Lydia A. Bazzano

Effect of Nocturnal Nasal Continuous Positive Airway Pressure on Blood Pressure in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a very common risk factor for hypertension, and continuous positive airway pressure (CPAP) has been widely used to treat OSA. We conducted a meta-analysis of randomized, controlled trials to evaluate the effects of CPAP on blood pressure, reported as either a primary or secondary end point, among patients with OSA. Studies were retrieved by searching Medline (January 1980 to July 2006), the Cochrane Database of Systematic Reviews, conference abstracts, and bibliographies of review and original articles. From 255 relevant reports, 16 randomized clinical trials were selected that compared CPAP to control among participants with OSA, had a minimum treatment duration of 2 weeks, and reported blood pressure changes during the intervention or control period. 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 16 trials representing 818 participants were examined using a random-effects model. Mean net change in systolic blood pressure for those treated with CPAP compared with control was −2.46 mm Hg (95% CI: −4.31 to −0.62); mean net change in diastolic blood pressure was −1.83 mm Hg (95% CI: −3.05 to −0.61); and mean net change in mean arterial pressure was −2.22 mm Hg (95% CI: −4.38 to −0.05). Net reductions in blood pressure were not statistically different between daytime and nighttime. These results indicate that CPAP decreases blood pressure among those with OSA and may help prevent hypertension.

Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States.

