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1.  Antihypertensive Treatment and Secondary Prevention of Cardiovascular Disease Events Among Persons Without Hypertension 
JAMA  2011;305(9):913-922.
Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated.
To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension.
Data Sources
Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies.
Study Selection
From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis.
Data Extraction
Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality.
Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were −7.7 (95% CI, −15.2 to −0.3) for stroke, −13.3 (95% CI, −28.4 to 1.7) for MI, −43.6 (95% CI, −65.2 to −22.0) for CHF events, −27.1 (95% CI, −40.3 to −13.9) for composite CVD events, −15.4 (95% CI, −32.5 to 1.7) for CVD mortality, and −13.7 (95% CI, −24.6 to −2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history.
Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.
PMCID: PMC4313888  PMID: 21364140
2.  Retinopathy and Cognitive Impairment in Adults With CKD 
Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small vessel disease. This relationship has not been evaluated among persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment.
Study Design
Cross-sectional study
Setting & Participants
588 participants ≥ 52 years old with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study
Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels.
Neuropsychological battery of six cognitive tests
Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy adjusting for age, race, sex, education, and medical comorbidities.
The mean age of the cohort was 65.3 +/− 5.6 (SD) years; 51.9% were non-White, and 52.6% were male. The prevalence of retinopathy was 30.1% and 14.3% for cognitive impairment. Compared to those without retinopathy, participants with retinopathy had increased likelihood of cognitive impairment on executive function (35.1% vs. 11.5%; OR, 3.4; 95% CI, 2.0-6.0), attention (26.7% vs. 7.3%; OR, 3.0; 95% CI, 1.8-4.9), and naming (26.0% vs. 10.0%; OR, 2.1; 95% CI, 1.2-3.4) after multivariable adjustment. Increased level of retinopathy was also associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment.
Unknown temporal relationship between retinopathy and impairment.
In adults with CKD, retinopathy is associated with poor performance on several cognitive domains including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.
PMCID: PMC4030670  PMID: 23206534
3.  Illicit Drug Use, Hypertension, and Chronic Kidney Disease in the U.S. Adult Population 
Illicit drug use has been associated with chronic kidney disease (CKD) in select populations but it is unknown if the same association exists in the general population. Using data from the National Health and Nutrition Examination Survey 2005-2008, we conducted a cross-sectional analysis of 5,861 adults who were questioned about illicit drug use including cocaine, methamphetamines, or heroin during their lifetime. The primary outcome was CKD as defined by an estimated glomerular filtration rate (eGFR) ≤60mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or by microalbuminuria. We also examined the association between illicit drug use and blood pressure (BP) ≥120/80, ≥130/85, and ≥140/90. Logistic regression was used to examine the association between illicit drug use and CKD and BP. Mean eGFR was similar between illicit drug users and non-users (100.7 vs. 101.4mL/min/1.73m2, p=0.4) as was albuminuria (5.7 vs. 6.0mg/g creatinine, p=0.5). Accordingly, illicit drug use was not significantly associated with CKD in logistic regression models (odds ratio [OR] 0.98, confidence interval [CI] 0.75-1.27) after adjusting for other important factors. However, illicit drug users had higher systolic (120 vs. 118mmHg, p=0.04) and diastolic BP (73 vs. 71mmHg, p=0.0003) compared to non-users. Also, cocaine use was independently associated with BP≥130/85 (OR 1.24, CI 1.00-1.54), especially when used more during a lifetime (6-49 times, OR 1.42, CI 1.06-1.91). In a representative sample of the U.S. population, illicit drug use was not associated with CKD but cocaine users were more likely to have elevated blood pressures.
PMCID: PMC3461092  PMID: 22735028
4.  Effects of Low-Carbohydrate Diets Versus Low-Fat Diets on Metabolic Risk Factors: A Meta-Analysis of Randomized Controlled Clinical Trials 
American Journal of Epidemiology  2012;176(Suppl 7):S44-S54.
The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (−14.0 mg/dL; 95% confidence interval: −19.4, −8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.
