Trends in hypertension prevalence, awareness, treatment, and control: an 8-year follow-up study from rural North India.

Hypertension is a major contributor to global CVD burden. LMICs including India is challenged with rising hypertension prevalence, yet limited studies are available on temporal change and incidence among community-cohorts. This study aimed to describe trends in hypertension prevalence, awareness, treatment, and control over 8 years among a rural community-cohort from Haryana, India. The study also lends towards an analysis of incidence. Adults ≥ 30 years (N = 1542) recruited during baseline cross-sectional study between 2011 and 2014 were followed up after a median 8.1 years. At endline, demographic/lifestyle characteristics and blood pressure were re-examined. Overall median SBP significantly increased from 120 mmHg at baseline to 125.5 mmHg at endline (p < 0.001), while hypertension prevalence increased from 34.4% (95% CI 32.0-36.9) to 40.4% (95% CI 37.5-43.4) (p = 0.002). Age-standardized hypertension incidence was 30.2% (95% CI 26.7-35.2) over 8 years. Among hypertensive group, awareness, treatment, and control increased from 9.6, 8.8 and 5.0% to 31.8, 27.3 and 9.6% (p < 0.05), respectively. Increasing trend in SBP and hypertension prevalence was observed as the cohort ages. This increase is supported by the high incidence of hypertension. Nevertheless, our study highlights positive trends in hypertension care cascade but poor control, suggesting that this trend may not be adequately impactful to reduce hypertension burden.

PON1 (Paraoxonase 1) Q192R Gene Polymorphism in Ischemic Stroke among North Indian Population.

Background: PON1 is an High Density Lipoprotein (HDL)-associated esterase. Two common polymorphisms in the PON1 gene, Q192R and L55M substitutions, determine the inter-individual variation in PON1 activity. The association of these polymorphisms with the risk of ischemic stroke remains controversial. In the present study, the role of PON1 Q192R gene polymorphism in ischemic stroke was studied in the Indian population. Design and Methods: In the present case-control study, the PON1 Q192R gene polymorphism was screened in ischemic stroke patients (n: 63) and age, sex-matched controls (n: 63) using thePolymerase Chain Reaction-Restriction Segment Length Polymorphism (PCR-RFLP) method. Results: The mean age of stroke presentation was 58.11 ± 15.4 years. A total of 17.4% cases presented with young stroke (<45 years age) and 9.52% cases were seen to have a recurrent stroke. The distribution of -192Q/R PON1 gene polymorphism was not seen to differ between cases and controls. The traditional stroke risk factors did not have any effect on the PON1 genotype expression. A multivariate logistic regression analysis was done in order to assess an independent association of age, gender, traditional stroke risk factors, and PON1 polymorphism with acute ischemic stroke. However, neither the RR genotype nor the presence of the R allele was associated with an increase in the risk of acute ischemic stroke (OR [RR genotype]-4.76, P value: 0.24, 95% CI: 0.3497-64.8531; OR [R allele]-0.94, P value: 0.90, 95% CI: 0.3516-2.4989). Conclusion: PON1 Q192R gene polymorphism is not associated with an increased risk of acute ischemic stroke in the North Indian population. Further studies with a larger sample size are needed before PON1 Q192R gene polymorphism can be considered as a genetic risk factor for ischemic stroke.

Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India.

BACKGROUND: Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15µM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS: We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS: Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS: High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Methylenetetrahydrofolate reductase gene polymorphism, global DNA methylation and blood pressure: a population based study from North India.

BACKGROUND: Hypertension is a complex disorder affected by gene-environment interactions. Methylenetetrahydrofolate reductase (MTHFR) gene is one of the genes in One Carbon Metabolic (OCM) pathway that affects both blood pressure and epigenetic phenomenon. MTHFR C677T gene polymorphism leads to reduced methylation capacity via increased homocysteine concentrations. Global DNA methylation (5mC%) also gets affected in conditions such as hypertension. However, no study is found to understand hypertension in terms of both genetics and epigenetics. The present study aims to understand the relation between methylation, MTHFR C677T gene polymorphism and hypertension. It also tries to understand relation (if any) between methylation and anti-hypertensive drugs. METHODS: This is a cross-sectional study where data were collected from a total of 1634 individuals of either sex in age group 35-65 years. Hypertensives (SBP ≥ 140 mm Hg and DBP ≥ 90 mm Hg) (on treatment/not on treatment) and absolute controls were 236 (cases) and 307 (controls), respectively. All the samples were subjected to MTHFR C677T gene polymorphism screening (PCR-RFLP) and global DNA methylation assay (ELISA based colorimetric assay). Results of both the analyses were obtained on 218 cases, 263 controls. RESULTS: Median 5mC% was relatively lower among cases (p > 0.05) compared to controls, despite controlling for confounders (age, sex, smoking, alcohol, diet) (r2-0.92, p-0.08). Cases not on medication had significantly reduced 5mC% compared to controls (p < 0.05), despite adjusting for confounders (r2-0.857, p-0.01). Among cases (irrespective of treatment), there was a significant variation in 5mC% across the three genotypes i.e. CC, CT and TT, with no such variation among controls. Cases (not on medication) with TT genotype had significantly lower methylation levels compared to the TT genotype controls and cases (on medication) (p < 0.01). CONCLUSION: Global DNA hypomethylation seems to be associated with hypertension and antihypertensive drugs seem to improve methylation. Hypertensive individuals with TT genotype but not on medication are more likely to be prone to global DNA hypomethylation. Important precursors in OCM pathway include micronutrients such as vitamin B-12, B-9 and B-6; their nutritional interventions (either dietary or supplement) may serve as strategies to prevent hypertension at population level. However, more epidemiological-longitudinal studies are needed for further validation.