Context Recently identified risk factors for cardiovascular disease include acute phase reactants and elevated homocysteine levels. How are these newer risk factors related to a classic risk factor, cigarette smoking? Contribution This large population-based study showed strong, positive, independent, and doserelated relationships between cigarette smoking and elevated levels of C-reactive protein, fibrinogen, and homocysteine. Implications Smoking may promote atherosclerosis through inflammation and hyperhomocysteinemia. Cautions The study was cross-sectional and did not definitively establish causal or temporal relationships. The Editors Cardiovascular disease is the leading cause of death worldwide (1). In the United States, cardiovascular death accounted for approximately 40% (958 775) of all deaths in 1999 (2). Cigarette smoking is a major modifiable risk factor for cardiovascular disease, including coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure (3, 4). In 1990, an estimated 20% of deaths from cardiovascular disease could be attributed to cigarette smoking in the United States (5). The relationship between cigarette smoking and many established risk factors for cardiovascular disease has been studied. Cigarette smoking has been associated with higher serum levels of cholesterol, coronary vasomotor reactivity, platelet aggregation, and a prothombotic state (6-9). However, few data are available on the relationship between cigarette smoking and newly emerging risk factors for cardiovascular disease (10-13). We used the large sample size and representative nature of the Third National Health and Nutrition Examination Survey (NHANES III) to examine the relationship between cigarette smoking status and novel risk factors for cardiovascular disease, including serum C-reactive protein, fibrinogen, and homocysteine levels. Methods Study Sample The NHANES III was conducted by the National Center for Health Statistics from 1988 to 1994. The details of study participants and methods have been published elsewhere (14). In brief, the NHANES III used a stratified, multistage, cluster-sampling design to select a representative sample of the U.S. civilian noninstitutionalized population age 2 months and older (14). Of the 19 618 NHANES III participants at least 18 years of age, 18 participants who were missing smoking information were excluded from our analysis. An additional 3004 participants who lacked information on C-reactive protein were excluded, which left 16 596 participants for this analysis. Fibrinogen levels were measured among participants at least 40 years of age; 2082 persons were missing values for fibrinogen, leaving 9350 persons available for this analysis. Homocysteine levels were collected between 1991 and 1994 (during phase 2 of the NHANES III), and 1469 persons were missing values for homocysteine, which left 7458 persons available for this analysis. Participants missing information for C-reactive protein, fibrinogen, or homocysteine levels tended to be older and more often non-Hispanic white or non-Hispanic black than Mexican-American. Sex distribution and smoking status did not differ between those participants with missing values and those included in this analysis. Measurements The NHANES III data collection included a home interview and a detailed clinical examination in a mobile examination center. Ever smoking cigarettes was defined by self-report of having smoked at least 100 cigarettes in a participants lifetime. Current cigarette smoking was defined by answering yes to the question: Do you smoke cigarettes now? Information on medical history and current use of estrogen replacement therapy, aspirin, and physical activity were also collected during the home interview. Diabetes mellitus was defined by self-report of a physician diagnosis. Blood pressure was measured three times during the home interview and three times during the clinical examination by using a standard mercury sphygmomanometer with the participant seated. A participants mean blood pressure was calculated by using all available systolic and diastolic readings. Anthropometric measures, such as body weight, height, and waist and hip circumferences, were also obtained. Blood samples were drawn during the clinical examination. Laboratory procedures used in the NHANES III are described elsewhere (15). Briefly, serum cotinine level was measured by using high-performance liquid chromatography atmospheric-pressure chemical ionization tandem mass spectrometry (16). A serum cotinine level of 56.8 nmol/L (10 ng/mL) or higher was used as a marker of current cigarette smoking (17). Serum C-reactive protein level was measured by using latex-enhanced nephelometry (15). Because 74% of individuals had C-reactive protein levels below the detection limit for this assay (2.2 mg/L), C-reactive protein level was categorized as undetectable (<2.2 mg/L), detectable (2.2 to 9.9 mg/L), and clinically elevated ( 10 