Suma Vupputuri

Passive Smoking and the Risk of Coronary Heart Disease — A Meta-Analysis of Epidemiologic Studies

BACKGROUND The effect of passive smoking on the risk of coronary heart disease is controversial. We conducted a meta-analysis of the risk of coronary heart disease associated with passive smoking among nonsmokers. METHODS We searched the Medline and Dissertation Abstracts Online data bases and reviewed citations in relevant articles to identify 18 epidemiologic (10 cohort and 8 case-control) studies that met prestated inclusion criteria. Information on the designs of the studies, the characteristics of the study subjects, exposure and outcome measures, control for potential confounding factors, and risk estimates was abstracted independently by three investigators using a standardized protocol. RESULTS Overall, nonsmokers exposed to environmental smoke had a relative risk of coronary heart disease of 1.25 (95 percent confidence interval, 1.17 to 1.32) as compared with nonsmokers not exposed to smoke. Passive smoking was consistently associated with an increased relative risk of coronary heart disease in cohort studies (relative risk, 1.21; 95 percent confidence interval, 1.14 to 1.30), in case-control studies (relative risk, 1.51; 95 percent confidence interval, 1.26 to 1.81), in men (relative risk, 1.22; 95 percent confidence interval, 1.10 to 1.35), in women (relative risk, 1.24; 95 percent confidence interval, 1.15 to 1.34), and in those exposed to smoking at home (relative risk, 1.17; 95 percent confidence interval, 1.11 to 1.24) or in the workplace (relative risk, 1.11; 95 percent confidence interval, 1.00 to 1.23). A significant dose-response relation was identified, with respective relative risks of 1.23 and 1.31 for nonsmokers who were exposed to the smoke of 1 to 19 cigarettes per day and those who were exposed to the smoke of 20 or more cigarettes per day, as compared with nonsmokers not exposed to smoke (P=0.006 for linear trend). CONCLUSIONS Passive smoking is associated with a small increase in the risk of coronary heart disease. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease may be important.

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%

Dietary Intake of Folate and Risk of Stroke in US Men and Women NHANES I Epidemiologic Follow-Up Study

Background and Purpose— Few population-based studies have examined the relationship between dietary intake of folate and risk of stroke and cardiovascular disease (CVD). This study examines the association between dietary intake of folate and the subsequent risk of stroke and CVD. Methods— Study participants included 9764 US men and women aged 25 to 74 years who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was assessed at baseline using a 24-hour dietary recall and calculated using ESHA software. Incidence data for stroke and CVD were obtained from medical records and death certificates. Results— Over an average of 19 years of follow-up, 926 incident stroke events and 3758 incident CVD events were documented. The relative risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99, P =0.03 for trend) for incident stroke events and 0.86 (95% CI: 0.78 to 0.95, P <0.001 for trend) for incident CVD events in the highest quartile of dietary folate intake (median, 405.0 &mgr;g/day) compared with those in the lowest quartile (median, 99.0 &mgr;g/day), after adjustment for established cardiovascular risk factors and dietary factors. Conclusions— Our findings indicate an inverse relationship between dietary intake of folate and subsequent risk of stroke and CVD. Increasing dietary intake of folate from food sources may be an important approach to the prevention of CVD in the US population.

Blood Lead Level Is Associated With Elevated Blood Pressure in Blacks

Abstract—Chronic lead exposure has been associated with elevated blood pressure in epidemiological studies. It is not known whether the previously observed relation between blood lead and hypertension persists after significant reductions have been made in environmental lead contamination. We examined the relation between blood lead levels and blood pressure in a representative sample of 14 952 whites and blacks aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Blood lead was measured by atomic absorption spectrophotometry and blood pressure by standard sphygmomanometry. Mean blood lead levels were significantly higher for black men and women (5.4 and 3.4 &mgr;g/dL, respectively) compared with white men and women (4.4 and 3.0 &mgr;g/dL, respectively). After multivariate adjustment for important covariables, each standard deviation higher blood lead (3.3 &mgr;g/dL) was associated with a 0.82 (95% confidence interval [CI], 0.19 to 1.44) mm Hg and a 1.55 (95% CI, 0.47 to 2.64) mm Hg higher systolic blood pressure among black men and women, respectively. In contrast, blood lead level was not associated with blood pressure among white men or women. The multivariate-adjusted odds ratio (95% CI) of hypertension associated with a 1-SD higher level of blood lead was 1.08 (95% CI, 0.99 to 1.19) for black men and 1.39 (95% CI, 1.21 to 1.61) for black women. These findings suggest that increased levels of blood lead remain an important environmental risk factor for elevated blood pressure in blacks.

