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1.  Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with l-ascorbic acid1234 
Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation.
Objectives: We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations.
Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737).
Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected.
Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.
doi:10.3945/ajcn.114.092981
PMCID: PMC4266888  PMID: 25527764
l-ascorbic acid; cardiometabolic traits; confounding; genetic variants; reverse causation
2.  Exercise-based cardiac rehabilitation for coronary heart disease 
Background
The burden of coronary heart disease (CHD) worldwide is one of great concern to patients and healthcare agencies alike. Exercise-based cardiac rehabilitation aims to restore patients with heart disease to health.
Objectives
To determine the effectiveness of exercise-based cardiac rehabilitation (exercise training alone or in combination with psychosocial or educational interventions) on mortality, morbidity and health-related quality of life of patients with CHD.
Search methods
RCTs have been identified by searching CENTRAL, HTA, and DARE (using The Cochrane Library Issue 4, 2009), as well as MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), and Science Citation Index Expanded (1900 to December 2009).
Selection criteria
Men and women of all ages who have had myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA), or who have angina pectoris or coronary artery disease defined by angiography.
Data collection and analysis
Studies were selected and data extracted independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
This systematic review has allowed analysis of 47 studies randomising 10,794 patients to exercise-based cardiac rehabilitation or usual care. In medium to longer term (i.e. 12 or more months follow-up) exercise-based cardiac rehabilitation reduced overall and cardiovascular mortality [RR 0.87 (95% CI 0.75, 0.99) and 0.74 (95% CI 0.63, 0.87), respectively], and hospital admissions [RR 0.69 (95% CI 0.51, 0.93)] in the shorter term (< 12 months follow-up) with no evidence of heterogeneity of effect across trials. Cardiac rehabilitation did not reduce the risk of total MI, CABG or PTCA. Given both the heterogeneity in outcome measures and methods of reporting findings, a meta-analysis was not undertaken for health-related quality of life. In seven out of 10 trials reporting health-related quality of life using validated measures was there evidence of a significantly higher level of quality of life with exercise-based cardiac rehabilitation than usual care.
Authors’ conclusions
Exercise-based cardiac rehabilitation is effective in reducing total and cardiovascular mortality (in medium to longer term studies) and hospital admissions (in shorter term studies) but not total MI or revascularisation (CABG or PTCA). Despite inclusion of more recent trials, the population studied in this review is still predominantly male, middle aged and low risk. Therefore, well-designed, and adequately reported RCTs in groups of CHD patients more representative of usual clinical practice are still needed. These trials should include validated health-related quality of life outcome measures, need to explicitly report clinical events including hospital admission, and assess costs and cost-effectiveness.
doi:10.1002/14651858.CD001800.pub2
PMCID: PMC4229995  PMID: 21735386
*Exercise Therapy; Coronary Disease [mortality; *rehabilitation]; Health Status; Myocardial Infarction [mortality; rehabilitation]; Myocardial Revascularization [statistics & numerical data]; Outcome Assessment (Health Care); Quality of Life; Randomized Controlled Trials as Topic; Female; Humans; Male
3.  Towards a comprehensive global approach to prevention and control of NCDs 
Globalization and Health  2014;10(1):74.
Background
The “25×25” strategy to tackle the global challenge of non-communicable diseases takes a traditional approach, concentrating on a few diseases and their immediate risk factors.
Discussion
We propose elements of a comprehensive strategy to address NCDs that takes account of the evolving social, economic, environmental and health care contexts, while developing mechanisms to respond effectively to local patterns of disease. Principles that underpin the comprehensive strategy include: (a) a balance between measures that address health at the individual and population level; (b) the need to identify evidence-based feasible and effective approaches tailored to low and middle income countries rather than exporting questionable strategies developed in high income countries; (c) developing primary health care as a universal framework to support prevention and treatment; (d) ensuring the ability to respond in real time to the complex adaptive behaviours of the global food, tobacco, alcohol and transport industries; (e) integrating evidence-based, cost-effective, and affordable approaches within the post-2015 sustainable development agenda; (f) determination of a set of priorities based on the NCD burden within each country, taking account of what it can afford, including the level of available development assistance; and (g) change from a universal “one-size fits all” approach of relatively simple prevention oriented approaches to more comprehensive multi-sectoral and development-oriented approaches which address both health systems and the determinants of NCD risk factors.
Summary
The 25×25 is approach is absolutely necessary but insufficient to tackle the the NCD disease burden of mortality and morbidity. A more comprehensive approach is recommended.
doi:10.1186/s12992-014-0074-8
PMCID: PMC4215019  PMID: 25348262
Non-communicable diseases; Prevention; Health systems
4.  The Association between a Vegetarian Diet and Cardiovascular Disease (CVD) Risk Factors in India: The Indian Migration Study 
PLoS ONE  2014;9(10):e110586.
