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Chronic inflammation may be a risk factor for the development and progression of breast cancer, yet it is unknown which inflammatory biomarkers and pathways are especially relevant. The present study included 27,071 participants (mean age = 54.5 years) in the Women's Health Study who were free of cancer and cardiovascular disease at enrollment (1992-1995), with baseline measures of 4 inflammatory biomarkers: high-sensitivity C-reactive protein, fibrinogen, N-acetyl side-chains of acute phase proteins, and soluble intercellular adhesion molecule-1. We used Cox proportional hazards regression models to evaluate associations between baseline concentrations of biomarkers and incident breast cancer, and adjusted for baseline and time-varying factors such as age and body mass index. Self-reported invasive breast cancer was confirmed against medical records for 1,497 incident cases (90% postmenopausal). We observed different patterns of risk depending on the inflammatory biomarker. There was a significant direct association between fibrinogen and breast cancer risk (for quintile 5 vs. quintile 1, adjusted hazard ratio = 1.25, 95% confidence interval: 1.03, 1.51; P for trend = 0.01). In contrast, soluble intercellular adhesion molecule-1 was inversely associated with breast cancer (for quintile 5 vs. quintile 1, adjusted hazard ratio = 0.79, 95% confidence interval: 0.66, 0.94; P for trend = 0.02). N-acetyl side-chains of acute phase proteins and high-sensitivity C-reactive protein were not associated with breast cancer. The complex association of chronic inflammation and breast cancer may be considered when formulating anti-inflammatory cancer prevention or intervention strategies.

Background: It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant., Methods: Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models., Results: Although all 3 biomarkers were correlated ( r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk., Conclusions: Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment., (© 2016 American Association for Clinical Chemistry.)

Background: Nonfasting triglycerides are similar or superior to fasting triglycerides at predicting cardiovascular events. However, diagnostic cutpoints are based on fasting triglycerides. We examined the optimal cutpoint for increased nonfasting triglycerides., Methods: We obtained baseline nonfasting (<8 h since last meal) samples from 6391 participants in the Women's Health Study who were followed prospectively for ≤17 years. The optimal diagnostic threshold for nonfasting triglycerides, determined by logistic regression models by use of c-statistics and the Youden index (sum of sensitivity and specificity minus 1), was used to calculate hazard ratios (HRs) for incident cardiovascular events. Performance was compared to thresholds recommended by the American Heart Association (AHA) and European guidelines., Results: The optimal threshold was 175 mg/dL (1.98 mmol/L), with a c-statistic of 0.656, statistically better than the AHA cutpoint of 200 mg/dL (c-statistic 0.628). For nonfasting triglycerides above and below 175 mg/dL, after adjusting for age, hypertension, smoking, hormone use, and menopausal status, the HR for cardiovascular events was 1.88 (95% CI 1.52-2.33, P < 0.001), and for triglycerides measured at 0-4 and 4-8 h since the last meal, 2.05 (1.54- 2.74) and 1.68 (1.21-2.32), respectively. We validated performance of this optimal cutpoint by use of 10-fold cross-validation and bootstrapping of multivariable models that included standard risk factors plus total and HDL cholesterol, diabetes, body mass index, and C-reactive protein., Conclusions: In this study of middle-aged and older apparently healthy women, we identified a diagnostic threshold for nonfasting hypertriglyceridemia of 175 mg/dL (1.98 mmol/L), with the potential to more accurately identify cases than the currently recommended AHA cutpoint., (© 2015 American Association for Clinical Chemistry.)