Malnutrition-inflammation modifies the relationship of cholesterol with cardiovascular disease.

In moderate and severe CKD, the association of cholesterol with subsequent cardiovascular disease (CVD) is weak. We examined whether malnutrition or inflammation (M-I) modifies the risk relationship between cholesterol levels and CVD events in African Americans with hypertensive CKD and a GFR between 20 and 65 ml/min per 1.73 m². We stratified 990 participants by the presence or absence of M-I, defined as body mass index <23 kg/m² or C-reactive protein >10 mg/L at baseline. The primary composite outcome included cardiovascular death or first hospitalization for coronary artery disease, stroke, or congestive heart failure occurring during a median follow-up of 77 months. Baseline total cholesterol (212 ± 48 versus 212 ± 44 mg/dl) and overall incidence of the primary CVD outcome (19 versus 21%) were similar in participants with (n = 304) and without (n = 686) M-I. In adjusted analyses, the CVD composite outcome exhibited a significantly stronger relationship with total cholesterol for participants without M-I than for participants with M-I at baseline (P < 0.02). In the non-M-I group, the cholesterol-adjusted hazard ratio (HR) for CVD increased progressively across cholesterol levels: HR = 1.19 [95% CI; 0.77, 1.84] and 2.18 [1.43, 3.33] in participants with cholesterol 200 to 239 and ≥240 mg/dl, respectively (reference: cholesterol <200). In the M-I group, the corresponding HRs did not vary significantly by cholesterol level. In conclusion, the presence of M-I modifies the risk relationship between cholesterol level and CVD in African Americans with hypertensive CKD.

Associations between macronutrient intake and self-reported appetite and fasting levels of appetite hormones: results from the Optimal Macronutrient Intake Trial to Prevent Heart Disease.

The authors compared effects of macronutrients on self-reported appetite and selected fasting hormone levels. The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OMNI-Heart) (2003-2005) was a randomized, 3-period, crossover feeding trial (n = 164) comparing the effects of 3 diets, each rich in a different macronutrient. Percentages of kilocalories of carbohydrate, fat, and protein were 48, 27, and 25, respectively, for the protein-rich diet; 58, 27, and 15, for the carbohydrate-rich diet; and 48, 37, and 15 for the diet rich in unsaturated fat. Food and drink were provided for each isocaloric 6-week period. Appetite was measured by visual analog scales. Pairwise differences between diets were estimated using generalized estimating equations. Compared with the protein diet, premeal appetite was 14% higher on the carbohydrate (P = 0.01) and unsaturated-fat (P = 0.003) diets. Geometric mean leptin was 8% lower on the protein diet than on the carbohydrate diet (P = 0.003). Obestatin levels were 7% and 6% lower on the protein diet than on the carbohydrate (P = 0.02) and unsaturated-fat (P = 0.004) diets, respectively. There were no between-diet differences for ghrelin. A diet rich in protein from lean meat and vegetables reduces self-reported appetite compared with diets rich in carbohydrate and unsaturated fat and can be recommended in a weight-stable setting. The observed pattern of hormone changes does not explain the inverse association between protein intake and appetite.

Inflammation, hemostasis, and the risk of kidney function decline in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse. STUDY DESIGN: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort. SETTING & PARTICIPANTS: We used data from 14,854 middle-aged adults from 4 different US communities. PREDICTOR: Markers of inflammation and hemostasis were examined. OUTCOMES & MEASUREMENTS: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression. RESULTS: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09 to 1.44; P < 0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P < 0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P < 0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95% CI, 0.55 to 0.72; P < 0.001). No independent association was found with factor VIIc level. LIMITATIONS: Although we lacked a direct measure of kidney function, associations were robust to case definitions. CONCLUSIONS: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD.

Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study.