PMCID: PMC3530364  PMID: 23035144
carbohydrate-restricted diet; fat-restricted diet; meta-analysis; metabolic syndrome; obesity
5.  Physical Activity Reduces Salt Sensitivity of Blood Pressure 
American Journal of Epidemiology  2012;176(Suppl 7):S106-S113.
Salt sensitivity of blood pressure (BP) is influenced by genetic and environmental factors. A dietary feeding study was conducted from October 2003 to July 2005 that included a 7-day low-sodium intervention (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) among 1,906 individuals who were 16 years of age or older and living in rural northern China. Salt sensitivity of BP was defined as mean BP change from the low-sodium intervention to the high-sodium intervention. Usual physical activity during the past 12 months was assessed at baseline using a standard questionnaire. The multivariable-adjusted means of systolic BP responses to high-sodium intervention were 5.21 mm Hg (95% confidence interval (CI): 4.55, 5.88), 4.97 mm Hg (95% CI: 4.35, 5.59), 5.02 mm Hg (95% CI: 4.38, 5.67), and 3.96 mm Hg (95% CI: 3.29, 4.63) among participants from the lowest to the highest quartiles of physical activity, respectively (P = 0.003 for linear trend). The multivariable-adjusted odds ratio of high salt sensitivity of systolic BP was 0.66 (95% CI: 0.49, 0.88) for persons in the highest quartile of physical activity compared with those in the lowest quartile. Physical activity is significantly, independently, and inversely related to salt sensitivity of BP and may be particularly effective in lowering BP among salt-sensitive individuals.
PMCID: PMC3530366  PMID: 23035134
blood pressure; dietary sodium; physical activity; salt sensitivity
6.  Reproducibility of Blood Pressure Response to the Cold Pressor Test 
American Journal of Epidemiology  2012;176(Suppl 7):S91-S98.
An elevated blood pressure (BP) response to the cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular disease. However, it is still unclear whether BP response to the CPT is a stable and reproducible trait over time. Using the same study protocol, the authors repeated the CPT 4.5 years after initial administration among 568 Han Chinese in rural northern China (2003–2005 and 2008–2009). BP was measured using a standard mercury sphygmomanometer prior to and 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3°C–5°C) for 1 minute. Absolute BP levels and BP responses during the CPT in the initial and repeated administrations were highly correlated. For example, the correlation coefficients were 0.67, 0.73, 0.71, and 0.72 for absolute systolic BP levels at 0, 1, 2, and 4 minutes after ice-water immersion (all P 's < 0.0001). The correlation coefficients for systolic BP response were 0.41 at 0 minutes, 0.37 at 1 minute, 0.42 for maximum response, and 0.39 for the area under the curve during CPT (all P 's < 0.0001). These data indicate that BP response to the CPT is a long-term reproducible and stable characteristic in the general population.
PMCID: PMC3530368  PMID: 23035148
blood pressure; cardiovascular diseases; hypertension; reproducibility of results; stress, physiological
7.  Plant Protein Intake Is Associated with Fibroblast Growth Factor 23 and Serum Bicarbonate in Patients with CKD: The Chronic Renal Insufficiency Cohort Study 
Journal of Renal Nutrition  2012;22(4):379-388.e1.
Protein from plant, as opposed to animal, sources may be preferred in chronic kidney disease (CKD), due to lower bioavailability of phosphate and lower nonvolatile acid load.
Study Design
Observational cross-sectional study.
Setting & Participants
2938 participants with chronic kidney disease and information on dietary intake at the baseline visit in the Chronic Renal Insufficiency Cohort Study.
Percentage of total protein from plant sources (% plant protein) was determined by scoring individual food items from the National Cancer Institute Diet History Questionnaire (DHQ).
Metabolic parameters, including serum phosphate, bicarbonate (HCO3), potassium, and albumin, plasma fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and hemoglobin.
We modeled the association between % plant protein and metabolic parameters using linear regression. Models were adjusted for age, sex, race, diabetes, body mass index, eGFR, income, smoking, total energy intake, total protein intake, 24 hour urinary sodium, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and use of diuretics.
