence interval 1.01-1.25] and CV (HR = 1.20, 1.04-1.38) mortality independent of baseline risk factors were worse. Consistent results were observed in propensity score-matched analysis. Inclusion of family history of CVD did not improve mortality risk discrimination over and above traditional risk factors. CONCLUSION: Our study suggests that despite earlier referral and treatment of individuals with a positive family history of premature CVD, excess risk persists, indicating the need for continued and sustained efforts to reduce risk factors and drug adherence in these individuals.

Voices of care: unveiling patient journeys in primary care for hypertension and diabetes management in Kerala, India.

Background: Diabetes and hypertension are leading public health problems, particularly affecting low- and middle-income countries, with considerable variations in the care continuum between different age, socio-economic, and rural and urban groups. In this qualitative study, examining the factors affecting access to healthcare in Kerala, we aim to explore the healthcare-seeking pathways of people living with diabetes and hypertension. Methods: We conducted 20 semi-structured interviews and one focus group discussion (FGD) on a purposive sample of people living with diabetes and hypertension. Participants were recruited at four primary care facilities in Malappuram district of Kerala. Interviews were transcribed and analyzed deductively and inductively using thematic analysis underpinned by Levesque et al.'s framework. Results: The patient journey in managing diabetes and hypertension is complex, involving multiple entry and exit points within the healthcare system. Patients did not perceive Primary Health Centres (PHCs) as their initial points of access to healthcare, despite recognizing their value for specific services. Numerous social, cultural, economic, and health system determinants underpinned access to healthcare. These included limited patient knowledge of their condition, self-medication practices, lack of trust/support, high out-of-pocket expenditure, unavailability of medicines, physical distance to health facilities, and attitude of healthcare providers. Conclusion: The study underscores the need to improve access to timely diagnosis, treatment, and ongoing care for diabetes and hypertension at the lower level of the healthcare system. Currently, primary healthcare services do not align with the "felt needs" of the community. Practical recommendations to address the social, cultural, economic, and health system determinants include enabling and empowering people with diabetes and hypertension and their families to engage in self-management, improving existing health information systems, ensuring the availability of diagnostics and first-line drug therapy for diabetes and hypertension, and encouraging the use of single-pill combination (SPC) medications to reduce pill burden. Ensuring equitable access to drugs may improve hypertension and diabetes control in most disadvantaged groups. Furthermore, a more comprehensive approach to healthcare policy that recognizes the interconnectedness of non-communicable diseases (NCDs) and their social determinants is essential.

Clustering of health behaviors and their associations with cardiometabolic risk factors among adults at high risk for type 2 diabetes in India: A latent class analysis.

BACKGROUND: We aimed to identify clusters of health behaviors and study their associations with cardiometabolic risk factors in adults at high risk for type 2 diabetes in India. METHODS: Baseline data from the Kerala Diabetes Prevention Program (n = 1000; age 30-60 years) were used for this study. Information on physical activity (PA), sedentary behavior, fruit and vegetable intake, sleep, and alcohol and tobacco use was collected using questionnaires. Blood pressure, waist circumference, 2-h plasma glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standardized protocols. Latent class analysis was used to identify clusters of health behaviors, and multilevel mixed-effects linear regression was employed to examine their associations with cardiometabolic risk factors. RESULTS: Two classes were identified, with 87.4% of participants in class 1 and 12.6% in class 2. Participants in both classes had a high probability of not engaging in leisure-time PA (0.80 for class 1; 0.73 for class 2) and consuming <5 servings of fruit and vegetables per day (0.70 for class 1; 0.63 for class 2). However, participants in class 1 had a lower probability of sitting for >=3 h per day (0.26 vs 0.42), tobacco use (0.10 vs 0.75), and alcohol use (0.08 vs 1.00) compared to those in class 2. Class 1 had a significantly lower mean systolic blood pressure (ß = -3.70 mm Hg, 95% confidence interval [CI] -7.05, -0.36), diastolic blood pressure (ß = -2.45 mm Hg, 95% CI -4.74, -0.16), and triglycerides (ß = -0.81 mg/dL, 95% CI -0.75, -0.89). CONCLUSION: Implementing intervention strategies, tailored to cluster-specific health behaviors, is required for the effective prevention of cardiometabolic disorders among high-risk adults for type 2 diabetes.