BACKGROUND: Parental hypertension is used to classify hypertension risk in young adults, but the long-term association of parental hypertension with blood pressure (BP) change and risk of hypertension over the adult life span has not been well studied. METHODS: We examined the association of parental hypertension with BP change and hypertension risk from young adulthood through the ninth decade of life in a longitudinal cohort of 1160 male former medical students with 54 years of follow-up. RESULTS: In mixed-effects models using 29 867 BP measurements, mean systolic and diastolic BP readings were significantly higher at baseline among participants with parental hypertension. The rate of annual increase was slightly higher for systolic (0.03 mm Hg, P= .04), but not diastolic, BP in those with parental hypertension. After adjustment for baseline systolic and diastolic BP and time-dependent covariates--body mass index, alcohol consumption, coffee drinking, physical activity, and cigarette smoking--the hazard ratio (95% confidence interval [CI]) of hypertension development was 1.5 (1.2-2.0) for men with maternal hypertension only, 1.8 (1.4-2.4) for men with paternal hypertension only, and 2.4 (1.8-3.2) for men with hypertension in both parents compared with men whose parents never developed hypertension. Early-onset (at age

The case for a population standardized infection ratio (SIR): A metric that marries the device SIR to the standardized utilization ratio (SUR).

BACKGROUND: The device standardized infection ratio (SIR) is used to compare unit and hospital performance for different publicly reported infections. Interventions to reduce unnecessary device use may select a higher-risk population, leading to a paradoxical increase in SIR for some high-performing facilities. The standardized utilization ratio (SUR) adjusts for device use for different units and facilities. METHODS: We calculated the device SIR (calculated based on actual device days) and population SIR (defined as Σ observed events divided by Σ predicted events based on predicted device days), adjusting for the facility SUR for both central-line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) in 84 hospitals from a single system for calendar years 2016 and 2017. RESULTS: The central-line SUR was 1.02 for 801,172 central-line days, with a device SIR of 0.76 and a population SIR of 0.78, a 1.6% relative increase. On the other hand, the urinary catheter SUR was 0.90 for 757,504 urinary catheter days, with a device SIR of 0.84 and a population SIR of 0.76, a 10.0% relative decrease. The cumulative attributable difference for CAUTI to a target SIR of 1 was -135.4 for the device SIR compared to -203.66 for the population SIR, a 50.8% increase in prevented events. CONCLUSION: Population SIR accounts for predicted device utilization; thus, it is an attractive metric with which to address overall risk of infection or harm to a patient population. It also reduces the risk of selection bias that may impact the device SIR with interventions to reduce device use.

A Surgeon Scorecard Is Associated with Improved Value in Elective Primary Hip and Knee Arthroplasty.

BACKGROUND: Despite increasing interest in total joint arthroplasty registries, evidence of the impact of physician-level performance on the value of care provided to patients undergoing hip and knee arthroplasty is lacking. The purpose of this study was to examine the effectiveness of an unblinded orthopaedic surgeon-specific value scorecard in improving patient outcomes and reducing hospital costs. METHODS: We retrospectively analyzed patient outcomes and hospital costs associated with total joint arthroplasties before and 9 months after the introduction of a Surgeon Value Scorecard at an urban tertiary care center. From August 2016 to May 2017, orthopaedic surgeons received an unblinded monthly Surgeon Value Scorecard summarizing a rolling 6-month view of results by surgeon for patients attributed to Diagnosis Related Group 470 (major lower-extremity arthroplasty without comorbidity or complication). Prior to implementation, surgeons were educated on the scorecard and participated in the development of a document outlining the definition and calculation of included metrics. Scorecard metrics were grouped into 5 categories: patient demographic characteristics, patient outcomes (for example, length of stay, discharge disposition, readmissions), patient experience, financial, and operational (for example, operative times). Financial (cost) measures and patient outcomes were selected as the key performance indicators analyzed in this study. Continuous variables were analyzed using the t test when a normal distribution was assumed and using Mann-Whitney tests when a non-normal distribution was assumed. Categorical variables were compared using chi-square tests. Significance was defined as p < 0.05. RESULTS: After 9 months of unblinded Surgeon Value Scorecard distribution, the mean total costs for total joint arthroplasties decreased by 8.7%, from $17,996 to $16,426 (p < 0.001). The mean total direct variable costs decreased by 17.1% from $10,945 to $9,070 (p < 0.001), and implant costs decreased by 5.3% (p < 0.001). Length of stay also decreased by 0.2 day to 1.7 days (p < 0.001), and, although there was improvement in the home-discharge rate, 30-day readmission rate, and 90-day readmission rate, the differences were not significant (p > 0.05). CONCLUSIONS: The implementation of a surgeon-specific value scorecard for lower-extremity joint arthroplasties was associated with reduced total and direct variable hospital costs, reduced implant costs, decreased variation in costs, and reduced postoperative length of stay, without compromising clinical outcomes. CLINICAL RELEVANCE: Sharing unblinded clinical and financial outcomes with surgeons may promote a culture of shared accountability and may empower surgeons to improve value-based decision-making in care delivery.

