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Objective- Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA 2 -IIA (group IIA secretory phospholipase A 2 ) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA 2 -IIA in secondary prevention, we prospectively evaluated sPLA 2 -IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results- The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA 2 -IIA mass was measured (N=11 269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA 2 -IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA 2 -IIA mass (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/mL) was associated with increased risk of CVD: risk factor-adjusted hazard ratio (95% CI; P) per SD increment: 1.22 (1.08-1.38; P=0.002). This remained significant (1.18; 1.04-1.35; P=0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA 2 -IIA) had the strongest effect on sPLA 2 -II: median (25th-75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97-4.01) and 7.38 (5.38-10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89-1.38; P=0.34). Conclusions- In the JUPITER population recruited on chronic inflammation, sPLA 2 -IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA 2 -IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.

Background: Unhealthy lifestyles and inflammation contribute to cardiovascular disease (CVD). GlycA is a novel biomarker of systemic inflammation representing post-translational glycosylation of acute phase reactants and associated with increased clinical CVD risk., Hypothesis: We hypothesized that ideal cardiovascular health (CVH), as assessed by (higher) Life's Simple 7 (LS7) scores, would be associated with lower GlycA levels among individuals free of CVD in a multiethnic community-based population., Methods: This was a cross-sectional study of 6479 Multi-Ethnic Study of Atherosclerosis participants [53% women; mean age 62 ± 10 years] with GlycA levels measured at baseline by nuclear magnetic resonance spectroscopy. The LS7 metrics (smoking, physical activity, diet, body mass index, blood pressure, cholesterol, and glucose) were each scored as ideal (2), moderate (1), or poor (0). Total scores were summed and categorized as optimal (12-14), average (8-11), and inadequate (0-7). Linear regression assessed percent difference in GlycA by LS7 scores, after adjusting for age, sex, ethnicity, education, income, family history of CVD, and other inflammatory biomarkers., Results: GlycA levels were 403.4 ± 63.1, 374.4 ± 59.2, and 350.3 ± 56.2 micromoles per liter (μmol/L) for inadequate, average, and optimal CVH, respectively (P-trend <0.001). After multivariable adjustment, GlycA remained independently and inversely associated with CVH categories, with a lower mean GlycA level of 5 μmol/L (95% confidence interval 4.5-5.8) for each one unit increment in LS7 score., Conclusions: Among this group of ethnically diverse individuals without CVD, suboptimal CVH is associated with higher GlycA levels, independent of traditional inflammatory biomarkers. Strategies aimed at improving CVH might reduce GlycA, which could be a marker of reduced risk of future CVD events., (© 2018 Wiley Periodicals, Inc.)

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.