Background
Studies in the West have shown lower cardiovascular disease (CVD) risk among people taking a vegetarian diet, but these findings may be confounded and only a minority selects these diets. We evaluated the association between vegetarian diets (chosen by 35%) and CVD risk factors across four regions of India.
Methods
Study participants included urban migrants, their rural siblings and urban residents, of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore (n = 6555, mean age-40.9 yrs). Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical history, medical history, as well as blood pressure, fasting blood and anthropometric measurements were collected. Vegetarians ate no eggs, fish, poultry or meat. Using robust standard error multivariate linear regression models, we investigated the association of vegetarian diets with blood cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, fasting blood glucose (FBG), systolic (SBP) and diastolic blood pressure (DBP).
Results
Vegetarians (32.8% of the study population) did not differ from non-vegetarians with respect to age, use of smokeless tobacco, body mass index, and prevalence of diabetes or hypertension. Vegetarians had a higher standard of living and were less likely to smoke, drink alcohol (p<0.0001) and were less physically active (p = 0.04). In multivariate analysis, vegetarians had lower levels of total cholesterol (β = −0.1 mmol/L (95% CI: −0.03 to −0.2), p = 0.006), triglycerides (β = −0.05 mmol/L (95% CI: −0.007 to −0.01), p = 0.02), LDL (β = −0.06 mmol/L (95% CI: −0.005 to −0.1), p = 0.03) and lower DBP (β = −0.7 mmHg (95% CI: −1.2 to −0.07), p = 0.02). Vegetarians also had decreases in SBP (β = −0.9 mmHg (95% CI: −1.9 to 0.08), p = 0.07) and FBG level (β = −0.07 mmol/L (95% CI: −0.2 to 0.01), p = 0.09) when compared to non-vegetarians.
Conclusion
We found beneficial association of vegetarian diet with cardiovascular risk factors compared to non-vegetarian diet.
doi:10.1371/journal.pone.0110586
PMCID: PMC4208768  PMID: 25343719
5.  Omega 3 fatty acids for prevention and treatment of cardiovascular disease 
Background
It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health.
Objectives
To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies.
Search methods
Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted.
Selection criteria
RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated.
Data collection and analysis
Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data.
Main results
Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats.
Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes.
Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded.
Authors’ conclusions
It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health.
There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo.
doi:10.1002/14651858.CD003177.pub2
PMCID: PMC4170890  PMID: 15495044
*Dietary Supplements; Cardiovascular Diseases [*diet therapy; mortality; prevention & control]; Fatty Acids, Omega-3 [*therapeutic use]; Randomized Controlled Trials as Topic; Humans
6.  Psychological interventions for coronary heart disease 
Background
Psychological interventions can form part of comprehensive cardiac rehabilitation programmes (CCR). These interventions may include stress management interventions, which aim to reduce stress, either as an end in itself or to reduce risk for further cardiac events in patients with heart disease.
Objectives
To determine the effectiveness of psychological interventions, in particular stress management interventions, on mortality and morbidity, psychological measures, quality of life, and modifiable cardiac risk factors, in patients with coronary heart disease (CHD).
Search strategy
We searched CCTR to December 2001 (Issue 4, 2001), MEDLINE 1999 to December 2001 and EMBASE 1998 to the end of 2001, PsychINFO and CINAHL to December 2001. In addition, searches of reference lists of papers were made and expert advice was sought.
Selection criteria
RCTs of non-pharmacological psychological interventions, administered by trained staff, either single modality interventions or a part of CCR with minimum follow up of 6 months. Adults of all ages with CHD (prior myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina pectoris or coronary artery disease defined by angiography). Stress management (SM) trials were identified and reported in combination with other psychological interventions and separately.
Data collection and analysis
Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
Thirty six trials with 12,841 patients were included. Of these, 18 (5242 patients) were SM trials. Quality of many trials was poor with the majority not reporting adequate concealment of allocation, and only 6 blinded outcome assessors. Combining the results of all trials showed no strong evidence of effect on total or cardiac mortality, or revascularisation. There was a reduction in the number of non-fatal reinfarctions in the intervention group (OR 0.78 (0.67, 0.90), but the two largest trials (with 4809 patients randomized) were null for this outcome, and there was statistical evidence of publication bias. Similar results were seen for the SM subgroup of trials. Provision of any psychological intervention or SM intervention caused small reductions in anxiety and depression. Few trials reported modifiable cardiac risk factors or quality of life.