C-reactive protein and colorectal cancer risk: a systematic review of prospective studies.

C-reactive protein is a sensitive but nonspecific systemic marker of inflammation. Several prospective studies have investigated the association of prediagnostic circulating C-reactive protein concentrations with the development of colorectal cancer, but the results have been inconsistent. We performed a systematic review of prospective studies of the association between prediagnostic measurements of circulating high-sensitivity C-reactive protein and development of invasive colorectal cancer. Authors of original studies were contacted to acquire uniform data. We combined relative risks (RR) for colorectal cancer associated with a one unit change in natural logarithm-transformed high-sensitivity C-reactive protein using inverse variance weighted random effects models. We identified eight eligible studies, which included 1,159 colorectal cancer cases and 37,986 controls. The summary RR per one unit change in natural log-transformed high-sensitivity C-reactive protein was 1.12 (95% confidence intervals [CI], 1.01-1.25) for colorectal cancer, 1.13 (95% CI, 1.00-1.27) for colon cancer, and 1.06 (95% CI, 0.86-1.30) for rectal cancer. The association was stronger in men (RR, 1.18; 95% CI, 1.04-1.34) compared to women (RR, 1.09; 95% CI, 0.93-1.27) but this difference was sensitive to the findings from a single study. Prediagnostic high-sensitivity C-reactive protein concentrations were weakly associated with an increased risk for colorectal cancer. More work is needed to understand the extent to which circulating high-sensitivity C-reactive protein or other blood inflammatory markers are related to colonic inflammation.

Weight loss during the intensive intervention phase of the weight-loss maintenance trial.

BACKGROUND: To improve methods for long-term weight management, the Weight Loss Maintenance (WLM) trial, a four-center randomized trial, was conducted to compare alternative strategies for maintaining weight loss over a 30-month period. This paper describes methods and results for the initial 6-month weight-loss program (Phase I). METHODS: Eligible adults were aged > or =25, overweight or obese (BMI=25-45 kg/m2), and on medications for hypertension and/or dyslipidemia. Anthropomorphic, demographic, and psychosocial measures were collected at baseline and 6 months. Participants (n=1685) attended 20 weekly group sessions to encourage calorie restriction, moderate-intensity physical activity, and the DASH (dietary approaches to stop hypertension) dietary pattern. Weight-loss predictors with missing data were replaced by multiple imputation. RESULTS: Participants were 44% African American and 67% women; 79% were obese (BMI> or =30), 87% were taking anti-hypertensive medications, and 38% were taking antidyslipidemia medications. Participants attended an average of 72% of 20 group sessions. They self-reported 117 minutes of moderate-intensity physical activity per week, kept 3.7 daily food records per week, and consumed 2.9 servings of fruits and vegetables per day. The Phase-I follow-up rate was 92%. Mean (SD) weight change was -5.8 kg (4.4), and 69% lost at least 4 kg. All race-gender subgroups lost substantial weight: African-American men (-5.4 kg +/- 7.7); African-American women (-4.1 kg +/- 2.9); non-African-American men (-8.5 kg +/- 12.9); and non-African-American women (-5.8 kg +/- 6.1). Behavioral measures (e.g., diet records and physical activity) accounted for most of the weight-loss variation, although the association between behavioral measures and weight loss differed by race and gender groups. CONCLUSIONS: The WLM behavioral intervention successfully achieved clinically significant short-term weight loss in a diverse population of high-risk patients.

The effect of weight loss on C-reactive protein: a systematic review.