mg/L) (18). Serum homocysteine level was measured by using high-performance liquid chromatography (19). Fibrinogen level was measured for participants 40 years of age or older by using enzyme assay methods (20). Fibrinogen and homocysteine levels were defined as elevated if values were in the 85th percentile or greater (11.1 mol/L and 12.7 mmol/L, respectively) for this nationally representative population. Statistical Analysis The mean or percentage of each characteristic was calculated by self-reported smoking status (current, former, or never) and standardized to the age, ethnicity, and sex distribution of the overall U.S. population. The statistical significance of differences among groups was examined by using the Wald test (categorical variables) and analysis of covariance (continuous variables). Associations between smoking status, with never-smokers as the reference category, and elevated serum C-reactive protein, fibrinogen, and homocysteine levels were examined by using two logistic regression models. We first determined the odds ratios of elevated levels of the novel risk factors associated with cigarette smoking adjusted for age, ethnicity, and sex only. In the second model, odds ratios were also adjusted for diabetic status, hormone replacement therapy, body mass index, waisthip ratio, systolic blood pressure, serum total cholesterol level, leisure time physical activity, and use of aspirin in the past month. Doseresponse relationships for current smokers were examined by using never-smokers as the reference category compared with current cigarette smoking by three levels of daily cigarette consumption and tertiles of pack-year smoking history. For doseresponse analysis using cotinine, levels below 56.8 nmol/L (10 ng/mL) were used as the reference category and levels above 56.8 nmol/L (10 ng/mL), tertiles of cotinine. To account for the complex survey design, we used Stata softwares survey data commands (svy) (Stata Corp., College Station, Texas) and applied NHANES III weights to all analyses. Role of the Funding Source The funding source had no role in the design, conduct, and reporting of the study or in the decision to submit the manuscript for publication. Results Characteristics of the 19 600 participants available for analysis are displayed by smoking status in Table 1. Serum cotinine, detectable C-reactive protein, clinically elevated C-reactive protein, fibrinogen, and homocysteine levels were higher among current smokers than former smokers and never-smokers. The median time since smoking cessation for former smokers in this study sample was 10 years (interquartile range, 3 to 20 years). Table 1. Characteristics of Self-Reported Cigarette Smoking for 19600 Participants in the Third National Health and Nutrition Examination Survey Odds ratios and 95% CIs for detectable and clinically elevated C-reactive protein, elevated fibrinogen, and elevated homocysteine levels are presented in Table 2. Participants who self-reported former or current cigarette smoking had a significantly higher odds of having elevated levels of all novel risk factors in age-, ethnicity-, sex-adjusted models and multivariate-adjusted models than participants who reported never smoking cigarettes; the exception was homocysteine levels in former smokers. For example, self-reported current cigarette smoking was associated with having a serum C-reactive protein level in the detectable (odds ratio, 1.66 [95% CI, 1.40 to 1.97]; P < 0.001) or clinically elevated (odds ratio, 1.98 [CI, 1.57 to 2.51]; P < 0.001, respectively) ranges, an elevated fibrinogen level (odds ratio, 2.15 [CI, 1.65 to 2.80]; P < 0.001), and an elevated homocysteine level (odds ratio, 2.10 [CI, 1.62 to 2.74]; P < 0.001) as compared with never smoking cigarettes in multivariate-adjusted analyses. Similar results were obtained when participants were categorized by serum cotinine level. All analyses were repeated by using participants who had not reported previous cardiovascular disease; little difference was seen. Significance levels of all effect estimates remained less than 0.001 for both self-reported current cigarette smoking and cotinine levels of 56.8 nmol/L (10 ng/mL) or greater. Table 2. Odds Ratios and 95% CIs for Detectable or Clinically Elevated C-Reactive Protein, Fibrinogen, and Homocysteine Levels by Self-Reported Smoking Status and Serum Cotinine Level Table 3 shows the odds ratios and 95% CIs for detectable and clinically elevated C-reactive protein, elevated fibrinogen, and elevated homocysteine levels by number of cigarettes smoked per day, pack-year smoking history, and serum cotinine levels. Number of cigarettes smoked per day was significantly and positively related to elevated levels of all novel risk factors in both age-, ethnicity-, sex-adjusted models and multivariate-adjusted models. The same was true for tertiles of pack-years and tertiles of cotinine levels above 56.8 nmol/L (10 ng/mL). Table 3. Odds Ratios and 95%