Higher % plant protein was associated with lower FGF23 (p=0.05) and higher HCO3 (p=0.01), but not with serum phosphate or PTH (p=0.9 and 0.5, respectively). Higher % plant protein was not associated with higher serum potassium (p=0.2), lower serum albumin (p=0.2) or lower hemoglobin (p=0.3). The associations of % plant protein with FGF23 and HCO3 did not differ by diabetes status, sex, race, CKD stage (2/3 vs. 4/5) or total protein intake (≤ 0.8 g/kg/d vs. >0.8 g/kg/d) (p-interaction > 0.10 for each).
Cross-sectional study; Determination of % plant protein using the DHQ has not been validated.
Consumption of a higher percentage of protein from plant sources may lower FGF23 and raise HCO3 in patients with CKD.
PMCID: PMC3383455  PMID: 22480598
chronic kidney disease; nutrition; mineral metabolism; acidosis
8.  Predictors of Condom Use Behaviors Based on the Health Belief Model (HBM) among Female Sex Workers: A Cross-Sectional Study in Hubei Province, China 
PLoS ONE  2012;7(11):e49542.
HIV infection related to commercial sexual contact is a serious public health issue in China. The objectives of the present study are to explore the predictors of condom use among female sex workers (FSWs) in China and examine the relationship between Health Belief Model (HBM) constructs.
Methodology/Principal Findings
A cross-sectional study was conducted in two cities (Wuhan and Suizhou) in Hubei Province, China, between July 2009 and June 2010. A total of 427 FSWs were recruited through mediators from the ‘low-tier’ entertainment establishments. Data were obtained by self-administered questionnaires. Structural equation models were constructed to examine the association. We collected 363 valid questionnaires. Within the context of HBM, perceived severity of HIV mediated through perceived benefits of condom use had a weak effect on condom use (r = 0.07). Perceived benefits and perceived barriers were proximate determinants of condom use (r = 0.23 and r = −0.62, respectively). Self-efficacy had a direct effect on perceived severity, perceived benefits, and perceived barriers, which was indirectly associated with condom use behaviors (r = 0.36).
The HBM provides a useful framework for investigating predictors of condom use behaviors among FSWs. Future HIV prevention interventions should focus on increasing perceived benefits of condom use, reducing barriers to condoms use, and improving self-efficacy among FSWs.
PMCID: PMC3502447  PMID: 23185355
9.  Obesity and Left Ventricular Dilatation in Young Adulthood: The Bogalusa Heart Study 
Clinical cardiology  2011;34(3):153-159.
Background and Aims
Cardiac enlargement is an important predictor of adverse cardiovascular (CV) events. LV dilatation is a precursor both of LV dysfunction and clinical heart failure. The present study examines risk factors for left ventricular (LV) dilatation among 832 young adults (341 male, 491 female) who participated in the Bogalusa Heart Study.
Methods and Results
Standard ventricular dimensions were determined by M-mode echocardiography and indexed to height using a standard method. LV dilatation was considered as the top 20th percentile of LV end-diastolic dimension indexed to height. Logistic regression models were used, stratified by race and sex, to assess the relationship of CV risk factors with quintile of LV end-diastolic dimension indexed to height. The mean age (SD) of men and women in the population was 36.4 (3.9) and 35.9 (4.6), respectively. In sex-specific models adjusted for age, race, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and glycosylated hemoglobin, body mass index (BMI) was a significant predictor of LV dilatation in both men and women. The odds ratio (95% confidence interval) for a one unit change in BMI was 1.12 (1.02 to 1.19) in men and 1.09 (1.05 to 1.13) in women. Among men, triglyceride level was also significantly associated with LV dilatation (p=0.03), whereas among women, there was no such association.
Our findings indicate that obesity is the most consistent predictor of LV dilatation in both men and women, while triglyceride level was a significant predictor among men only.
PMCID: PMC3077044  PMID: 21400542
cardiovascular diseases; risk factor; ventricular remodeling; heart failure
10.  Non-Soy Legume Consumption Lowers Cholesterol Levels: A Meta-Analysis of Randomized Controlled Trials 
Background and Aims
Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids.