Authors’ conclusions
Overall psychological interventions showed no evidence of effect on total or cardiac mortality, but did show small reductions in anxiety and depression in patients with CHD. Similar results were seen for SM interventions when considered separately. However, the poor quality of trials, considerable heterogeneity observed between trials and evidence of significant publication bias make the pooled finding of a reduction in non-fatal myocardial infarction insecure.
doi:10.1002/14651858.CD002902.pub2
PMCID: PMC4170898  PMID: 15106183
*Psychotherapy; Coronary Disease [mortality; *psychology; rehabilitation]; Stress, Psychological [*therapy]; Humans
7.  Do Girls Have a Nutritional Disadvantage Compared with Boys? Statistical Models of Breastfeeding and Food Consumption Inequalities among Indian Siblings 
PLoS ONE  2014;9(9):e107172.
Background
India is the only nation where girls have greater risks of under-5 mortality than boys. We test whether female disadvantage in breastfeeding and food allocation accounts for gender disparities in mortality.
Methods and Findings
Secondary, publicly available anonymized and de-identified data were used; no ethics committee review was required. Multivariate regression and Cox models were performed using Round 3 of India’s National Family and Health Survey (2005–2006; response rate = 93.5%). Models were disaggregated by birth order and sibling gender, and adjusted for maternal age, education, and fixed effects, urban residence, household deprivation, and other sociodemographics. Mothers’ reported practices of WHO/UNICEF recommendations for breastfeeding initiation, exclusivity, and total duration (ages 0–59 months), children’s consumption of 24 food items (6–59 months), and child survival (0–59 months) were examined for first- and secondborns (n = 20,395). Girls were breastfed on average for 0.45 months less than boys (95% CI: = 0.15 months to 0.75 months, p = 0.004). There were no gender differences in breastfeeding initiation (OR = 1.04, 95% CI: 0.97 to 1.12) or exclusivity (OR = 1.06, 95% CI: 0.99 to 1.14). Differences in breastfeeding cessation emerged between 12 and 36 months in secondborn females. Compared with boys, girls had lower consumption of fresh milk by 14% (95% CI: 79% to 94%, p = 0.001) and breast milk by 21% (95% CI: 70% to 90%, p<0.000). Each additional month of breastfeeding was associated with a 24% lower risk of mortality (OR = 0.76, 95% CI: 0.73 to 0.79, p<0.000). Girls’ shorter breastfeeding duration accounted for an 11% increased probability of dying before age 5, accounting for about 50% of their survival disadvantage compared with other low-income countries.
Conclusions
Indian girls are breastfed for shorter periods than boys and consume less milk. Future research should investigate the role of additional factors driving India’s female survival disadvantage.
doi:10.1371/journal.pone.0107172
PMCID: PMC4167551  PMID: 25229235
8.  Promoting patient uptake and adherence in cardiac rehabilitation 
Background
Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programmes are below the recommended levels. This aim is to update a previous non-Cochrane systematic review which examined interventions that may potentially improve cardiac patient uptake and adherence in rehabilitation or its components and concluded that there is insufficient evidence to make specific recommendations.
Objectives
To determine the effects of interventions to increase patient uptake of, and adherence to, cardiac rehabilitation.
Search methods
A previous systematic review identified studies published prior to June 2001. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4 2007), MEDLINE (2001 to January 2008), EMBASE (2001 to January 2008), CINAHL (2001 to January 2008), PsycINFO (2001 to January 2008), Web of Science: ISI Proceedings (2001 to April 2008), and NHS Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) from 2001 to January 2008. Reference lists of identified systematic reviews and randomised control trials (RCTs) were also checked for additional studies.
Selection criteria
Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and randomised or quasi-randomised trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. Only studies reporting a measure of adherence were included.
Data collection and analysis
Titles and abstracts of all identified references were screened for eligibility by two reviewers independently and full papers of potentially relevant trials were obtained and checked. Included studies were assessed for risk of bias by two reviewers.
Main results
Ten studies were identified, three of interventions to improve uptake of cardiac rehabilitation and seven of interventions to increase adherence. Meta-analysis was not possible due to multiple sources of heterogeneity. All three interventions targeting uptake of cardiac rehabilitation were effective. Two of seven studies intended to increase adherence had a significant effect. Only one study reported the non-significant effects of the intervention on cardiovascular risk factors and no studies reported data on mortality, morbidities, costs or health care resource utilisation.
