The Relationship between Sleep-Disordered Breathing and Hypertension in a Nationally Representative Sample.

Sleep-disordered breathing (SDB), characterized by abnormal respiratory patterns or inadequate quantity of ventilation, is common in adults. A positive association between SDB and hypertension has been established, in both cross-sectional and longitudinal studies. One void in the literature concerns the role of race/ethnicity in the association between SDB and hypertension. In this context, a cross-sectional study was performed on 6,783 participants in the National Health and Nutrition Examination Survey 2005-2008. Participants were ≥age 20 and free from cardiovascular disease. The outcome of interest was hypertension, defined as ≥140 mmHg systolic blood pressure (BP), and/or ≥90 mmHg diastolic BP or antihypertensive medication use. Self-reported SDB was positively associated with hypertension, independent of confounders such as depression, diabetes, cholesterol levels, and body mass index, among others. The association persisted in subgroup analyses by gender, with a stronger association among males than females, as well as by race/ethnicity, with non-Hispanic blacks displaying the strongest association. In the multivariable-adjusted model, compared to a sleep summary score of zero (referent), the OR (95% CI) of hypertension for non-Hispanic blacks was 1.34 (0.98-1.83) for a sleep summary score of 1, 1.44 (1.06-1.97) for a score of 2 and 3.72 (1.98-7.00) for a score of >3; p-trend < 0.0001. SDB was positively associated with hypertension in a large, nationally representative sample of US adults. Along with being prevalent, SDB is also treatable. Therefore, our results are important for minority race/ethnic groups who typically experience a higher baseline for negative health outcomes.

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

BACKGROUND: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. METHODS: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. FINDINGS: The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. INTERPRETATION: Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. FUNDING: US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

No association between perfluoroalkyl chemicals and hypertension in children.

BACKGROUND: Hypertension is a leading cause of cardiovascular disease worldwide. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are perfluoroalkyl chemicals (PFCs) used in the manufacture of common consumer products and detected in the blood of the majority of Americans. Emerging biological data suggest that PFC exposure may have a role in the development of hypertension. However, the association between PFCs and hypertension has not yet been explored in humans. Therefore, we examined this association in a representative sample of US children. METHODS: A cross-sectional study was performed on 1,655 children from the National Health and Nutrition Examination Survey, 1999-2000 and 2003-2008. The main outcome of interest was hypertension, defined as age, height, and sex specific systolic and/or diastolic blood pressure level at the 95th percentile. RESULTS: We found no association between serum levels of PFOA and PFOS and hypertension in either unadjusted or multivariable-adjusted analyses controlling for age, sex, race-ethnicity, body mass index, annual household income, moderate activity, total serum cholesterol, and serum cotinine. Compared with the lowest quartile, the multivariable-adjusted odds ratio (95% confidence interval) of hypertension in the highest quartile of exposure was 0.69 (0.41-1.17) for PFOA and 0.77 (0.37-1.61) for PFOS (all P-trend values >0.30). CONCLUSION: Our findings indicate that exposure to PFOA or PFOS is not significantly associated with hypertension in children at the lower PFC exposure levels typical of the general population.

The association between PFOA, PFOS and serum lipid levels in adolescents.

INTRODUCTION: Dyslipidemia in children is associated with accelerated atherosclerosis and earlier cardiovascular disease development. Environmental exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been shown to be associated with dyslipidemia in adults. However, there are few general population studies examining this association in children or adolescents. In this context, we examined the association between serum PFOA and PFOS levels and dyslipidemia in a nationally representative sample of US adolescents. METHODS: A cross-sectional study was performed on 815 participants ⩽18 years of age from the National Health and Nutrition Examination Survey 1999-2008. The main outcome was dyslipidemia, defined as total cholesterol >170 mg/dL, low-density lipoprotein cholesterol (LDL-C) >110 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL or triglycerides >150 mg/dL. RESULTS: We found that serum PFOA and PFOS were positively associated with high total cholesterol and LDL-C, independent of age, sex, race-ethnicity, body mass index, annual household income, physical activity and serum cotinine levels. Compared to subjects in quartile 1 (referent), the multivariable-adjusted odds ratio (95% confidence interval) for high total cholesterol among children in quartile 4 was 1.16 (1.05-2.12) for PFOA and 1.53 (1.11-1.64) for PFOS. PFOA and PFOS were not significantly associated with abnormal HDL-C and triglyceride levels. DISCUSSION: Our findings indicate that serum PFOA and PFOS are significantly associated with dyslipidemia in adolescents, even at the lower "background" exposure levels of the US general population.

Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease.

