PFC concentrations were available for 2,094 participants of the original subsample of 2,368 people. PFOS levels were an order of magnitude higher than the other PFCs, with a median of 19.9 μg/L serum compared with 3.8 μg/L for PFOA. Similar to results in the same data set reported by Calafat et al. (2007)
, concentrations were higher in males compared with females, non-Hispanic whites compared with Mexican Americans and non-Hispanic blacks, and people of higher SES compared with those of lower SES. There were no striking concentration differences by age. The four PFCs were log-normally distributed and were moderately correlated with one another. PFOA and PFOS were most strongly correlated, with a Spearman correlation coefficient of 0.65; PFHxS and PFNA were the least correlated at 0.12. Cholesterol, body weight, and insulin resistance outcomes varied with age, sex, and race/ethnicity and were correlated with one another in predictable ways.
The number of participants in each analysis depended on the outcome and missing data. We present results for the cholesterol analyses among adults (20–80 years of age) in and and . Supplemental Material, Figure 1 (doi:10.1289/ehp.0901165.S1), illustrates how we arrived at our final sample size, which does not include 12- to 19-year-olds (n = 640). Of adults with PFC and cholesterol measures (n = 1,310), we excluded the 20% who reported using cholesterol-lowering medications and the 3% who were missing this variable. None of the covariates were missing in > 9% of people. shows the distribution of outcomes and PFC concentrations in this subpopulation, including PFC range and number of people in each quartile. In all cases, the PFC range in the fourth quartile is much wider than in the other three quartiles. Supplemental Material, Table 1 (doi:10.1289/ehp.0901165.S1), provides information on the distribution of covariates.
Distribution of cholesterol outcomes and PFC concentrations, persons 20–80 years of age.
Change in cholesterol measure (milligrams per deciliter) per microgram per liter increase in PFC, persons 20–80 years of age.
Figure 1 Differences in cholesterol levels, persons 20–80 years of age, with increasing quartile of PFC exposure. (A) Change in TC (n = 860), (B) change in HDL (n = 860), (C) change in non-HDL (n = 860), and (D) change in LDL (n = 416). All models control (more ...) Cholesterol
presents the adjusted associations between the four cholesterol measures and PFC serum concentrations for adults [Supplemental Material, Table 2 (doi:10.1289/ehp.0901165.S1], presents crude associations). We omitted 12- to 19- year-olds because no data were available for two important covariates, alcohol and smoking. See Supplemental Material, Table 3, for results stratified by age (including 12- to 19-year-olds) and sex.
We found a positive association between TC and PFOS, PFOA, and PFNA concentrations (). Adults in the highest PFOS quartile had TC levels 13.4 mg/dL (95% CI, 3.8–23.0) higher than those in the lowest quartile. For PFOA, there was a 9.8‐mg/dL (95% CI, −0.2 to 19.7) increase, and for PFNA, a 13.9-mg/dL (95% CI, 1.9–25.9) increase. TC appeared to increase linearly across the quartiles of PFC exposure, particularly for PFNA (p-value for trend = 0.04). When examined in age and sex subgroups, results were similar, with associations of greater magnitude among persons 60–80 years of age. Associations were fewer and of smaller magnitude among 12- to 19-year-olds. In contrast, results for PFHxS indicated an inverse trend among adults (p-value for trend = 0.07). Those in the top PFHxS quartile had TC levels that were lower than those in the lowest quartile by −7.0 mg/dL (95% CI, −13.2 to −0.8). The same pattern held in the female age subgroups in particular.
We found fewer consistent trends in the HDL analyses. We observed differences by age and sex; results for all adults () may mask these findings in some cases [see Supplemental Material, Table 3 (doi:10.1289/ehp.0901165.S1)]. PFOA and PFOS were associated with higher HDL in adolescent girls [effect estimates for the top quartile compared with lowest of 4.3 (95% CI, 0.1 to 8.5) and 3.7 (95% CI, −0.5 to 7.9), respectively], with some evidence of the opposite in the older age group [in males 60–80 years of age, effect estimate for the top PFOA quartile compared with the lowest of −8.7 (95% CI, −16.3 to −1.1)]. No meaningful associations were observed between PFNA and PFHxS concentration and HDL.
Results for non-HDL were similar to those for TC, as would be expected, because the non-HDL fraction makes up 70–80% of TC (). The magnitude of effect increased slightly for PFNA and PFHxS. LDL results () should mirror those for non-HDL; however, the sample size for LDL analyses was half as large. We found a somewhat similar pattern for PFNA and PFHxS, but no association with PFOA and PFOS concentration.
We repeated all cholesterol models and adjusted for albumin. Results were substantively the same as those presented above (data not shown). Results were similar as well in models that considered PFC concentration as a continuous predictor (). PFOS, PFOA, and PFNA were all positively associated with TC and non-HDL (effect estimates were statistically significant for PFOS and PFOA). The opposite was seen for PFHxS, which was negatively associated with TC, non-HDL, and LDL.
In addition, we performed several sensitivity analyses that also had no qualitative effect on results from the quartile analysis: the inclusion of adults missing data on use of cholesterol-lowering medication, the inclusion of all adults (even those who reported taking medications), the exclusion of points identified as outliers in the continuous models from , and use of NHANES sampling weights.
We found fewer meaningful associations between body weight and PFC concentrations [see Supplemental Material, Table 3 (doi:10.1289/ehp.0901165.S1)]. The strongest effects were seen with PFOS among males. In males 12–19 and 20–59 years of age, BMI decreased with increasing PFOS exposure. Teenage boys in the highest PFOS quartile had BMIs that were 2.8 points (95% CI, −4.1 to −1.4) lower than those in the lowest quartile (p-value for trend = 0.004). In men 60–80 years of age, on the other hand, increasing PFOS exposure was associated with increased BMI [effect estimate for the top quartile compared with lowest of 1.6 (95% CI, 0.14–3.0)]. We did not see evidence of a relationship in the female age groups. Results for the other PFCs were less consistent, and those for WC were similar to BMI.
On the whole, we found no association between PFC concentrations and HOMA. Although there were isolated suggestive trends, such as a significant positive trend with PFNA in adult females and a negative one with PFHxS in adolescent females, effects were not consistent [see Supplemental Material, Table 3 (doi:10.1289/ehp.0901165.S1)].