Clinical exome sequencing unravels the diverse spectrum of genetic heterogeneity and genotype-phenotype correlations in hypertrophic cardiomyopathy.

BACKGROUND: Catalogues of pathogenic genetic mutations in hypertrophic cardiomyopathy (HCM) are disproportionately small when compared to that of the size of the population with South Asian ancestry and their collective increased risk of heart disease. METHODS: We conducted clinical exome sequencing of 200 HCM patients to identified cardiomyopathy-associated genetic mutations. The clinical and echocardiographic characteristics of genotype-positive and genotype-negative patients were compared, and the likelihood of detecting a positive genetic test result was evaluated. Allelic burden analysis was done to compare the minor allele frequencies (MAF) of the pathogenic or likely pathogenic (P/LP) variants and variants of uncertain significance (VUSs) identified in the cohort against various population genomics databases. RESULTS: The genetic yield was 40% for P/LP variants, with MYBPC3 and MYH7 as the predominant sarcomere genes. Younger age-at-diagnosis, family history of HCM, asymmetric hypertrophic (ASH) pattern, the ratio of the interventricular septum to posterior wall thickness (IVS/PW ratio), left atrial (LA) dimensions, severe mitral regurgitation grade (MR grade), late gadolinium enhancement (LGE) detected fibrosis and absence of hypertension were associated with an increased likelihood of HCM-associated variants. Patients who experienced ventricular tachycardia and premature cardiovascular death were significantly likely to carry MYBPC3 or loss-of-function variants. LA and interventricular septal (IVS) dimensions were associated with MYH7 variants. The rare variant burden for P/LP variants and VUSs was significantly enriched in HCM cases compared to population controls. CONCLUSION: Our study provides a comprehensive evaluation of HCM-associated genetic mutations from an Indian population. The identified genotype-phenotype associations could improve the yield of targeted genetic testing in HCM.

Experiences and challenges of people living with multiple long-term conditions in managing their care in primary care settings in Kerala, India: A qualitative study.

BACKGROUND: Multimorbidity or multiple long-term conditions (MLTCs), the coexistence of two or more chronic conditions within an individual, presents a growing concern for healthcare systems and individuals' well-being. However, we know little about the experiences of those living with MLTCs in low- and middle-income countries (LMICs) such as India. We explore how people living with MLTCs describe their illness, their engagements with healthcare services, and challenges they face within primary care settings in Kerala, India. METHODS: We designed a qualitative descriptive study and conducted in-depth, semi-structured interviews with 31 people (16 males and 15 females) from family health centres (FHCs) in Kerala. Interview data were recorded, transcribed, and thematic analysis using the Framework Method was undertaken. FINDINGS: Two main themes and three sub-themes each were identified; (1) Illness impacts on life (a)physical issues (b) psychological difficulties (c) challenges of self-management and (2) Care-coordination maze (a)fragmentation and poor continuity of care (b) medication management; an uphill battle and (c) primary care falling short. All participants reported physical and psychological challenges associated with their MLTCs. Younger participants reported difficulties in their professional lives, while older participants found household activities challenging. Emotional struggles encompassed feelings of hopelessness and fear rooted in concerns about chronic illness and physical limitations. Older participants, adhering to Kerala's familial support norms, often found themselves emotionally distressed by the notion of burdening their children. Challenges in self-management, such as dietary restrictions, medication adherence, and physical activity engagement, were common. The study highlighted difficulties in coordinating care, primarily related to traveling to multiple healthcare facilities, and patients' perceptions of FHCs as fit for diabetes and hypertension management rather than their multiple conditions. Additionally, participants struggled to manage the task of remembering and consistently taking multiple medications, which was compounded by confusion and memory-related issues. CONCLUSION: This study offers an in-depth view of the experiences of individuals living with MLTCs from Kerala, India. It emphasizes the need for tailored and patient-centred approaches that enhance continuity and coordination of care to manage complex MLTCs in India and similar LMICs.

Identification of novel endogenous control miRNAs in heart failure for normalization of qPCR data.