BACKGROUND: Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore. METHODS: We examined data from Chinese (n=1177), Malay (n=774), and Indian (n=985) adults aged 40-80 years who participated in three independent population based studies conducted from 2004-2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders. RESULTS: The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables. CONCLUSIONS: Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.

Relationship between urinary bisphenol A levels and prediabetes among subjects free of diabetes.

Bisphenol A (BPA) is a high volume production chemical used in the manufacture of polycarbonate plastics and epoxy resins. Recent experimental studies have suggested that BPA affects glucose metabolism through diverse mechanisms including insulin resistance, pancreatic ß-cell dysfunction, adipogenesis, inflammation and oxidative stress. Prediabetes is a stage earlier in the hyperglycemia continuum associated with increased future risk of developing diabetes. Therefore, we examined the association between BPA exposure and prediabetes among subjects free of diabetes. We examined the association between urinary BPA levels and prediabetes in 3,516 subjects from the National Health and Nutritional Examination Survey 2003-2008. Urinary BPA levels were examined in tertiles. Prediabetes was defined as fasting glucose concentration 100-125 mg/dL or 2-h glucose concentration of 140-199 mg/dL or an A1C value of 5.7-6.4 %. Overall, we observed a positive association between higher levels of urinary BPA and prediabetes, independent of potential confounders including body mass index, alcohol intake, blood pressure and serum cholesterol levels. Compared to tertile 1 (referent), the multivariate-adjusted odds ratio (95 % confidence interval) of prediabetes associated with tertile 3 of BPA was 1.34 (1.03-1.73), p-trend = 0.02. In subgroup analysis, this association was stronger among women and obese subjects. Higher urinary BPA levels are found to be associated with prediabetes independent of traditional diabetes risk factors. Future prospective studies are needed to confirm or disprove this finding.

Urinary bisphenol A and obesity in U.S. children.

Childhood obesity, a major public health problem, can lead to cardiovascular disease in adulthood. Studies have implicated exposure to bisphenol A (BPA), a commonly used chemical, in the development of obesity in adults. However, literature is limited on this association in children. We examined the association between urinary BPA and obesity in children aged 6-18 years from the National Health and Nutrition Examination Survey (2003-2008). The primary exposure was urinary BPA and the outcome was obesity, defined as the ≥ 95th percentile of body mass index specific for age and sex. We found a positive association between increasing levels of urinary BPA and obesity, independent of age, sex, race/ethnicity, education, physical activity, serum cotinine, and urinary creatinine. Compared with children in the lowest quartile of BPA (<1.5 ng/mL), children in the highest quartile (>5.4 ng/mL) had a multivariable odds ratio for obesity of 2.55 (95% confidence interval (CI): 1.65, 3.95) (Ptrend < 0.01). The observed positive association was predominantly present in boys (odds ratio = 3.80, 95% CI: 2.25, 6.43) (Ptrend < 0.001) and in non-Hispanic whites (odds ratio = 5.87, 95% CI: 2.15, 16.05) (Ptrend < 0.01). In a representative sample of children, urinary BPA was associated with obesity, predominantly in non-Hispanic white boys, independent of major risk factors.

Positive association between perfluoroalkyl chemicals and hyperuricemia in children.

Hyperuricemia in children is associated with increased risk of high blood pressure, metabolic syndrome, and future cardiovascular disease. Serum perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) levels have been shown to be positively associated with hyperuricemia in adults, but the association in children remains unexplored. We therefore examined the association between serum PFOA and PFOS levels and hyperuricemia in a representative sample of US children. A cross-sectional study was performed on 1,772 participants ≤18 years of age from the National Health and Nutrition Examination Survey 1999-2000 and 2003-2008. The main outcome of interest was hyperuricemia, defined as serum uric acid levels ≥6 mg/dL. We found that serum levels of PFOA and PFOS were positively associated with hyperuricemia, independent of age, sex, race/ethnicity, body mass index, annual household income, physical activity, serum total cholesterol, and serum cotinine levels. Compared with subjects in quartile 1 (referent), subjects in quartile 4 had multivariable-adjusted odds ratios for hyperuricemia of 1.62 (95% confidence interval: 1.10, 2.37) for PFOA and 1.65 (95% confidence interval: 1.10, 2.49) for PFOS. Our findings indicate that serum perfluoroalkyl chemical levels are significantly associated with hyperuricemia in children even at the lower "background" exposure levels of the US general population.

Serum cotinine levels and prehypertension in never smokers.