Methods and Results
Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was −11.8 mg/dL (95% confidence interval [CI], −16.1 to −7.5); mean net change in low density lipoprotein cholesterol was −8.0 mg/dL (95% CI, −11.4 to −4.6).
These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.
PMCID: PMC2888631  PMID: 19939654
legumes; fabaceae; meta-analysis; randomized controlled trial; cholesterol; cardiovascular diseases
11.  Association of inflammation and endothelial dysfunction with metabolic syndrome, prediabetes and diabetes in adults from Inner Mongolia, China 
We examined the association of biomarkers of inflammation and endothelial dysfunction with diabetes and metabolic syndrome (MetS) in persons from Inner Mongolia.
A cross-sectional study was conducted among 2,536 people aged 20 years and older from Inner Mongolia, China. Overnight fasting blood samples were obtained to measure plasma concentrations of high sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), sE-selectin, angiotensin II, high density lipoprotein cholesterol, triglycerides, and blood glucose. Waist circumference and blood pressure were measured by trained staff. MetS was defined according to the modified ATP III definition for Asians. Elevated level of the biomarker was defined as values in the upper tertile of the distribution. Participants were categorized into one of four groups based on the presence or absence of metabolic and glycemic abnormalities: 1) free of prediabetes, diabetes and MetS (reference group), 2) prediabetes or diabetes only, 3) MetS without prediabetes or diabetes, and 4) MetS plus prediabetes or diabetes. The multivariable models are adjusted for age, gender, smoking, drinking, family history of hypertension, and body mass index.
Among study participants, 18.5% had prediabetes, 3.6% had diabetes, and 27.4% of the entire study population had 3 or more components of the MetS. Elevated hsCRP was associated with an increased odds of prediabetes or diabetes only, MetS without prediabetes or diabetes, and MetS plus prediabetes or diabetes with multivariable adjusted odds ratios (95% confidence intervals) of 2.3 (1.7-3.1), 3.0 (2.4-3.8), and 5.8 (4.5-7.5), respectively. Elevated sICAM-1 was associated with increased odds (95% CI) of prediabetes or diabetes only (2.1, 1.6-2.9) and MetS plus prediabetes or diabetes (4.2, 3.2-5.3) but was not associated with MetS alone. Elevated sE-selectin was associated with a modestly increased risk of MetS (OR 1.7, 95% CI 1.4-2.2). Elevated levels of Angiotensin II were not associated with the MetS plus prediabetes or diabetes in this study.
Diabetes and the MetS are common in the Inner Mongolia population. The biomarkers of inflammation and endothelial dysfunction are associated with increased risk for diabetes and MetS in this population. These results are consistent with results from other populations.
PMCID: PMC3204247  PMID: 21989115
metabolic syndrome; diabetes; inflammation; endothelial dysfunction; C-reactive protein; intercellular adhesion molecule-1; E-selectin
12.  Chronic Kidney Disease and Prevalent Atrial Fibrillation: The Chronic Renal Insufficiency Cohort (CRIC) 
American heart journal  2010;159(6):1102-1107.
The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease (ESRD), with limited data on less advanced chronic kidney disease (CKD) stages.
A total of 3267 adult participants (50% non-Hispanic blacks, 46% females) with CKD from the Chronic Renal Insufficiency Cohort (CRIC) were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (N=323) or those without ECG data (N=22) were excluded. AF was ascertained by a 12-lead electrocardiogram (ECG) and self-report. Age- sex- race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable adjusted logistic regression analysis.
The mean estimated glomerular filtration rate (GFR) was 43.6 (±13.0) ml/min/1.73 m2. AF was present in 18% of the study population and in more than 25% of those 70 years or older. In multivariable adjusted models, 1-SD increase in age (11 years) [odds ratio (OR) and CI 95%: 1.27 (1.13, 1.43), P<0.0001], female sex [0.80 (0.65, 0.98), P=0.0303], smoking (former vs. never) [1.34 (1.08, 1.66), P= 0.0081], history of heart failure [3.28 (2.47, 4.36), P<0.001], and history of cardiovascular disease [1.94 (1.56, 2.43), P<0.0001] were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated GFR <45 ml/min/1.73 m2 was associated with AF in an unadjusted model [1.35 (1.13–1.62)); P=0.0010)], but not after multivariable adjustment [1.12 (0.92– 1.35), P=0.2710].