Authors’ conclusions
There is some evidence to suggest that interventions to increase the uptake of cardiac rehabilitation can be effective. Few practice recommendations for increasing adherence to cardiac rehabilitation can be made at this time. Interventions targeting patient identified barriers may increase the likelihood of success. Further high quality research is needed.
doi:10.1002/14651858.CD007131.pub2
PMCID: PMC4164451  PMID: 20614453
Angina Pectoris [rehabilitation]; Angioplasty, Balloon, Coronary [rehabilitation]; Coronary Artery Bypass [rehabilitation]; Coronary Disease [* rehabilitation]; Exercise; Heart Failure [rehabilitation]; Myocardial Infarction [rehabilitation]; Patient Acceptance of Health Care [* statistics & numerical data]; Patient Compliance [statistics & numerical data]; Randomized Controlled Trials as Topic; Adult; Humans; Middle Aged
9.  Statins for the primary prevention of cardiovascular disease 
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Search methods
To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.84, 95% CI 0.73 to 0.96) as was combined fatal and non-fatal CVD endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
Authors’ conclusions
Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of cancers or muscle pain among people without evidence of cardiovascular disease treated with statins. Other potential adverse events were not reported and some trials included people with cardiovascular disease. Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.
doi:10.1002/14651858.CD004816.pub4
PMCID: PMC4164175  PMID: 21249663
Cardiovascular Diseases [blood; *prevention & control]; Cause of Death; Cholesterol, HDL [blood]; Cholesterol, LDL [blood]; Hydroxymethylglutaryl-CoA Reductase Inhibitors [adverse effects; *therapeutic use]; Primary Prevention; Randomized Controlled Trials as Topic; Adult; Humans
10.  Exercise based rehabilitation for heart failure 
Background
The prevalence of chronic heart failure is increasing, and increases with increasing age. Major symptoms include breathlessness and restricted activities of daily living due to reduced functional capacity, which in turn affects quality of life. Exercise training has been shown to be effective in patients with coronary heart disease and has been proposed as an intervention to improve exercise tolerance in patients with heart failure.
Objectives
To determine the effectiveness of exercise based interventions compared with usual medical care on the mortality, morbidity, exercise capacity and health related quality of life, of patients with heart failure.
Search strategy
We searched the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2001), MEDLINE (2000 to March 2001), EMBASE (1998 to March 2001), CINAHL (1984 to March 2001) and reference lists of articles. We also sought advice from experts.
Selection criteria
RCTs of exercise based interventions. The comparison group was usual medical care as defined by the study, or placebo. Adults of all ages with chronic heart failure. Only those studies with criteria for diagnosis of heart failure (based on clinical findings or objective indices) have been included.
Data collection and analysis
Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information.
Main results
Twenty-nine studies met the inclusion criteria, with 1126 patients randomised. The majority of studies included both patients with primary and secondary heart failure, NYHA class II or III. Only one study specifically examined the effect of exercise training on mortality and morbidity. Exercise training significantly increased VO2 max by (WMD random effects model) 2.16 ml/kg/min (95% CI 2.82 to 1.49), exercise duration increased by 2.38 minutes (95% CI 2.85 to 1.9), work capacity by 15.1 Watts (95% CI 17.7 to 12.6) and distance on the six minute walk by 40.9 metres (95% CI 64.7 to 17.1). Improvements in VO2 max were greater for training programmes of greater intensity and duration. HRQoL improved in the seven of nine trials that measured this outcome.
Authors’ conclusions
Exercise training improves exercise capacity and quality of life in patients mild to moderate heart failure in the short term. One study found beneficial effects of exercise on cardiac mortality and hospital readmissions over 3 years of follow-up, the remaining included studies did not aim to measure clinical outcomes and were of short duration. The findings of the review are based on small-scale trials in patients who are unrepresentative of the total population of patients with heart failure. Other groups (more severe patients, the elderly, women) may also benefit. Large-scale pragmatic trials of exercise training of longer duration, recruiting a wider spectrum of patients are needed to address these issues.
doi:10.1002/14651858.CD003331.pub2
PMCID: PMC4164468  PMID: 15266480
*Exercise Therapy; Cardiac Output, Low [*rehabilitation; therapy]; Chronic Disease; Heart Failure [*rehabilitation; therapy]; Quality of Life; Randomized Controlled Trials as Topic; Humans
11.  Reduced dietary salt for the prevention of cardiovascular disease 
Background
An earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events.
Objectives
To assess the long term effects of interventions aimed at reducing dietary salt on mortality and cardiovascular morbidity.
To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes.
Search methods
The Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were searched through to October 2008. References of included studies and reviews were also checked. No language restrictions were applied.
Selection criteria
Trials fulfilled the following criteria: (1) randomised with follow up of at least six-months, (2) intervention was reduced dietary salt (restricted salt dietary intervention or advice to reduce salt intake), (3) adults, (4) mortality or cardiovascular morbidity data was available. Two reviewers independently assessed whether studies met these criteria.