Dietary potassium intake and risk of stroke in US men and women: National Health and Nutrition Examination Survey I epidemiologic follow-up study.

Background and Purpose— The few prospective studies that have explored the association between dietary intake of potassium and risk of stroke have reported inconsistent findings. This study examines the relationship between dietary potassium intake and the risk of stroke in a representative sample of the US general population. Methods— Study participants included 9805 US men and women who participated in the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-Up Study. Dietary potassium and total energy intake were estimated at baseline by using a 24-hour dietary recall. Incidence data for stroke and coronary heart disease were obtained from medical records and death certificates. Results— Over an average of 19 years of follow up, 927 stroke events and 1847 coronary heart disease events were documented. Overall, stroke hazard was significantly different among quartiles of potassium intake (likelihood ratio P =0.03); however, a test of linear trend across quartiles did not reach a customary level of statistical significance (P =0.14). Participants consuming a low potassium diet at baseline (<34.6 mmol potassium per day) experienced a 28% higher hazard of stroke (hazard ratio 1.28, 95% CI 1.11 to 1.47;P <0.001) than other participants, after adjustment for established cardiovascular disease risk factors. Conclusions— These findings suggest that low dietary potassium intake is associated with an increased risk of stroke. However, the possibility that the association is due to residual confounding cannot be entirely ruled out in this observational study.

The Cardiovascular Research Network: A New Paradigm for Cardiovascular Quality and Outcomes Research

Background—A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes. Methods and Results—The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of ≈11 million individuals treated through various health care delivery models. Each site’s rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators. Conclusions—The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.

Sugary Soda Consumption and Albuminuria: Results from the National Health and Nutrition Examination Survey, 1999–2004

BACKGROUND End-stage renal disease rates rose following widespread introduction of high fructose corn syrup in the American diet, supporting speculation that fructose harms the kidney. Sugar-sweetened soda is a primary source of fructose. We therefore hypothesized that sugary soda consumption was associated with albuminuria, a sensitive marker for kidney disease. METHODOLOGY/PRINCIPAL FINDINGS Design was a cross-sectional analysis. Data were drawn from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The setting was a representative United States population sample. Participants included adults 20 years and older with no history of diabetes mellitus (n = 12,601); after exclusions for missing outcome and covariate information (n = 3,243), the analysis dataset consisted of 9,358 subjects. Exposure was consumption of two or more sugary soft drinks, based on 24-hour dietary recall. The main outcome measure was Albuminuria, defined by albumin to creatinine ratio cutpoints of >17 mg/g (males) and >25 mg/g (females). Logistic regression adjusted for confounders (diet soda, age, race-ethnicity, gender, poverty). Interactions between age, race-ethnicity, gender, and overweight-obesity were explored. Further analysis adjusted for potential mediators: energy intake, basal metabolic rate, obesity, hypertension, lipids, serum uric acid, smoking, energy expenditure, and glycohemoglobin. Alternative soda intake definitions and cola consumption were employed. RESULTS Weighted albuminuria prevalence was 11%, and 17% consumed 2+ sugary soft drinks/day. The confounder-adjusted odds ratio for sugary soda was 1.40 (95% confidence interval: 1.13, 1.74). Associations were modified by gender (p = 0.008) and overweight-obesity (p = 0.014). Among women, the OR was 1.86 (95% CI: 1.37, 2.53); the OR among males was not significant. In the group with body mass under 25 kg/m(2), OR = 2.15 (95% confidence interval: 1.42, 3.25). Adjustment for potential mediators and use of alternative definitions of albuminuria and soda consumption did not appreciably change results. Diet sodas were not associated with albuminuria. CONCLUSIONS Findings suggest that sugary soda consumption may be associated with kidney damage, although moderate consumption of 1 or fewer sodas does not appear to be harmful. Additional studies are needed to assess whether HFCS itself, overall excess intake of sugar, or unmeasured lifestyle and confounding factors are responsible.