BACKGROUND: Several studies suggest that weight loss reduces C-reactive protein (CRP) level; however, the consistency and magnitude of this effect has not been well characterized. Our objective was to test the hypothesis that weight loss is directly related to a decline in CRP level. DATA SOURCES: We searched the Cochrane Controlled Trials Register and MEDLINE databases and conducted hand searches and reviews of bibliographies to identify relevant weight loss intervention studies. STUDY SELECTION: We included all weight loss intervention studies that had at least 1 arm that was a surgical, lifestyle, dietary, and/or exercise intervention. Abstracts were independently selected by 2 reviewers. DATA EXTRACTION: Two reviewers independently abstracted data on the characteristics of each study population, weight loss intervention, and change in weight and CRP level from each arm of all included studies. DATA SYNTHESIS: We analyzed the mean change in CRP level (milligrams per liter) and the mean weight change (kilograms), comparing the preintervention and postintervention values from each arm of 33 included studies using graphical displays of these data and weighted regression analyses to quantify the association. RESULTS: Weight loss was associated with a decline in CRP level. Across all studies (lifestyle and surgical interventions), we found that for each 1 kg of weight loss, the mean change in CRP level was -0.13 mg/L (weighted Pearson correlation, r = 0.85). The weighted correlation for weight and change in CRP level in the lifestyle interventions alone was 0.30 (slope, 0.06). The association appeared roughly linear. CONCLUSION: Our results suggest that weight loss may be an effective nonpharmacologic strategy for lowering CRP level.

Design and implementation of an interactive website to support long-term maintenance of weight loss.

BACKGROUND: For most individuals, long-term maintenance of weight loss requires long-term, supportive intervention. Internet-based weight loss maintenance programs offer considerable potential for meeting this need. Careful design processes are required to maximize adherence and minimize attrition. OBJECTIVE: This paper describes the development, implementation and use of a Web-based intervention program designed to help those who have recently lost weight sustain their weight loss over 1 year. METHODS: The weight loss maintenance website was developed over a 1-year period by an interdisciplinary team of public health researchers, behavior change intervention experts, applications developers, and interface designers. Key interactive features of the final site include social support, self-monitoring, written guidelines for diet and physical activity, links to appropriate websites, supportive tools for behavior change, check-in accountability, tailored reinforcement messages, and problem solving and relapse prevention training. The weight loss maintenance program included a reminder system (automated email and telephone messages) that prompted participants to return to the website if they missed their check-in date. If there was no log-in response to the email and telephone automated prompts, a staff member called the participant. We tracked the proportion of participants with at least one log-in per month, and analyzed log-ins as a result of automated prompts. RESULTS: The mean age of the 348 participants enrolled in an ongoing randomized trial and assigned to use the website was 56 years; 63% were female, and 38% were African American. While weight loss data will not be available until mid-2008, website use remained high during the first year with over 80% of the participants still using the website during month 12. During the first 52 weeks, participants averaged 35 weeks with at least one log-in. Email and telephone prompts appear to be very effective at helping participants sustain ongoing website use. CONCLUSIONS: Developing interactive websites is expensive, complex, and time consuming. We found that extensive paper prototyping well in advance of programming and a versatile product manager who could work with project staff at all levels of detail were essential to keeping the development process efficient. TRIAL REGISTRATION: clinicaltrials.gov NCT00054925.

Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial.

CONTEXT: Behavioral weight loss interventions achieve short-term success, but re-gain is common. OBJECTIVE: To compare 2 weight loss maintenance interventions with a self-directed control group. DESIGN, SETTING, AND PARTICIPANTS: Two-phase trial in which 1032 overweight or obese adults (38% African American, 63% women) with hypertension, dyslipidemia, or both who had lost at least 4 kg during a 6-month weight loss program (phase 1) were randomized to a weight-loss maintenance intervention (phase 2). Enrollment at 4 academic centers occurred August 2003-July 2004 and randomization, February-December 2004. Data collection was completed in June 2007. INTERVENTIONS: After the phase 1 weight-loss program, participants were randomized to one of the following groups for 30 months: monthly personal contact, unlimited access to an interactive technology-based intervention, or self-directed control. Main Outcome Changes in weight from randomization. RESULTS: Mean entry weight was 96.7 kg. During the initial 6-month program, mean weight loss was 8.5 kg. After randomization, weight regain occurred. Participants in the personal-contact group regained less weight (4.0 kg) than those in the self-directed group (5.5 kg; mean difference at 30 months, -1.5 kg; 95% confidence interval [CI], -2.4 to -0.6 kg; P = .001). At 30 months, weight regain did not differ between the interactive technology-based (5.2 kg) and self-directed groups (5.5 kg; mean difference -0.3 kg; 95% CI, -1.2 to 0.6 kg; P = .51); however, weight regain was lower in the interactive technology-based than in the self-directed group at 18 months (mean difference, -1.1 kg; 95% CI, -1.9 to -0.4 kg; P = .003) and at 24 months (mean difference, -0.9 kg; 95% CI, -1.7 to -0.02 kg; P = .04). At 30 months, the difference between the personal-contact and interactive technology-based group was -1.2 kg (95% CI -2.1 to -0.3; P = .008). Effects did not differ significantly by sex, race, age, and body mass index subgroups. Overall, 71% of study participants remained below entry weight. CONCLUSIONS: The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level. Monthly brief personal contact provided modest benefit in sustaining weight loss, whereas an interactive technology-based intervention provided early but transient benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054925.

Baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Clinical Trial and Cohort Study.

BACKGROUND: African Americans are at increased risk of kidney failure caused by hypertension. The primary objective of the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study is to identify risk factors for progressive kidney disease in African Americans with hypertensive chronic kidney disease in the setting of recommended antihypertensive therapy. STUDY DESIGN, SETTING, & PARTICIPANTS: On completion of the AASK Trial, a randomized, double-blind, 3 x 2 factorial trial, participants who had not yet begun dialysis treatment or undergone kidney transplantation were invited to enroll in a prospective Cohort Study. Cohort Study participants received recommended antihypertensive drug therapy, including high rates of angiotensin-converting enzyme-inhibitor (73%) and angiotensin receptor blocker (10%) use with a blood pressure goal of less than 130/80 mm Hg. PREDICTOR, OUTCOMES, & MEASUREMENTS: Baseline clinical and demographic characteristics are described separately at the baseline of the AASK Trial and Cohort Study. RESULTS: Of 1,094 persons enrolled in the AASK Trial (June 1995 to September 2001; mean age, 55 years; 61% men), 691 enrolled in the AASK Cohort Study (April 2002 to present), 299 died or reached dialysis therapy or transplantation, and 104 declined to participate in the AASK Cohort Study. Mean baseline systolic/diastolic blood pressures were 150/96 mm Hg in the Trial and 136/81 mm Hg in the Cohort Study. Cohort Study participants had greater serum creatinine levels at the start of the Cohort Study (2.3 versus 1.8 mg/dL [203 versus 159 micromol/L]), corresponding to an estimated glomerular filtration rate of 43.8 versus 50.3 mL/min/1.73 m2 (0.73 versus 0.84 mL/s/1.73 m2), than Trial participants and greater urine protein-creatinine ratios (0.38 versus 0.19 mg/mg, respectively). Individuals who were eligible, but declined to participate in the Cohort Study, had greater systolic blood pressure, but similar kidney function. LIMITATIONS: Some parameters, such as iothalamate glomerular filtration rate, urinary albumin level, echocardiogram, and ambulatory blood pressure, were not performed in both the Trial and the Cohort Study, limiting the ability to evaluate changes in these parameters over time. CONCLUSION: Despite well-controlled blood pressure in the AASK Trial, Cohort Study participants still had evidence of progressive chronic kidney disease. Thus, the AASK Cohort Study is well positioned to address its primary objective.

Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial.

BACKGROUND: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. SETTING: 4 clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent behavioral intervention that implemented long-established recommendations ("established"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet ("established plus DASH"); and advice only. MEASUREMENTS: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. RESULTS: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. LIMITATIONS: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. CONCLUSIONS: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.

Short stature and the risk of adiposity, insulin resistance, and type 2 diabetes in middle age: the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.

OBJECTIVE: To investigate the association between stature-related measurements (height, leg length, and leg length-to-height ratio) and adiposity, insulin resistance, and glucose intolerance. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of a nationally representative sample of 7,424 adults aged 40-74 years, from the Third National Health and Nutrition Examination Survey (1988-1994). The main outcome measures were percent body fat, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose intolerance based on the World Health Organization's 1985 criteria for an oral glucose tolerance test. RESULTS: Shorter height and leg length, and lower leg length-to-height ratio, were associated with higher percent body fat, especially in women. Lower leg length-to-height ratio was associated with greater insulin resistance estimated by HOMA-IR. In multinomial regression models adjusting for potential confounders, including percent body fat, the relative prevalence of type 2 diabetes per 1-SD lower values in height, leg length, and leg length-to-height ratio were 1.10 (95% CI 0.94-0.29), 1.17 (0.98-1.39), and 1.19 (1.02-1.39), respectively. CONCLUSIONS: Our study supports the hypothesis that adult markers of prepubertal growth, especially leg length-to-height ratio, are associated with adiposity, insulin resistance, and type 2 diabetes in the general U.S. population.