Data collection and analysis
Data extraction and study validity were compiled by a single reviewer, and checked by a second. Authors were contacted where possible to obtain missing information. Events were extracted and relative risks (RRs) and 95% CIs calculated.
Main results
Six studies (including 6,489 participants) met the inclusion criteria - three in normotensives (n=3518), two in hypertensives (n=758), and one in a mixed population of normo- and hypertensives (n=1981) with end of trial follow-up of seven to 36 months and longest observational follow up (after trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR 0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97, 95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to 1.11, 565 deaths) showed no strong evidence of any effect of salt reduction. Cardiovascular morbidity in people with normal blood pressure (longest follow-up RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong evidence of benefit. We found no information on participants health-related quality of life.
Authors’ conclusions
Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.
doi:10.1002/14651858.CD009217
PMCID: PMC4160847  PMID: 21735439
*Diet, Sodium-Restricted; Cardiovascular Diseases [mortality; *prevention & control]; Randomized Controlled Trials as Topic; Sodium Chloride, Dietary [*administration & dosage]; Adult; Humans
12.  Multiple risk factor interventions for primary prevention of coronary heart disease 
Background
Primary prevention programmes in many countries attempt to reduce mortality and morbidity due to coronary heart disease (CHD) through risk factor modification. It is widely believed that multiple risk factor intervention using counselling and educational methods is efficacious and cost-effective and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions.
Objectives
To assess the effects of multiple risk factor intervention for reducing cardiovascular risk factors, total mortality, and mortality from CHD among adults without clinical evidence of established cardiovascular disease.
Search strategy
MEDLINE was searched for the original review to 1995. This was updated by searching the Cochrane Central Register of Controlled Trials on The Cochrane Library Issue 3 2001, MEDLINE(2000 to September 2001) and EMBASE (1998 to September 2001).
Selection criteria
Intervention studies using counselling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high risk groups. Trials of less than 6 months duration were excluded.
Data collection and analysis
Data were extracted by two reviewers independently. Investigators were contacted to obtain missing information.
Main results
A total of 39 trials were found of which ten reported clinical event data. In the ten trials with clinical event end-points, the pooled odds ratios for total and CHD mortality were 0.96 (95% confidence intervals (CI) 0.92 to 1.01) and 0.96 (95% CI 0.89 to 1.04) respectively. Net changes in systolic and diastolic blood pressure, and blood cholesterol were (weighted mean differences) −3.6 mmHg (95% CI −3.9 to −3.3 mmHg), −2.8 mmHg (95% CI −2.9 to −2.6 mmHg) and −0.07 mMol/l (95% CI −0.8 to −0.06 mMol/l) respectively. Odds of reduction in smoking prevalence was 20% (95% CI 8% to 31%). Statistical heterogeneity between the studies with respect to mortality and risk factor changes was due to trials focusing on hypertensive participants and those using considerable amounts of drug treatment.
Authors’ conclusions
The pooled effects suggest multiple risk factor intervention has no effect on mortality. However, a small, but potentially important, benefit of treatment (about a 10% reduction in CHD mortality) may have been missed. Risk factor changes were relatively modest, were related to the amount of pharmacological treatment used, and in some cases may have been over-estimated because of regression to the mean effects, lack of intention to treat analyses, habituation to blood pressure measurement, and use of self-reports of smoking. Interventions using personal or family counselling and education with or without pharmacological treatments appear to be more effective at achieving risk factor reduction and consequent reductions in mortality in high risk hypertensive populations. The evidence suggests that such interventions have limited utility in the general population.
doi:10.1002/14651858.CD001561.pub2
PMCID: PMC4160097  PMID: 17054138
Coronary Disease [mortality; *prevention & control]; Patient Education as Topic; Randomized Controlled Trials as Topic; Risk Factors; Humans
13.  Type of vegetarian diet, obesity and diabetes in adult Indian population 
Nutrition Journal  2014;13(1):89.
Background
To investigate the prevalence of obesity and diabetes among adult men and women in India consuming different types of vegetarian diets compared with those consuming non-vegetarian diets.
Methods
We used cross-sectional data of 156,317 adults aged 20–49 years who participated in India’s third National Family Health Survey (2005–06). Association between types of vegetarian diet (vegan, lacto-vegetarian, lacto-ovo vegetarian, pesco-vegetarian, semi-vegetarian and non-vegetarian) and self-reported diabetes status and measured body mass index (BMI) were estimated using multivariable logistic regression adjusting for age, gender, education, household wealth, rural/urban residence, religion, caste, smoking, alcohol use, and television watching.