Nearly one in five participants in CRIC, a national study of CKD, had evidence for AF at study entry, a prevalence similar to that reported among patients with ESRD and 2–3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.
PMCID: PMC2891979  PMID: 20569726
13.  Detection and follow-up of chronic obstructive pulmonary disease (COPD) and risk factors in the Southern Cone of Latin America. the pulmonary risk in South America (PRISA) study 
The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition.
PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken.
There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary disease, patient characteristics and changes in lung function over time as well as quality of life and health care resource utilization. Information gathered during the PRISA Study will inform public health interventions and prevention practices to reduce risk of COPD in the region.
PMCID: PMC3116480  PMID: 21627849
Chronic Obstructive Pulmonary Disease; Risk Factors; South America; Cohort
14.  Detection and follow-up of cardiovascular disease and risk factors in the Southern Cone of Latin America: the CESCAS I study 
BMJ Open  2011;1(1):e000126.
Cardiovascular diseases (CVD) are increasing throughout the world and cause 16.7 million deaths each year, 80% of which occur in low and middle income countries. In Argentina, Chile and Uruguay, the available data on cardiovascular risk factors come predominantly from cross-sectional studies that are principally based on self-report or studies conducted with small convenience samples. The CESCAS I study will generate reliable estimates of the prevalence and distribution of and secular trends in CVD and its risk factors in this region.
Methods and analysis
CESCAS I is an observational prospective cohort study with a multistage probabilistic sample of 8000 participants aged 35–74 years from four mid-sized cities representing the Southern Cone of Latin America: Bariloche and Marcos Paz in Argentina, Temuco in Chile and Pando-Barros Blancos in Uruguay. In the first phase, baseline data regarding exposure to risk factors and prevalence of CVD will be collected in two stages: (1) in homes and (2) in health centres. Information will be gathered on medical history, risk factors, lifestyles and health utilisation through specific questionnaires, physical measurements, an ECG and an overnight, fasting blood sample to measure levels of serum lipids, glucose and creatinine. In the second phase, annual follow-up data will be obtained on the incidence rate of CVD events and the association between exposure and events.
Ethics and dissemination
The protocol has obtained formal ethics approval from institutional review boards in Argentina, Chile, Uruguay and the USA. The lack of follow-up studies has prevented Argentina, Chile and Uruguay from implementing risk factor stratification and management strategies at a population level. However, the CESCAS I study data will help the development of public health strategies based on primary care intervention, thus helping to improve cardiovascular health in this region.
Article summary
Article focus
To estimate the prevalence and distribution of and secular trends in major cardiovascular disease (CVD) events and risk factors in four cities in Argentina, Chile and Uruguay.
Key messages
Lack of follow-up studies prevents Argentina, Chile and Uruguay from assessing local risk estimates, obtaining reliable data on CVD burden and implementing risk factor stratification and management strategies at a population level.
There is a strong need in the region to build the capacity and infrastructure to undertake a population-based cohort study to address knowledge gaps and to inform policymakers of the impact of CVD in the Southern Cone of Latin America.
Strengths and limitations of this study
CESCAS I will be the first longitudinal study to estimate the CVD trend and risk factors in Argentina, Chile and Uruguay.
PMCID: PMC3191438  PMID: 22021769
15.  Glucose Control and Cardiovascular Disease in Type-2 Diabetes: A Meta-Analysis 
Annals of internal medicine  2010;152(1):63-64.
Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting.
To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type-2 diabetes.
Data Sources
Studies were retrieved by systematically searching the MEDLINE database (January 1950-April 2009) with no language restrictions.
Study Selection
Two independent reviewers screened abstracts or full text articles to identify randomized trials comparing clinical outcomes in type-2 diabetes patients treated with intensive compared to conventional glucose control.