C-reactive protein levels and subsequent cancer outcomes: results from a prospective cohort study.

Chronic inflammation has been implicated in the pathogenesis of many common chronic diseases, including cancer. C-reactive protein (CRP) concentration is a non-specific serum marker of inflammation, and higher levels have been observed among individuals who go on to develop cardiovascular disease. Nested case-control studies were conducted within the CLUE II study, a community-based cohort, to examine the association between CRP concentrations and subsequent development of colorectal or prostate cancer. CRP concentrations were higher among individuals who went on to develop colon cancer, but not rectal or prostate cancer, compared with controls. The association between CRP concentrations and development of colon cancer is consistent with other evidence suggesting a role of inflammation and cancer. Preventive interventions that decrease systemic chronic inflammation have the potential to reduce certain types of cancer as well as cardiovascular disease. However, the potential benefits of anti-inflammatory chemopreventive agents must be weighed against their adverse effects before widespread use is recommended.

Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000.

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality and is an important marker of subclinical coronary heart disease. However, estimates of PAD prevalence in the general US population have varied widely. METHODS AND RESULTS: We analyzed data from 2174 participants aged 40 years and older from the 1999-2000 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index <0.90 in either leg. The prevalence of PAD among adults aged 40 years and over in the United States was 4.3% (95% CI 3.1% to 5.5%), which corresponds to approximately 5 million individuals (95% CI 4 to 7 million). Among those aged 70 years or over, the prevalence was 14.5% (95% CI 10.8% to 18.2%). In age- and gender-adjusted logistic regression analyses, black race/ethnicity (OR 2.83, 95% CI 1.48 to 5.42) current smoking (OR 4.46, 95% CI 2.25 to 8.84), diabetes (OR 2.71, 95% CI 1.03 to 7.12), hypertension (OR 1.75, 95% CI 0.97 to 3.13), hypercholesterolemia (OR 1.68, 95% CI 1.09 to 2.57), and low kidney function (OR 2.00, 95% CI 1.08 to 3.70) were positively associated with prevalent PAD. More than 95% of persons with PAD had 1 or more cardiovascular disease risk factors. Elevated fibrinogen and C-reactive protein levels were also associated with PAD. CONCLUSIONS: This study provides nationally representative prevalence estimates of PAD in the United States, revealing that PAD affects more than 5 million adults. PAD prevalence increases dramatically with age and disproportionately affects blacks. The vast majority of individuals with PAD have 1 or more cardiovascular disease risk factors that should be targeted for therapy.

Inflammation modifies the effects of a reduced-fat low-cholesterol diet on lipids: results from the DASH-sodium trial.

BACKGROUND: Inflammatory mediators regulate key aspects of lipid metabolism. We hypothesized that inflammation could diminish the cholesterol-lowering effect of a reduced-fat/low-cholesterol diet. METHODS AND RESULTS: After a 2-week run-in period on a control diet (37% total fat, 16% saturated fat), 100 participants were randomized to the control or DASH diet (27% total fat, 6% saturated fat) for 12 weeks. Median C-reactive protein (CRP) at baseline was 2.37 mg/L (interquartile range, 1.20, 3.79). The DASH diet, net of control, had no effect on CRP. Overall, there were significant net reductions in total (-0.34 mmol/L), LDL (-0.29 mmol/L), and HDL (-0.12 mmol/L) cholesterol from the DASH diet (each, P<0.001) and little change in triglycerides (+0.05 mmol/L, P=0.21). Baseline CRP was strongly associated with lipid responsiveness to the DASH diet. Total and LDL cholesterol were reduced to a greater degree in those with a "low" (below median) compared with a "high" (above median) baseline CRP (total, -9.8% versus -3%; P for interaction=0.006; LDL cholesterol, -11.8% versus -3%; P for interaction=0.009). Reductions in HDL cholesterol (-8.8%) were similar in persons with low versus high CRP. Triglycerides were increased in those with a high CRP but not in those with a low CRP (19.8% versus +0%; P for interaction=0.019). CONCLUSIONS: In this study, the presence of increased CRP was associated with less total and LDL cholesterol reduction and a greater increase in triglycerides from a reduced-fat/low-cholesterol diet. These findings document an additional mechanism by which inflammation might increase cardiovascular disease risk.