Results
Mean BMI was lowest in pesco-vegetarians (20.3 kg/m2) and vegans (20.5 kg/m2) and highest in lacto-ovo vegetarian (21.0 kg/m2) and lacto-vegetarian (21.2 kg/m2) diets. Prevalence of diabetes varied from 0.9% (95% CI: 0.8-1.1) in person consuming lacto-vegetarian, lacto-ovo vegetarian (95% CI:0.6-1.3) and semi-vegetarian (95% CI:0.7-1.1) diets and was highest in those persons consuming a pesco-vegetarian diet (1.4%; 95% CI:1.0-2.0). Consumption of a lacto- (OR:0.67;95% CI:0.58-0.76;p < 0.01), lacto-ovo (OR:0.70; 95% CI:0.51-0.96;p = 0.03) and semi-vegetarian (OR:0.77; 95% CI:0.60-0.98; p = 0.03) diet was associated with a lower likelihood of diabetes than a non-vegetarian diet in the adjusted analyses.
Conclusions
In this large, nationally representative sample of Indian adults, lacto-, lacto-ovo and semi-vegetarian diets were associated with a lower likelihood of diabetes. These findings may assist in the development of interventions to address the growing burden of overweight/obesity and diabetes in Indian population. However, prospective studies with better measures of dietary intake and clinical measures of diabetes are needed to clarify this relationship.
doi:10.1186/1475-2891-13-89
PMCID: PMC4168165  PMID: 25192735
Vegetarian diets; Diabetes; Obesity; Men; Women; NFHS-3; India
14.  Statins and the risk of type 2 diabetes mellitus: cohort study using the UK clinical practice pesearch datalink 
Background
There is strong evidence of reductions in major vascular events from statins across all cardiovascular risk categories. However, trials of statin therapy have provided conflicting results regarding statin use and type 2 diabetes (T2DM). We aimed to assess the effect of statins on T2DM development.
Method
We carried out a population-based cohort study using the Clinical Practice Research Datalink (CPRD), a database of computerized clinical records. Every patient aged 30–85 years old starting a statin between 1989 and 2009 was matched with up to five non-statin users. The observation period in CPRD ended in 31 December 2011. Cox proportional hazard regression was used to compare rates of T2DM between statin users and non-users, using propensity score method to adjust for systematic differences between groups.
Results
The study basis comprised 2,016,094 individuals, including 430,890 people who received a statin, matched to 1,585,204 people not prescribed a statin. Mean follow-up time was 5.43 years for statin users and 3.89 years for nonusers. During follow-up 130,395 individuals developed T2DM. Statin use was associated with an increased risk of T2DM (HR 1.57; 95% CI 1.54-1.59), which increases with longer duration of use. The increased risk was smaller among people with hypertension or cardiovascular disease and was only apparent after 5 or more years treatment with statins in these groups. Conversely, age-specific risk ratios decreased in older people.
Conclusions
Statin use is associated with an increased risk of T2DM. Our results suggest that the relative risk is higher among people without diagnosed hypertension or cardiovascular disease. These findings should be considered in the context of the observational nature of the data which is prone to bias and unmeasured confounding.
doi:10.1186/1471-2261-14-85
PMCID: PMC4118294  PMID: 25022519
Statins; Type 2 diabetes; Cardiovascular; Safety; Observational
15.  Association of Common Genetic Variants with Lipid Traits in the Indian Population 
PLoS ONE  2014;9(7):e101688.
Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.
doi:10.1371/journal.pone.0101688
PMCID: PMC4081649  PMID: 24991929
16.  Nutritional profile of Indian vegetarian diets – the Indian Migration Study (IMS) 
Nutrition Journal  2014;13:55.
Background
The cardiovascular and other health benefits and potential harms of protein and micronutrient deficiency of vegetarian diets continue to be debated.
Methods
Study participants included urban migrants, their rural siblings and urban residents (n = 6555, mean age - 40.9 yrs) of the Indian Migration Study from Lucknow, Nagpur, Hyderabad and Bangalore. Information on diet (validated interviewer-administered semi-quantitative food frequency questionnaire), tobacco, alcohol, physical activity, medical histories, as well as blood pressure, fasting blood and anthropometric measurements were collected. Nutrient databases were used to calculate nutrient content of regional recipes. Vegetarians ate no eggs, fish, poultry and meat. Using multivariate linear regression with robust standard error model, we compared the macro- and micro-nutrient profile of vegetarian and non-vegetarian diets.