Data Extraction
Two investigators independently abstracted data on study variables and outcomes including severe hypoglycemia, cardiovascular disease, and all-cause mortality.
Data Synthesis
Five trials involving 27,802 adults were included. Intensive glucose targets were lower in the three most recent trials. Summary analyses showed that, compared with conventional control, intensive glucose control reduced the risk of cardiovascular disease (relative risk (RR): 0.90, 95% confidence interval (CI): 0.83, 0.98; risk difference per 1,000 patients per 5 years (RD): -15, CI: -24, -5) but not cardiovascular death (RR: 0.97, CI: 0.76, 1.24; RD: -3, CI: -14, 7) or all-cause mortality (RR: 0.98, CI: 0.84, 1.15; RD: -4, CI: -17, 10) and increased the risk of severe hypoglycemia (RR: 2.03, CI: 1.46, 2.81; RD: 39, CI: 7, 71). Similar to overall analyses, intensive glucose control reduced risk of cardiovascular disease and increased risk of severe hypoglycemia in pooled findings from early and more recent trials.
Summary rather than individual data were pooled across trials.
Intensive glucose control reduced risk for some cardiovascular disease (e.g., non-fatal myocardial infarction), but did not reduce risk for cardiovascular or all-cause mortality and increased risk of severe hypoglycemia.
PMCID: PMC3058557  PMID: 20048277
intensive glucose control; cardiovascular disease; mortality; relative risk; randomized controlled trials; meta-analysis
16.  Mortality from suicide and other external cause injuries in China: a prospective cohort study 
BMC Public Health  2011;11:56.
Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China.
A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded.
Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29-3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries.
External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted.
PMCID: PMC3039589  PMID: 21269516
17.  Correlation between Blood Pressure Responses to Dietary Sodium and Potassium Intervention in a Chinese Population 
American journal of hypertension  2009;22(12):1281-1286.
Blood pressure (BP) responses to dietary sodium and potassium intake vary among individuals. We examined the correlation between BP responses to dietary low-sodium, high-sodium, and potassium supplementation interventions in a feeding study.
1,906 Chinese aged ≥16 years participated in the dietary intervention which included a 7-day low-salt intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention. BP was measured 9 times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer.
The correlation coefficients (95% confidence intervals [CI]) of the BP responses to low-sodium and high-sodium intervention were −0.47 (−0.51 to −0.44), −0.47 (−0.50 to −0.43), and −0.45 (−0.49 to −0.42) for systolic, diastolic, and mean arterial pressure (MAP), respectively (all p<0.0001). The correlation coefficients (95% CI) of the BP responses to high-sodium intervention and potassium supplementation were −0.52 (−0.56 to −0.49), −0.48 (−0.52 to 0.45), and −0.52 (−0.55 to −0.48) for systolic, diastolic, and MAP, respectively (all p <0.0001). The kappa coefficients were moderate, varying from 0.28 to 0.34, between BP responses to low-sodium and high-sodium intervention (all p <0.0001).
These results indicate there is a moderate correlation between BP responses to low-sodium and to high-sodium interventions, and BP responses to high-sodium intervention and potassium supplementation. Furthermore, our study suggests that individuals who were more sensitive to high-sodium diet might benefit more from a low-sodium and/or high-potassium intervention aimed at lowering BP levels.
PMCID: PMC2885718  PMID: 19763120
18.  Alcohol Consumption and Risk of Coronary Heart Disease among Chinese Men 
Observational studies suggest that moderate alcohol consumption may lower risk of myocardial infarction (MI) and coronary heart disease (CHD); yet, evidence for this comes almost entirely from Western populations.
We conducted a prospective cohort study in 64,597 Chinese men aged ≥40 years who were free of clinical CHD at baseline examination. Data on frequency and type of alcohol consumed were collected at the baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999–2000, with a response rate of 94%.