MicroRNAs (miRNAs), a class of non-coding RNAs, are utilized as biomarkers for a wide range of disorders. Circulating miRNAs are proposed as potential markers in the clinical identification of heart failure (HF). However, identifying miRNA biomarkers in HF requires identification of robust endogenous control miRNAs for normalization in differential expression analysis. Hence, this study aimed to identify circulating miRNAs that can be utilized as endogenous controls in HF. We evaluated the expression of eight miRNAs, which were previously reported as endogenous controls in different pathological conditions. Total RNA, including miRNA, was extracted from the serum samples of 30 HF patients (15 HFrEF and 15 HFpEF) and their matched controls (n = 15). We used quantitative PCR to determine the miRNA expression. The stability of the selected endogenous miRNAs was assessed and compared using a standard set of criteria with the RefFinder software. Six of the eight miRNAs analyzed showed consistent expression among all sample groups. Stability analysis ranked hsa-let-7i-5p, hsa-miR-148b-3p, and hsa-miR-484 as the most stable miRNAs, indicating their potential as reliable endogenous controls.

Diagnostic accuracy of diffuse reflectance imaging for early detection of pre-malignant and malignant changes in the oral cavity: a feasibility study.

BACKGROUND: Diffusely reflected light is influenced by cytologic and morphologic changes that take place during tissue transformation, such as, nuclear changes, extracellular matrix structure and composition as well as blood flow. Albeit with varying degree of sensitivity and specificity, the properties of diffusely reflected light in discriminating a variety of oral lesions have been demonstrated by our group in multiple studies using point monitoring systems. However, the point monitoring system could not identify the region with the most malignant potential in a single sitting. METHODS: In order to scan the entire lesion, we developed a multi-spectral imaging camera system that records diffuse reflectance (DR) images of the oral lesion at 545 and 575 nm with white light illumination. The diagnostic accuracy of the system for 2-dimensional DR imaging of pre-malignant and malignant changes in the oral cavity was evaluated through a clinical study in 55 patients and 23 healthy volunteers. The DR imaging data were compared with gold standard tissue biopsy and histopathology results. RESULTS: In total 106- normal/clinically healthy sites, 20- pre-malignant and 29- malignant (SCC) sites were compared. While the median pixel value of the R545/R575 image ratio for normal/clinically healthy tissue was 0.87 (IQR = 0.82-0.94), they were 1.35 (IQR = 1.13-1.67) and 2.44 (IQR = 1.78-3.80) for pre-malignant and malignant lesions, respectively. Area under the ROC curve to differentiate malignant from normal/clinically healthy [AUC = 0.99 (95% CI: 0.99-1.00)], pre-malignant from normal/clinically healthy [AUC = 0.94 (95% CI: 0.86-1.00)], malignant from pre-malignant [AUC = 0.84 (95% CI: 0.73-0.95)] and pre-malignant and malignant from normal/clinically healthy [AUC = 0.97 (95% CI: 0.94-1.00)] lesions were desirable. CONCLUSION: We find DR imaging to be very effective as a screening tool in locating the potentially malignant areas of oral lesions with relatively good diagnostic accuracy while comparing it to the gold standard histopathology.

Does uric acid qualify as an independent risk factor for cardiovascular mortality?

UA (uric acid) is the final product of purine metabolism in humans and is implicated in many disease conditions. Sustained hyperuricaemia has putative adverse roles in cardiovascular diseases. Despite strong evidence emerging from large epidemiological studies supporting the hypothesis that UA independently influences cardiovascular disease outcomes and mortality, a causal role is yet to be established. Serum UA is also considered as a useful biomarker for mortality in high-risk patients with acute coronary syndromes, heart failure and hypertension and in patients with Type 2 diabetes mellitus. Post-hoc analyses of clinical trial data suggest beneficial effects of reducing serum UA. However, these findings are inconclusive and are only hypothesis-generating. In the present issue of Clinical Science, Ndrepepa and co-workers have investigated the prognostic role of UA in high-risk Type 2 diabetic patients with established coronary artery disease in predicting 1-year survival and cardiovascular mortality. These results support the independent role of serum UA in predicting survival in Type 2 diabetic patients. However, long-term follow-up studies are required with serial UA measurement to establish the time-dependent association of UA with mortality outcomes.