Background. Few studies have shown that self-reported secondhand smoke exposure in never smokers is associated with high blood pressure. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine levels, and high blood pressure in never smokers. Methods. We examined never smokers (n = 2027) from the National Health and Nutrition Examination Survey 2005-2008. Our exposure of interest was the secondhand smoke exposure estimated by serum cotinine level and our outcome was prehypertension (n = 734), defined as a systolic blood pressure of 120-139 mmHg or diastolic blood pressure of 80-89 mmHg. Results. We found that, in never smokers, serum cotinine levels were positively associated with prehypertension. Compared to those with cotinine levels in the lowest quartile (≤0.024 ng/mL), the multivariable odds ratio (95% confidence interval) of prehypertension among those with cotinine levels in the highest quartile (≥0.224 ng/mL) was 1.45(1.00, 2.11); P trend = 0.0451. In subsequent subgroup analyses, the positive association was found to be stronger among men, non-Whites, and non-obese subjects. Conclusion. Higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with prehypertension in certain subgroups of a representative sample of the US population.

Serum cystatin C and prediabetes in non-obese US adults.

Diabetes mellitus is the leading cause of end stage renal disease. Cystatin C, a marker of early renal impairment has been shown to be associated with diabetes. However, it is not clear if cystatin C is associated with prediabetes, an early stage in the hyperglycemic continuum where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. We examined 2,033 participants from the National Health and Nutrition Examination Survey 1999-2002, aged ≥ 20 years (female 47.2 %) who were free of diabetes mellitus, chronic kidney disease and with body mass index <30 kg/m(2). Prediabetes (n = 541) was defined as a 2-h glucose concentration of 140-199 mg/dL, or a fasting glucose concentration of 110-125 mg/dL, or an A1C value of 5.7-6.4 %. Cystatin C levels were categorized into gender-specific quartiles for analysis. Elevated levels of serum cystatin C were associated with prediabetes after adjusting for potential confounders including serum total cholesterol, systolic blood pressure, body mass index and C-reactive protein. Compared to those with cystatin C in the lowest quartile, the multivariable odds ratio (95 % confidence interval) of prediabetes among those in the highest quartile was 2.08 (1.09-3.97), p for trend = 0.02. Although, this association was stronger among women and non-Hispanic whites, there was no significant interaction by sex (p = 0.1) or by race-ethnicity (p = 0.6). Our findings suggest that elevated levels of serum cystatin C are associated with prediabetes in a nationally representative sample of non-obese US adults.

Sleep-disordered breathing and retinal microvascular diameter.

BACKGROUND: Sleep-disordered breathing (SDB) is an emerging risk factor for cardiovascular disease (CVD). Microvascular dysfunction has been proposed as a potential mechanism in the pathogenesis of CVD in SDB. The retinal vasculature offers a unique opportunity to investigate the systemic effects of microvascular dysfunction as it can be viewed non-invasively and is also structurally and functionally similar to microvasculature elsewhere in the body. We therefore examined the association between SDB and retinal microvascular diameter after adjusting for major confounders. METHODS: We examined n = 476 participants from the Wisconsin Sleep Cohort Study. SDB was characterized using the apnea-hypopnea index (AHI) as <5 events/h, 5-14.9 events/h, and ≥15 events/h. Outcomes of interest included the presence of retinal arteriolar narrowing (mean retinal arteriolar diameter <141.0 um) and retinal venular widening (mean venular diameter >223.0 um). RESULTS: Higher AHI was found to be positively associated with retinal venular dilatation, independent of body mass index, hypertension, diabetes, and lipid levels. Compared to an AHI of <5 events/h (referent), the multivariable-adjusted odds ratio of retinal venular widening for an AHI of 5-14.9 events/h was 1.31 (0.75-2.28) and for an AHI of >15 events/h was 2.08 (1.03-2.16); p-trend = 0.045. In contrast, there was no association between AHI and retinal arteriolar narrowing (p-trend = 0.72). CONCLUSION: Higher AHI, a marker of SDB, was positively associated with wider retinal venules, independent of age, gender, BMI, hypertension, diabetes, and lipid levels. These data suggest that the association of SDB with cardiovascular disease may be mediated, in part, by microvasculature.

Association of serum cotinine levels and hypertension in never smokers.