Results
Vegetarians, (32.8% of the population), consumed greater amounts of legumes, vegetables, roots and tubers, dairy and sugar, while non-vegetarians had a greater intake of cereals, fruits, spices, salt (p < 0.01), fats and oils. Vegetarians had a higher socioeconomic status, and were less likely to smoke, drink alcohol (p < 0.0001) and engage in less physical activity (p = 0.04). On multivariate analysis, vegetarians consumed more carbohydrates (β = 7.0 g/day (95% CI: 9.9 to 4.0), p < 0.0001), vitamin C (β = 8.7 mg/day (95% CI: 4.3 to13.0), p < 0.0001) and folate (β = 8.0 mcg/day (95% CI: 3.3 to 12.7), p = 0.001) and lower levels of fat (β = −1.6 g/day (95% CI: −0.62 to −2.7), p = 0.002), protein (β = −6.4 g/day (95% CI: −5.8 to −7.0), p < 0.0001), vitamin B12 (β = −1.4 mcg/day (95% CI: −1.2 to −1.5), p < 0.0001) and zinc (β = −0.6 mg/day (95% CI: −0.4 to −0.7), p < 0.0001).
Conclusion
Overall, Indian vegetarian diets were found to be adequate to sustain nutritional demands according to recommended dietary allowances with less fat. Lower vitamin B12 bio-availability remains a concern and requires exploration of acceptable dietary sources for vegetarians.
doi:10.1186/1475-2891-13-55
PMCID: PMC4055802  PMID: 24899080
India; Diet; Nutrition; Vegetarian; Vitamin B12
17.  Role of IGF-I, IGF-II and IGFBP-3 in lung function of males: the Caerphilly Prospective Study 
Insulin-like growth factors are peptide hormones that have an endocrine role in the development, growth and repair of human tissues including the respiratory tract. To date, only one population study exists which found positive cross-sectional associations with IGF-I and higher lung volumes. We hypothesised that higher IGF-I, IGF-II, IGFBP-3 and IGF molar ratio would be associated with better cross-sectional and longitudinal lung function. We examined cross-sectional (n=843) and prospective associations (n=717) between IGF-I, IGF-II, IGFBP-3 and IGF molar ratio with lung function in the Caerphilly Prospective Study (CaPS) from blood samples obtained around 1986, with spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)) performed in the same year and around 2003. Higher IGF molar ratio was associated with improved FEV1/FEV ratio cross-sectionally in both simple (0.007, 95% CI 0.001-0.013, P=0.02) and fully adjusted (0.001, 95% CI 0.001-0.012, P=0.03) models. With the exception of IGFBP-3 and FEV1/FVC in the simple model (0.009, 95% CI 0.001-0.018, P=0.04) all prospective associations between IGF and spirometric measures were consistent with chance. In this study of men, higher IGF molar ratio was associated with improved cross-sectional lung function, although these findings were not replicated prospectively. Further work is required with repeat IGF sampling during follow up to see if IGF levels play any role in predicting future lung function through the life course.
PMCID: PMC4065399  PMID: 24959315
Insulin-like growth factors; cohort study; spirometry; lung function
18.  Life-course determinants of bone mass in young adults from a transitional rural community in India: the Andhra Pradesh Children and Parents Study (APCAPS)123 
Background: Undernutrition and physical inactivity are both associated with lower bone mass.
Objective: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development.
Design: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987–1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009–2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18–23 y).
Results: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm2; lumbar spine: 0.86 (women), 0.93 (men) g/cm2]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories.
Conclusions: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.
doi:10.3945/ajcn.113.068791
PMCID: PMC4021785  PMID: 24695898
19.  Influence of common genetic variation on blood lipid levels, cardiovascular risk, and coronary events in two British prospective cohort studies 
European Heart Journal  2012;34(13):972-981.
Aims
The aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events.
Methods and results
Analysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women’s Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76–0.94] and 0.63 [95% CI = 0.50–0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having ‘high-risk’ status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93–1.98), BWHHS: OR = 1.49 (1.14–1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57–3.59), BWHHS: OR = 2.24 (1.52–3.29)]; and CHD events [WHII: OR = 1.43 (1.02–2.00), BWHHS: OR = 1.31 (0.99–1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score.
Conclusion
At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events.
doi:10.1093/eurheartj/ehs243
PMCID: PMC3612774  PMID: 22977227
Lipid genetic score; Lipid medication; Framingham
20.  Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals 
Background At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).
Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84–1.43) for ε2/ε2; 0.85 (95% CrI: 0.78–0.92) for ε2/ε3; 1.05 (95% CrI: 0.89–1.24) for ε2/ε4; 1.05 (95% CrI: 0.99–1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94–1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10−152), apolipoprotein B (P-trend: 8.7 × 10−06) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10−26) and HDL-C (P-trend: 1.6 × 10−12). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.
Conclusions In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
doi:10.1093/ije/dyt034
PMCID: PMC3619955  PMID: 23569189
Stroke; lipids; apolipoprotein E; cardiovascular disease; systematic review; meta-analysis; biomarkers
21.  Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis 
BMC Medicine  2014;12:51.