Systematic review: glucose control and cardiovascular disease in type 2 diabetes.

Context The relative benefits and harms of intensive versus conventional glucose control for type 2 diabetes are controversial. Contribution This review of 5 large trials found that, compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (mostly nonfatal myocardial infarction) but not for cardiovascular death or all-cause mortality, and increased risk for severe hypoglycemia. Trial design, achieved control, and findings were heterogeneous: Early trials suggested possible decreased risk for death with intensive control, whereas some more recent trials suggested possible increased risk for death with more stringent control. Caution The investigators did not evaluate costs. They pooled summary findings from trials rather than individual data from patients. The Editors The prevalence of type 2 diabetes is increasing globally (13). Epidemiologic evidence indicates that diabetes is a major risk factor for cardiovascular disease (CVD), and recent data suggest that the CVD burden attributable to diabetes is on the rise (47). Clinical trials have shown that intensive glucose control reduces the risk for microvascular complications among patients with type 2 diabetes, but its effect on CVD, including coronary heart disease (CHD), stroke, and peripheral arterial disease, is uncertain (810). Early data from the UKPDS (United Kingdom Prospective Diabetes Study) 34 suggested a protective effect of improved glucose control on CVD, CVD deaths, and all-cause mortality (11). However, within the past year, 3 large randomized, controlled trials have reported conflicting results (1214). Although ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) and VADT (Veterans Affairs Diabetes Trial) found no effect of intensive glucose control on major cardiovascular events (13, 14), ACCORD (Action to Control Cardiovascular Disease in Diabetes) identified an increased risk for death from cardiovascular causes and total mortality associated with intensive glucose control (12). On the basis of these results, a recent article by Montori and colleagues suggested that additional research is needed to confirm or refute the importance of tight glucose control (15). Thus, recommendations for health care providers regarding optimal hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes remain unclear. Because of the early termination of ACCORD and fewer events than anticipated in ADVANCE and VADT, there is real concern that these studies were underpowered to capture the true effects of intensive glucose control on CVD risk (1214). Therefore, we conducted a meta-analysis of randomized, controlled trials to examine the effects of intensive glucose control on CVD among patients with type 2 diabetes. Furthermore, we examined the separate effects of intensive glucose control on all-cause mortality, CVD mortality, CHD, congestive heart failure (CHF), stroke, and peripheral artery disease. In an effort to explain incongruities among trial results, we conducted subgroup analyses and examined the occurrence of severe hypoglycemia. Methods Data Sources and Searches We developed and followed a standard protocol for all steps of the review. Investigators searched the MEDLINE database (January 1950 through April 2009) using the Medical Subject Headings cardiovascular diseases; coronary disease; stroke; peripheral vascular diseases; hypoglycemic agents; and diabetes mellitus, type 2, as well as the keywords coronary heart disease, glucose control, and glycemic control. We restricted the search to randomized, controlled trials conducted among human adults (age 19 years), with no language restrictions. We also manually searched references cited in the published original reports and contacted experts in the field. Study Selection Two investigators independently reviewed the contents of 341 abstracts or full-text manuscripts identified through the literature search to determine whether they met the eligibility criteria. Studies were eligible for inclusion if 1) the study was a randomized, controlled trial; 2) the study compared intensive glucose control with conventional treatment, with a priori specification of glycemic goals for the intensive and conventional glucose control groups; 3) clinical CVD was the primary end point; 4) the study sample size was 500 patients or more; and 5) the study participants had type 2 diabetes mellitus. Reviewers resolved disagreements about study inclusion or exclusion by consensus and by referring to the original reports. Data Extraction and Quality Assessment Study investigators independently abstracted data in duplicate using a standardized data collection form. Reviewers did not contact authors to request additional information. Reviewers abstracted characteristics of each trial and its participants. Reviewers critically appraised methodological characteristics of trials, such as randomization procedures, blinded assessment of outcomes, adjudication procedures for outcomes, and follow-up rates, but did not use a scoring system to formally rate study quality of the individual trials (Appendix Table 1). Appendix Table 1. Assessment of Methodological Characteristics Reviewers recorded the following as the main outcomes of interest: number of clinical CVD, CHD, stroke, and CHF events, along with cardiovascular deaths and all-cause mortality, for the intensive and conventional glucose control groups. Reviewers also recorded single end points, including nonfatal myocardial infarction, fatal myocardial infarction, nonfatal stroke, fatal stroke, and peripheral artery disease. In addition, reviewers recorded the number of severe hypoglycemic events for each trial group. Because definitions of certain composite outcomes varied between trials, each outcome is defined for each trial in Appendix Table 2. Appendix Table 2. Definitions of Composite Outcomes for Each Trial Data Synthesis and Analysis We examined the relationship between intensive glucose control and risk for all study outcomes using relative risk and risk difference measures. We calculated the relative risks in each trial on the basis of the number of events in the intensive glucose control and conventional treatment groups and used these estimates for pooling analyses. To estimate the risk difference, we first calculated the annual absolute risk for an event in participants in each trial group by dividing the number of events in each trial group by the corresponding number of person-years (estimated as median treatment time number of participants in the trial group). We then multiplied the annual absolute risk by 5 to estimate the 5-year risk among participants in each trial group. We calculated the risk difference for each trial by subtracting the 5-year risk in the conventional glucose control group from the 5-year risk in the intensive glucose control group. We logarithmically transformed the relative risks and risk differences and their corresponding standard errors to stabilize the variance and normalize their distribution. We pooled relative risks and risk differences using both fixed-effects and DerSimonian and Laird random-effects models (16). We used inverse variance weighting to calculate fixed- and random-effects summary estimates. We assessed heterogeneity formally by using the Dersimonian and Laird Q test, considering any P value less than 0.100 as evidence of heterogeneity, and by examining the I 2 quantity. Although fixed- and random-effects models yielded similar findings, we detected between-study heterogeneity for several study outcomes (severe hypoglycemia, cardiovascular deaths, all-cause mortality, and fatal myocardial infarction). Because of this heterogeneity and trial differences in median diabetes duration of participants, achieved HbA1c levels, and therapeutic regimens, we present results from the random-effects models. We conducted a prestated subgroup analysis to examine the effects of intensive glucose control on all study outcomes. We then compared the relative risks for CVD, CHD, CHF, stroke, cardiovascular deaths, all-cause mortality, and severe hypoglycemia, as well as fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, and peripheral artery disease between the early UKPDS trials (8, 11) and the 3 more recent ACCORD, ADVANCE, and VADT trials (1214). We conducted all analyses by using Stata software, version 9.2 (Stata Corp, College Station, Texas). Role of the Funding Source This study was funded in part by a career development award from the National Heart, Lung, and Blood Institute and by an award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The funding sources played no role in the study design; collection, analysis, and interpretation of the data; writing of the report; or decision to submit the paper for publication. Results Figure 1 depicts the study selection process. We excluded 2 trials, the Kumamoto Study (n = 110) and the Veterans Affairs (VA) Diabetes Feasibility Trial (n = 153), because of small sample sizes (9, 17). The VA Diabetes Feasibility Trial was a pilot study that examined whether intensive glucose control could be effectively sustained in patients with type 2 diabetes and was a precursor to the subsequent VADT. The Kumamoto Study examined the effects of intensive glucose control on microvascular complications of diabetes. The current meta-analysis included a total of 5 trials conducted among 27 802 participants (8, 1114). Table 1 presents the characteristics of the 5 randomized, controlled trials and trial participants. The number of trial participants ranged from 753 to 11 140, while intervention duration ranged from 3.4 to 10.7 years. The UKPDS 33 and 34 recruited participants with newly diagnosed diabetes. Those inclusion criteria differed from those of ADVANCE, ACCORD and VADT, whose participants had an average duration of diabetes ranging

Effects of Low-Carbohydrate Diets Versus Low-Fat Diets on Metabolic Risk Factors: A Meta-Analysis of Randomized Controlled Clinical Trials

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.

Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial

IMPORTANCE Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. RESULTS Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01840072.

Premature deaths attributable to blood pressure in China: a prospective cohort study

BACKGROUND Hypertension is a major global-health challenge because of its high prevalence and concomitant risks of cardiovascular disease. We estimated premature deaths attributable to increased blood pressure in China. METHODS We did a prospective cohort study in a nationally representative sample of 169,871 Chinese adults aged 40 years and older. Blood pressure and other risk factors were measured at a baseline examination in 1991 and follow-up assessment was done in 1999-2000. Premature death was defined as mortality before age 72 years in men and 75 years in women, which were the average life expectancies in China in 2005. We calculated the numbers of total and premature deaths attributable to blood pressure using population-attributable risk, mortality, and the population size of China in 2005. FINDINGS Hypertension and prehypertension were significantly associated with increased all-cause and cardiovascular mortality (p<0.0001). We estimated that in 2005, 2.33 million (95% CI 2.21-2.45) cardiovascular deaths were attributable to increased blood pressure in China: 2.11 million (2.03-2.20) in adults with hypertension and 0.22 million (0.19-0.25) in adults with prehypertension. Additionally, 1.27 million (1.18-1.36) premature cardiovascular deaths were attributable to raised blood pressure in China: 1.15 million (1.08-1.22) in adults with hypertension and 0.12 million (0.10-0.14) in adults with prehypertension. Most blood pressure-related deaths were caused by cerebrovascular diseases: 1.86 million (1.76-1.96) total deaths and 1.08 million (1.00-1.15) premature deaths. INTERPRETATION Increased blood pressure is the leading preventable risk factor for premature mortality in the Chinese general population. Prevention and control of this condition should receive top public-health priority in China. FUNDING American Heart Association (USA); National Heart, Lung, and Blood Institute, National Institutes of Health (USA); Ministry of Health (China); and Ministry of Science and Technology (China).

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 Collaborations 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 -8.0mg/dL (95% CI, -11.4 to -4.6). CONCLUSION These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol.

Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis.

CONTEXT 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. OBJECTIVE 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. RESULTS 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. CONCLUSIONS 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.

Fibroblast Growth Factor 23 and Inflammation in CKD

BACKGROUND AND OBJECTIVES Levels of fibroblast growth factor 23 (FGF23) and inflammatory markers are commonly elevated in CKD, and each is associated with adverse clinical outcomes. This study tested the hypothesis that FGF23 is independently associated with inflammation in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-α, and fibrinogen was assessed in a cross-sectional analysis of 3879 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study between June 2003 and September 2008. RESULTS FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-α (r=0.4), and fibrinogen (r=0.3; P<0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (ln) transformed FGF23 was significantly associated with lnIL-6, lnCRP, lnTNF-α, and fibrinogen (P<0.001 for each). Each unit higher lnFGF23 was associated with severe inflammation, defined as levels of all inflammatory markers in the highest 25th percentile, in univariate (odds ratio [OR], 2.4 [95% confidence interval (CI), 2.0-2.9]) and multivariable-adjusted (OR, 2.0 [95% CI, 1.6-2.5]) logistic regression analyses. Ascending FGF23 quartiles were independently associated with severe inflammation (OR, 5.6 for the highest versus lowest FGF23 quartile [95% CI, 2.3-13.9]; P for trend < 0.001). CONCLUSIONS Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD.

Gender Difference in Blood Pressure Responses to Dietary Sodium Intervention in the GenSalt Study

Objective To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions. Methods We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3 mmol sodium/day), a 7-day high-salt intervention (307.8 mmol sodium/day), and a 7-day high-salt and potassium-supplementation (60 mmol potassium/day) intervention among 1906 study participants in rural China. The BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Results The BP responses to low-sodium intervention were significantly greater in women than in 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 than in men: 6.4 (5.9–6.8) versus 5.2 (4.8–5.7) mmHg for systolic and 3.1 (2.7–3.5) versus 1.7 (1.4–2.1) mmHg for diastolic (all P < 0.001). In addition, systolic BP responses to sodium interventions increased with age, and both systolic and diastolic BP responses to sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels. Conclusion These results suggest that female gender, older age, and hypertension increase the sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.