Person:

Buring, Julie

Background: Cardiovascular inflammation is a key contributor to the development of atherosclerosis and the prediction of cardiovascular events among healthy women. An emerging literature suggests biomarkers of inflammation vary by geography of residence at the state-level, and are associated with individual-level socioeconomic status. Associations between cardiovascular inflammation and state-level socioeconomic conditions have not been evaluated. The study objective is to estimate whether there are independent associations between state-level socioeconomic conditions and individual-level biomarkers of inflammation, in excess of individual-level income and clinical covariates among healthy women. Methods: The authors examined cross-sectional multilevel associations among state-level socioeconomic conditions, individual-level income, and biomarkers of inflammation among women (n = 26,029) in the Women's Health Study, a nation-wide cohort of healthy women free of cardiovascular diseases at enrollment. High sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and fibrinogen were measured between 1993 and 1996. Biomarker levels were examined among women within quartiles of state-level socioeconomic conditions and within categories of individual-level income. Results: The authors found that favorable state-level socioeconomic conditions were correlated with lower hsCRP, in excess of individual-level income (e.g. state-level real per capital gross domestic product fixed effect standardized Βeta coefficient [Std B] -0.03, 95% CI -0.05, -0.004). Individual-level income was more closely associated with sICAM-1 (Std B -0.04, 95% CI -0.06, -0.03) and fibrinogen (Std B -0.05, 95% CI -0.06, -0.03) than state-level conditions. Conclusions: We found associations between state-level socioeconomic conditions and hsCRP among healthy women. Personal household income was more closely associated with sICAM-1 and fibrinogen than state-level socioeconomic conditions. Additional research should examine these associations in other cohorts, and investigate what more-advantaged states do differently than less-advantaged states that may influence levels of cardiovascular inflammation among healthy women.

Background: Several cross-sectional, but few prospective, studies suggest that inflammation may be involved in the development of hypertension. We examined markers of inflammation—high-sensitivity C-reactive protein, interleukin-6, and soluble intercellular adhesion molecule-1—and a marker of fibrinolysis, D-dimer, for their associations with incident hypertension in the Physicians’ Health Study. Methods and Results: Baseline blood values and information on hypertension-related risk factors were collected in 1982. Incident hypertension was defined as self-reported initiation of antihypertensive treatment, systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg during follow-up. With use of a nested case-control design, 396 cases of incident hypertension and controls free of hypertension were matched 1:1 on age (mean 47.4 years) and follow-up time. In crude matched-pair analyses, the conditional relative risks of hypertension in the second through fourth versus the lowest quartiles for plasma high-sensitivity C-reactive protein were 1.27, 1.73, and 1.81 (Ptrend=0.01); for interleukin-6, 1.22, 1.02, and 1.51 (Ptrend=0.06); for soluble intercellular adhesion molecule-1, 1.00, 0.80, and 1.26 (Ptrend=0.37); and for D-dimer, 1.61, 1.81, and 1.52 (Ptrend=0.46). Multivariable adjustment attenuated the estimates. The multivariable relative risks of hypertension in the second through fourth compared to the lowest quartiles of high-sensitivity C-reactive protein were 1.24, 1.60, and 1.47 (Ptrend=0.20); for interleukin-6, 1.08, 0.92, and 1.36 (Ptrend=0.16); for soluble intercellular adhesion molecule-1, 0.89, 0.79, and 1.18 (Ptrend=0.55); and for D-dimer, 1.48, 1.68, and 1.38 (Ptrend=0.63). Conclusions: Elevated plasma inflammatory markers and D-dimer were nonsignificantly associated with a higher risk of hypertension among initially healthy men.

Background: Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N‐acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high‐sensitivity C‐reactive protein (hsCRP). Methods and Results: In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow‐up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r=0.61, P<0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both Ptrend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; Ptrend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; Ptrend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; Ptrend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; Ptrend=0.001). Conclusions: In this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD. Clinical Trial Registration URL: http//clinicaltrials.gov/. Unique identifier NCT00000479.

Context: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain. Objective: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease. Design: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by analysis of covariance for thyroid categories or thyroid stimulating hormone (TSH) quintiles on a Women’s Health Study subcohort. Setting: Outpatient. Patients or Other Participants: Randomly sampled 3914 middle-aged and older women for thyroid function analysis (TSH, free T4), of whom 3321 were not on lipid-lowering therapy. Intervention: None. Main Outcome Measure: Associations of SCH and HT with cardiometabolic markers. Results: Going from euthyroid to HT, the lipoprotein subclass profiles were indicative of insulin resistance (respective values and P for trend): larger very-low-density lipoprotein size (nm) (51.5 [95% confidence interval (CI), 51.2, 51.8] to 52.9 [51.8, 54.1], P = 0.001); higher low-density lipoprotein (LDL) particle concentration (nmol/L) [1283 (95% CI, 1267, 1299) to 1358 (1298, 1418), P = 0.004], and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid (49.2; 95% CI, 48.3, 50.2) to SCH (52.1; 95% CI, 50.1, 54.0) and HT (52.1; 95% CI, 48.6, 55.6); P for trend of 0.008. Of the other biomarkers, SCH and HT were associated with higher high-sensitivity C-reactive protein and hemoglobin A1c. For increasing TSH quintiles, results were overall similar. Conclusions: In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher cardiovascular disease risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression toward SCH and overt HT.