Background
Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials.
Methods
Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies.
Results
Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)).
Conclusions
Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.
doi:10.1186/1741-7015-12-51
PMCID: PMC3998050  PMID: 24655568
Statins; Unintended effects; Systematic review; Meta-analysis; Observational studies
22.  The Association of Early Life Supplemental Nutrition With Lean Body Mass and Grip Strength in Adulthood: Evidence From APCAPS 
American Journal of Epidemiology  2014;179(6):700-709.
In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.
doi:10.1093/aje/kwt332
PMCID: PMC3939852  PMID: 24553777
body composition; cohort study; developmental origins of health and disease; grip strength; lean body mass; muscle mass; nutrition; physical activity
23.  Hypertension among older adults in low- and middle-income countries: prevalence, awareness and control 
Background This study uses data from the World Health Organization’s Study on Global Ageing and Adult Health (SAGE) to examine patterns of hypertension prevalence, awareness, treatment and control for people aged 50 years and over in China, Ghana, India, Mexico, the Russian Federation and South Africa.
Methods The SAGE sample comprises of 35 125 people aged 50 years and older, selected randomly. Hypertension was defined as ≥140 mmHg (systolic blood pressure) or ≥90 mmHg (diastolic blood pressure) or by currently taking antihypertensives. Control of hypertension was defined as blood pressure below 140/90 mmHg on treatment. A person was defined as aware if he/she was hypertensive and self-reported the condition.
Results Prevalence rates in all countries are broadly comparable to those of developed countries (52.9%; range 32.3% in India to 77.9% in South Africa). Hypertension was associated with overweight/obesity and was more common in women, those in the lowest wealth quintile and in heavy alcohol consumers. Awareness was found to be low for all countries, albeit with substantial national variations (48.3%; range 23.3% in Ghana to 72.1% in the Russian Federation). This was also the case for control (10.2%; range 4.1% in Ghana to 14.1% India) and treatment efficacy (26.3%; range 17.4% in the Russian Federation to 55.2% in India). Awareness was associated with increasing age, being female and being overweight or obese. Effective control of hypertension was more likely in older people, women and in the richest quintile. Obesity was associated with poorer control.
Conclusions The high rates of hypertension in low- and middle-income countries are striking. Levels of treatment and control are inadequate despite half those sampled being aware of their condition. Since cardiovascular disease is by far the largest cause of years of life lost in these settings, these findings emphasize the need for new approaches towards control of this major risk factor.
doi:10.1093/ije/dyt215
PMCID: PMC3937973  PMID: 24505082
Hypertension; older people; risk factors; developing countries
24.  Is hypertension the new HIV epidemic? 
doi:10.1093/ije/dyu019
PMCID: PMC3937981  PMID: 24491955
25.  Socio-Demographic Inequalities in the Prevalence, Diagnosis and Management of Hypertension in India: Analysis of Nationally-Representative Survey Data 
PLoS ONE  2014;9(1):e86043.
Background
Hypertension is a major contributing factor to the current epidemic of cardiovascular disease in India. Small studies suggest high, and increasing, prevalence especially in urban areas, with poor detection and management, but national data has been lacking. The aim of the current study was to use nationally-representative survey data to examine socio-demographic inequalities in the prevalence, diagnosis and management of hypertension in Indian adults.
Methods
Using data on self-reported diagnosis and treatment, and blood pressure measurement, collected from 12,198 respondents aged 18+ in the 2007 WHO Study on Global Ageing and Adult Health in India, factors associated with prevalence, diagnosis and treatment of hypertension were investigated.
Results
22% men and 26% women had hypertension; prevalence increased steeply with body mass index (<18.5 kg/m2: 18% men, 21% women; 25-29.9 kg/m2: 35% men, 35% women), was higher in the least poor vs. poorest (men: odds ratio (95%CI) 1.82 (1.20 to 2.76); women: 1.40 (1.08 to 1.81)), urban vs. rural men (1.64 (1.19 to 2.25)), and men recently vs. never using alcohol (1.96 (1.40 to 2.76)). Over half the hypertension in women, and 70% in men, was undetected with particularly poor detection rates in young urban men, and in poorer households. Two-thirds of men and women with detected hypertension were treated. Two-thirds of women treated had their hypertension controlled, irrespective of urban/rural setting or wealth. Adequate blood pressure control was sub-optimal in urban men.
Conclusion
Hypertension is very common in India, even among underweight adults and those of lower socioeconomic position. Improved detection is needed to reduce the burden of disease attributable to hypertension. Levels of treatment and control are relatively good, particularly in women, although urban men require more careful attention.
doi:10.1371/journal.pone.0086043
PMCID: PMC3900470  PMID: 24465859

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