India Hypertension Control Initiative-Hypertension treatment and blood pressure control in a cohort in 24 sentinel site clinics.

The India Hypertension Control Initiative (IHCI) is a multi-partner initiative, implementing and scaling up a public health hypertension control program across India. A cohort of 21,895 adult hypertension patients in 24 IHCI sentinel site facilities in four Indian states (Punjab, Madhya Pradesh, Maharashtra, and Telangana), registered from January 2018 until June 2019 were assessed at baseline and then followed up for blood pressure (BP) control and antihypertensive medication use. Among all registrations, 11 274 (51%) of the patients returned for a follow-up visit between July 2019 and September 2019. Among patients returning for follow-up, 26.3% had BP controlled at registration, and 59.8% had BP controlled at follow-up (p < .001). The absolute improvement in BP control was more than two times greater in primary care (48.1 percentage point increase) than secondary care facilities (22.9 percentage point increase). Most IHCI patients received prescriptions according to state-specific treatment protocols. This study demonstrates that a scalable public health hypertension control program can yield substantial BP control improvements, especially in primary care settings. However, high loss to follow-up limits population health impact; future efforts should focus on improving systems to increase the likelihood that patients will return to the clinic for routine hypertension care.

Covid-19: a comprehensive review of a formidable foe and the road ahead.

INTRODUCTION: The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. AREAS COVERED: We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. EXPERT OPINION: The scale of the outbreak has brought the governments, health-care professionals, and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction, and aggressive steps such as 'lockdown.' Clinical trials at different phases are ongoing across different countries to expedite the development of effective drugs and vaccine to overcome the pandemic.

Prevalence of cardiovascular risk factors among tribal and non-tribal populations with East Asian Ancestry from North East India.

OBJECTIVES: The distribution of hypertension, type 2 diabetes, dyslipidemia, and obesity variables were studied among tribal and non-tribal populations with East Asian ancestry from northeast India. METHODS: Data pertaining to somatometric measurements, blood pressure, lipid profile, and fasting blood glucose were collected from 1916 participants (Mizo-422, Liangmai-352, and Meitei-1142) of both sexes older than 18 years. Two-way ANOVA and chi square analysis were done to understand the inter-population prevalence differences. RESULTS: Differential distribution of obesity variables, hypertension, type 2 diabetes, and dyslipidemia was observed among the three populations. CONCLUSIONS: Population-specific prevalence studies need to be conducted to develop population-specific health strategies, specifically in countries like India with huge diversity.

Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India.

AIM: The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism. METHODS: The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP. RESULTS HIGHER: Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts. CONCLUSION: The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.

Protein signatures linking history of miscarriages and metabolic syndrome: a proteomic study among North Indian women.

BACKGROUND: Metabolic syndrome (MeS), a constellation of metabolic adversities, and history of miscarriage make women at a higher risk for cardiovascular diseases (CVDs). However, molecular evidence indicating a link between the two phenotypes (history of miscarriage and MeS) among women would offer an opportunity to predict the risk factor for CVDs at an early stage. Thus, the present retrospective study attempts to identify the proteins signatures (if any) to understand the connection between the history of miscarriage and MeS. METHODS: Age-matched 80 pre-menopausal women who were not on any medical intervention or drugs were recruited from a Mendelian population of the same gene pool. Recruited women were classified into four groups-(a) Group A-absolute cases with history of miscarriage and MeS, (b) Group B-absolute controls without any history of miscarriage and MeS, (c) Group C-cases with MeS but lack any history of miscarriage, (d) Group D-cases with history of miscarriage but lack MeS. Differentially expressed proteins in plasma samples of women from four groups were identified using 2-D gel electrophoresis and mass spectrometry. RESULTS: Three case groups (A, C, and D) showed 18 differentially expressed proteins. Nearly 60% of proteins (11/18) were commonly dysregulated in Group C (only with MeS) and Group D (only with miscarriage history). Nearly 40% of proteins (7/18) were commonly dysregulated in the three case groups (Groups A, C, and D), indicating a shared pathophysiology. Four proteins were exclusive but shared by case groups C and D indicating the independent routes for CVDs through MeS or miscarriages. In absolute cases, transthyretin (TTR) showed exclusive upregulation, which was further validated by Western blotting and ELISA. Networking analyses showed the strong association of TTR with haptoglobin, transferrin and ApoA1 hinting toward a cross-talk among these proteins which could be a cause or an effect of TTR upregulation. CONCLUSION: The study provides evidence for molecular link between the history of miscarriage and MeS through a putative role of TTR. However, longitudinal follow-up studies with larger sample size would further help to demonstrate the significance of TTR and other targeted proteins in risk stratification and the onset of CVDs.