Hypertension is a major public health problem. Identifying novel risk factors for hypertension, including widely prevalent environmental exposures, is therefore important. Active smoking is a well-known risk factor for hypertension and cardiovascular diseases. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine, and high blood pressure among never smokers. We examined 2889 never smokers from the National Health and Nutrition Examination Survey 2005-2008. Our exposure of interest was secondhand smoke exposure among never smokers, estimated by serum cotinine level, and our main outcome was hypertension (n=1004). We found that in never smokers, higher serum cotinine levels were positively associated with hypertension. In comparison with those with serum cotinine levels ≤ 0.025 ng/mL, the multivariable odds ratio (95% confidence interval) of hypertension among those with serum cotinine levels ≥ 0.218 ng/mL was 1.44 (1.01-2.04). In addition, higher serum cotinine was positively associated with mean change in systolic blood pressure (odds ratio [95% confidence interval], 3.24 [0.86-5.63]; P=0.0061). However, no association was present with diastolic blood pressure. In conclusion, in never smokers, higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with systolic blood pressure and hypertension independent of age, sex, ethnicity, education, alcohol drinking, body mass index, glycohemoglobin, total cholesterol, and other confounders.

Combined effect of lung function level and decline increases morbidity and mortality risks.

Lung function level and decline are each predictive of morbidity and mortality. Evaluation of the combined effect of these measurements may help further identify high-risk groups. Using Copenhagen City Heart Study longitudinal spirometry data (n = 10,457), 16-21 year risks of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease mortality, and all-cause mortality were estimated from combined effects of level and decline in forced expiratory volume in one second (FEV(1)). Risks were evaluated using Cox proportional hazards models for individuals grouped by combinations of baseline predicted FEV(1) and quartiles of slope. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using stratified analysis by gender, smoking status, and baseline age (≤45 and >45). For COPD morbidity, quartiles of increasing FEV(1) decline increased HRs (95 % CI) for individuals with FEV(1) at or above the lower limit of normal (LLN) but below 100 % predicted, reaching 5.11 (2.58-10.13) for males, 11.63 (4.75-28.46) for females, and 3.09 (0.88-10.86) for never smokers in the quartile of steepest decline. Significant increasing trends were also observed for mortality and in individuals with a baseline age ≤45. Groups with 'normal' lung function (FEV(1) at or above the LLN) but excessive declines (fourth quartile of FEV(1) slope) had significantly increased mortality risks, including never smokers and individuals with a baseline age ≤45.

Bisphenol A and Metabolic Syndrome: Results from NHANES.

Background. Bisphenol A (BPA) is detected in the urine of >95% of US adults. Recent evidence from population-based studies suggests that BPA is associated with individual components for metabolic syndrome (MetS). However, no previous study has examined the direct association between BPA and MetS. Methods. We examined 2,104 participants from the National Health and Nutrition Examination Survey 2003-2008. The main outcome was the presence of MetS (n = 741). Results. Increasing levels of urinary BPA were positively associated with MetS, independent of confounders such as age, gender, race/ethnicity, smoking, alcohol intake, physical activity, and urinary creatinine. Compared to tertile 1 (referent), the multivariable adjusted odds ratio (95% confidence interval) of MetS in tertile 3 was 1.51 (1.07-2.12); P-trend was 0.02. Conclusions. Urinary BPA levels are positively associated with MetS, in a representative sample of US adults and independent of traditional risk factors for MetS. Future, prospective studies are needed to confirm our findings.

Perfluorooctanoic acid and cardiovascular disease in US adults.

BACKGROUND: Cardiovascular disease (CVD) is a major public health problem. Identifying novel risk factors for CVD, including widely prevalent environmental exposures, is therefore important. Perfluorooctanoic acid (PFOA) is a manmade chemical used in the manufacture of common household consumer products. Biomonitoring surveys have shown that PFOA is detectable in the blood of more than 98% of the US population. Experimental animal studies suggest that an association between PFOA and CVD is plausible. However, this association in humans has not been previously examined. We therefore examined the independent relationship between serum PFOA levels and CVD outcomes in a representative sample of Americans. METHODS: We examined 1216 subjects (51.2% women) from the 1999-2003 National Health and Nutritional Examination Survey. Serum PFOA levels were examined in quartiles. The main outcomes of interest were self-reported CVD, including coronary heart disease and stroke, and objectively measured peripheral arterial disease (PAD), defined as an ankle-brachial blood pressure index of less than 0.9. RESULTS: We found that increasing serum PFOA levels are positively associated with CVD and PAD, independent of confounders such as age, sex, race/ethnicity, smoking status, body mass index, diabetes mellitus, hypertension, and serum cholesterol level. Compared with quartile 1 (reference) of PFOA level, the multivariable odds ratio (95% CI) among subjects in quartile 4 was 2.01 (1.12-3.60; P = .01 for trend) for CVD and 1.78 (1.03-3.08; P = .04 for trend) for PAD. CONCLUSION: Exposure to PFOA is associated with CVD and PAD, independent of traditional cardiovascular risk factors.