Smoking cessation and cardiovascular disease risk factors: results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Cigarette smoking is a major risk factor for the development and progression of cardiovascular disease. While smoking is associated with increased levels of inflammatory markers and accelerated atherosclerosis, few studies have examined the impact of smoking cessation on levels of inflammatory markers. The degree and rate at which inflammation subsides after smoking cessation are uncertain. It also remains unclear as to whether traditional risk factors can adequately explain the observed decline in cardiovascular risk following smoking cessation. METHODS AND FINDINGS: Using data from 15,489 individuals who participated in the Third National Health and Nutrition Examination Survey (NHANES III), we analyzed the association between smoking and smoking cessation on levels of inflammatory markers and traditional cardiovascular risk factors. In particular, we examined changes in C-reactive protein, white blood cell count, albumin, and fibrinogen. Inflammatory markers demonstrated a dose-dependent and temporal relationship to smoking and smoking cessation. Both inflammatory and traditional risk factors improved with decreased intensity of smoking. With increased time since smoking cessation, inflammatory markers resolved more slowly than traditional cardiovascular risk factors. CONCLUSION: Inflammatory markers may be more accurate indicators of atherosclerotic disease. Inflammatory markers returned to baseline levels 5 y after smoking cessation, consistent with the time frame associated with cardiovascular risk reduction observed in both the MONICA and Northwick Park Heart studies. Our results suggest that the inflammatory component of cardiovascular disease resulting from smoking is reversible with reduced tobacco exposure and smoking cessation.

A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: results from a randomized controlled feeding study.

BACKGROUND: Oxidation of LDL (oxLDL) is thought to have an important role in early stages of atherogenesis. Antibody to oxLDL (Ab-oxLDL) has been proposed as a biomarker which might be directly associated with oxidative stress. Yet studies designed to test this hypothesis are lacking. We tested the hypothesis that consumption of a healthy diet rich in fruits and vegetables and reduced in saturated fat, total fat, and cholesterol will concomitantly reduce oxidative stress and Ab-oxLDL. METHODS: One hundred and three healthy individuals were randomly assigned to consume a typical American (control) diet or the DASH diet rich in fruits, vegetables and low-fat dairy products and reduced in fat (27%), saturated fat (7%), and cholesterol (150 mg/day) for 3 months. Outcomes were urinary isoprostanes (in vivo marker of oxidative stress), oxygen radical absorbing capacity (ORAC, an in vitro assay measuring antioxidant activity in serum), and Ab-oxLDL measured at baseline, 1-3 months of feeding. RESULTS: Compared to the control diet, consumption of the DASH diet significantly lowered urinary isoprostane (-226 pg/ml, 95% CI: -420 to -32, P=0.023). Compared with the control group, change in ORAC was higher in the DASH group, 143 trolox units/ml (95% CI: -23 to 308, P=0.091). In comparison with the control diet, increased titers of Ab-oxLDL (37 mU/ml [95% CI: 16-57, P=0.006]) were seen after consumption of the DASH diet. Higher titers of Ab-oxLDL occurred at month 2 (56 mU/ml, 95% CI: 20-90, P=0.004) and month 3 (41 mU/ml, 95% CI: -6 to 88, P=0.082), after initially small increases at month 1 (20 mU/ml, 95% CI: -10 to 51, P=0.176). End-of-study increases in AB-oxLDL were highly correlated with increased ORAC (Spearman's rho=0.46, P<0.0001), but not with changes in specific carotenoids, tocopherols or with change in LDL cholesterol (each: P>0.10). CONCLUSION: Consumption of a healthy diet replete in antioxidants reduced oxidative stress (urinary isoprostanes) yet increased Ab-oxLDL. This indirect association of Ab-oxLDL with urinary isoprostanes hinders use of Ab-oxLDL as a marker of oxidative damage.