Association of vitamin B12 mediated hyperhomocysteinemia and methylenetetrafolate reductase (C677T) gene polymorphism with cognitive impairment: A population based study from North India.

The present study attempts to understand the association of homocysteine, vitamin B12, folate, and MTHFR C677T gene polymorphism with cognitive impairment (CI) among 808 individuals of either sex (aged 30-70 years) from a largely vegetarian, mendelian population of North India. Biochemical and genetic analyses were done using standard protocols. Results indicate that 34.3% of the subjects had mild CI, 28.7% moderate CI and 0.2% were having severe CI. Hyperhomocysteinemia was found to be a significant risk factor for moderate/severe CI. Both CT genotype and T allele of MTHFR C677T gene polymorphism were found to pose significant decreased risk for CI.

Metabolic distress in lipid & one carbon metabolic pathway through low vitamin B-12: a population based study from North India.

BACKGROUND: Dyslipidemia and hyper-homocysteinemia are the major independent risk factors of cardio vascular disease. Deficiency of folate and vitamin B-12 are associated with both hyper-homocysteinemia and dyslipidemia. The aim of the study is to evaluate the relationship of homocysteine and its associated dietary determinant levels (Folate and Vitamin B-12) with lipids and obesity parameters (WC, BMI, WHR) in North Indian population. METHODS: The participants were recruited under a major government funded project through household survey covering 15 villages of Haryana, India. Participants were both males and females, between age group 30-65 years, from a north Indian community. Initially 1634 individuals were recruited, of which 1374 were considered for analysis as they were not found to be on any kind of medication for high blood pressure, CAD, diabetes or any other disorder, and had no missing data. 5 mL of intravenous blood sample was collected after obtaining written informed consent from the participants. Homocysteine, folate and vitamin B12 levels were estimated through Immulite 1000 by chemi-luminescence technique. Triglyceride, total cholesterol and HDL-C were estimated by spectrophotometry technique using commercial kits. The values for LDL and VLDL were calculated using Friedwald's equation. Height, weight, waist circumference (WC), hip circumference (HC) was measured over light clothing. Statistical analysis for data was performed using SPSS 16.0 version. RESULTS: All the lipid indices, except HDL, showed a trend of negative correlation with homocysteine after controlling for confounders, though not significant. No association was found between obesity (WC, BMI, WHR) and homocysteine in the present study. Vitamin B-12 deficiency was significantly associated with both hyper-homocysteinemia and low HDL. Folate was found to have significantly reduced risk for high TC & LDL. CONCLUSIONS: The "hcy-lipid" hypothesis does not seem to be complementing in the present studied population. The population is vulnerable to severe under-nutrition due to the association of vitamin B-12 with HDL, leading to metabolic disturbance in both the pathways; lipid and one carbon metabolic pathway. Co-factors such as ethnicity, cultural practices, and lifestyle & dietary habits must be considered while making public health policies to control diseases.

Association of DD genotype of angiotensin-converting enzyme gene (I/D) polymorphism with hypertension among a North Indian population.

Hypertension, a major risk factor for cardiovascular diseases, is among the leading causes of morbidity and mortality worldwide. Genetic predisposition to the risk of developing hypertension due to angiotensin-converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism (through altered serum ACE activity) is well documented among various populations. The present study investigated the possible association between ACE (DD) genotype and hypertension using a nested case-control study design including 451 individuals (of either sex in the age group 30-65 years) from a rural North Indian population practicing agriculture and lacto-vegetarianism. Blood Pressure was classified using JNC-7 criterion. Age- and sex-matched individuals were selected from normotensive (N-122), pre-hypertensive (N-123), hypertensive not on medication (N-122), and hypertensive on medication (N-84) categories. Amplification of DNA and genotyping of PCR product was done using standard protocols. From the analysis, comparatively higher frequency of individuals with DD genotype in the hypertensive category was observed, indicating a possible relation between DD genotype and hypertension. The odds ratio analysis revealed 2.225 (1.13-4.37)-fold significant increased risk for hypertension among cases, validating the vulnerability of individuals with DD genotype towards hypertension. Thus, the present study highlights the increased risk for developing hypertension due to ACE DD genotype in the studied population.