Construction of a Multisite DataLink Using Electronic Health Records for the Identification, Surveillance, Prevention, and Management of Diabetes Mellitus: The SUPREME-DM Project

Introduction Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. Methods We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. Results The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. Conclusion The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

Effect of Blood Pressure on Early Decline in Kidney Function Among Hypertensive Men

Abstract—Few cohort studies have examined the longitudinal association between change in blood pressure and decline in kidney function among treated hypertensive patients without chronic kidney disease. We conducted a nonconcurrent cohort study to examine the effects of blood pressure on estimated glomerular filtration rate and early kidney function decline (rise in serum creatinine ≥0.6 mg/dL during follow-up) among 504 African-American and 218 white hypertensive patients. Our results showed that each standard deviation higher treated systolic (18 mm Hg) and diastolic (10 mm Hg) blood pressure was associated with an average annual decline (95% confidence interval [CI]) in estimated glomerular filtration rate of −0.92 ([−1.49 to −0.36]P =0.001) and −0.83 ([−1.38 to −0.28]P =0.003) mL · min−1 · 1.73 m−2, respectively, after adjustment for race, age, education, income, use of antihypertensive drugs, body mass index, and history of diabetes and dyslipidemia. Likewise, each standard deviation higher systolic and diastolic blood pressure was associated with relative risks (95% CIs) of 1.81 ([1.29 to 2.55]P <0.001) and 1.55 ([1.08 to 2.22]P =0.046), respectively, for early kidney function decline. Compared with patients with a blood pressure level <140/90 mm Hg, those with a blood pressure level ≥160/95 mm Hg had a −2.67 ([−4.01 to −1.32]P <0.001) mL · min−1 · 1.73 m−2 greater annual decline in estimated glomerular filtration rate and a 5.21-fold ([2.06 to 13.21]P <0.001) greater risk of early kidney function decline. Our study found that higher levels of treated blood pressure were positively and significantly related to early decline in kidney function among hypertensive men. These results indicate that better blood pressure control might prevent the onset of chronic kidney disease among hypertensives.

Differential Estimation of CKD Using Creatinine- Versus Cystatin C–Based Estimating Equations by Category of Body Mass Index

BACKGROUND Adiposity is associated with cystatin C. Cystatin C-based glomerular filtration rate (GFR) equations may result in overestimation of chronic kidney disease (CKD) prevalence at greater body mass index (BMI) levels. STUDY DESIGN Cross-sectional. SETTING & PARTICIPANTS 6,709 US adult Third National Health and Nutrition Examination Survey participants. FACTOR BMI. OUTCOME Absolute percentage of difference in prevalence of stage 3 or 4 CKD between creatinine- and cystatin C-based estimating equations by level of BMI. MEASUREMENTS Normal weight, overweight, and obesity were defined as BMI of 18.5 to less than 25.0, 25 to less than 30.0, and 30 kg/m(2) or greater, respectively. Stage 3 or 4 CKD (estimated glomerular filtration rate [eGFR], 15 to 59 mL/min/1.73 m(2)) was defined using the 4-variable creatinine-based Modification of Diet in Renal Disease Study equation (eGFR(MDRD)); cystatin C level, age, sex, and race equation (eGFR(CysC,age,sex,race)); cystatin C-only equation (eGFR(CysC)); cystatin C level of 1.12 mg/L or greater (increased cystatin C); and an equation incorporating serum creatinine level, cystatin C level, age, sex, and race (eGFR(Cr,CysC,age,sex,race)). RESULTS Differences in stage 3 or 4 CKD prevalence estimates between eGFR(CysC,age,sex,race), eGFR(CysC), and increased cystatin C, separately, and eGFR(MDRD) were greater at higher BMI levels. Specifically, compared with estimates derived using eGFR(MDRD) for normal-weight, overweight, and obese participants, estimated prevalences of stage 3 or 4 CKD were 2.1%, 3.0%, and 6.5% greater when estimated by using eGFR(CysC,age,sex,race) (P trend = 0.005); 0.1%, 0.6%, and 2.2% greater for eGFR(CysC) (P trend = 0.03); 2.9%, 5.2%, and 9.5% greater for increased cystatin C (P trend < 0.001); and -0.1%, -0.4%, and 0.0% greater for eGFR(Cr,CysC,age,sex,race), respectively (P trend = 0.7). LIMITATIONS No gold-standard measure of GFR was available. CONCLUSIONS BMI may influence the estimated prevalence of stage 3 or 4 CKD when cystatin C-based equations are used.