Over 494,084 person-years of follow-up, we documented 725 (361 fatal) incident MI and 976 (588 fatal) incident CHD events. After stratification by province to account for multi-stage sampling design and adjustment for age, education, physical activity, cigarette smoking, body mass index, systolic blood pressure, urbanization (urban vs. rural), geographic variation (north vs. south) and history of diabetes, relative risk (95% confidence interval) of MI was 0.93 (0.70–1.24) for participants consuming 1 to 6 drinks/week, 0.66 (0.54–0.82) for those consuming 7 to 34 drinks/week, and 0.58 (0.41–0.81) for those consuming ≥35 drinks/week (P for linear trend <0.0001) compared to non-drinkers. The corresponding relative risks for CHD events were 0.99 (0.77–1.27), 0.67 (0.56–0.81), and 0.58 (0.44–0.78), respectively (P for linear trend <0.0001).
Alcohol consumption may be related to lower risk of MI and CHD in middle-aged and older Chinese men. However, heavy alcohol consumption may lead to increased mortality from other causes; therefore, the implications of these findings should be interpreted cautiously.
PMCID: PMC2726155  PMID: 18614248
Myocardial Infarction; Coronary Heart Disease; Alcohol Drinking, Risk Factor; Prospective Studies; Cohort Studies; Men
19.  Gender Difference in Blood Pressure Responses to Dietary Sodium Intervention in the GenSalt Study 
Journal of hypertension  2009;27(1):48-54.
To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions.
We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention among 1,906 study participants in rural China. BP was measured 9 times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer.
BP responses to low-sodium intervention were significantly greater in women compared to men: –8.1 (95% confidence interval (−8.6 to −7.6) versus −7.0 (−7.5 to −6.6) mmHg for systolic and −4.5 (−4.9 to −4.1) versus −3.4 (−3.8 to −3.0) mmHg for diastolic. Likewise, BP responses to high-sodium interventions were significantly greater in women compared to men: 6.4 (5.9 to 6.8) versus 5.2 (4.8 to 5.7) mmHg for systolic and 3.1 (2.7 to 3.5) versus 1.7 (1.4 to 2.1) mmHg for diastolic (all p<0.001). In addition, systolic BP responses to the sodium interventions increased with age and both systolic and diastolic BP responses to the sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels.
These results suggest that female gender, older age, and hypertension increase sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.
PMCID: PMC2882679  PMID: 19145767
20.  Novel Genetic Variants in the Alpha-adducin and Guanine Nucleotide Binding Protein Beta Polypeptide 3 Genes and Salt-Sensitivity of Blood Pressure 
American journal of hypertension  2009;22(9):985-992.
We examined the association between twelve single nucleotide polymorphisms (SNPs) in the alpha-adducin (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) pressure responses to salt-intake.
A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Han participants from rural north China. BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer.
We identified a significant association between a rare ADD1 variant rs17833172 and SBP, DBP, and MAP responses to high-sodium (p-values<0.0001) and DBP response to low-sodium (p-value=0.002). Participants homozygous for the variant A allele of this marker had SBP, DBP, and MAP responses (95% confidence interval) to high-salt of 1.6 (−1.8, 4.9), −0.8 (−5.6, 4.0), and −0.1 (−4.0, 3.9) mmHg, respectively, versus corresponding responses of 4.6 (2.5, 6.6), 1.7 (−0.2, 3.6), and 2.7 (0.9, 4.4) mmHg, respectively, for those who were heterozygous or homozygous for the G allele. In addition, participants with at least one copy of the A allele of SNP rs1129649 of the GNB3 gene had significantly decreased MAP response to low-salt compared to homozygotes for the C allele (p-value=0.004) with responses of −3.4 (−3.8, −3.0) versus −4.2 (−4.6, −3.8) mmHg, respectively.
These data support a role for the ADD1 and GNB3 genes in BP salt-sensitivity. Future studies aimed at replicating these novel findings are warranted.
PMCID: PMC2882159  PMID: 19574959
blood pressure; genetics; polymorphism; dietary sodium; salt sensitivity; ADD1; GNB3
21.  Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women  
Diabetes Care  2008;31(7):1311-1317.
OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported.
RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]).
CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.
PMCID: PMC2453647  PMID: 18390796

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