Abstract
BackgroundDyslipidemia is a risk factor for cardiovascular disease, with elevated low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) recognized as risk factors for acute coronary events. Studies suggest an association between low cholesterol levels and poor outcomes in acute sepsis. We sought to determine the relationship between baseline cholesterol levels and long-term rates of sepsis.MethodsWe used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based cohort of 30,239 community-dwelling adults. The primary outcome was first sepsis event, defined as hospitalization for an infection with the presence of ≥2 systemic inflammatory response syndrome criteria (abnormal temperature, heart rate, respiratory rate, white blood cell count) during the first 28 hours of hospitalization. Cox models assessed the association between quartiles of HDL-C or LDL-C and first sepsis event, adjusted for participant demographics, health behaviors, chronic medical conditions, and biomarkers.ResultsWe included 29,690 subjects with available baseline HDL-C and LDL-C. There were 3423 hospitalizations for serious infections, with 1845 total sepsis events among 1526 individuals. Serum HDL-C quartile was not associated with long-term rates of sepsis (hazard ratio (HR) (95% CI): Q1 (HDL-C 5–40 mg/dl), 1.08 (0.91–1.28); Q2 (HDL-C 41–49 mg/dl), 1.06 (0.90–1.26); Q3 (HDL-C 50–61 mg/dl), 1.04 (0.89–1.23); Q4, reference). However, compared with the highest quartile of LDL-C, low LDL-C was associated with higher rates of sepsis (Q1 (LDL-C 3–89 mg/dl), 1.30 (1.10–1.52); Q2 (LDL-C 90–111 mg/dl), 1.24 (1.06–1.47); Q3 (LDL-C 112–135 mg/dl), 1.07 (0.91–1.26); Q4, reference).ConclusionLow LDL-C was associated with higher long-terms rates of community-acquired sepsis. HDL-C level was not associated with long-term sepsis rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1579-8) contains supplementary material, which is available to authorized users.
Highlights
Dyslipidemia is a risk factor for cardiovascular disease, with elevated low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) recognized as risk factors for acute coronary events
We have demonstrated that cardiovascular disease is a risk factor for incident sepsis events [17]
Compared with the highest quartile, participants in the lowest HDL-C quartile were more likely to be male, White, have less than a high school education, reside in the stroke belt, be a current smoker, and use no alcohol. This group was more likely to have a number of chronic medical conditions and biomarker abnormalities, including coronary artery disease (CAD), diabetes, hypertension, obesity, stroke, statin use, elevated high-sensitivity C-reactive protein (hs-CRP)/cystatinC/albumin-to-creatinine ratio (ACR), and reduced estimated glomerular filtration rate (eGFR)
Summary
Dyslipidemia is a risk factor for cardiovascular disease, with elevated low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) recognized as risk factors for acute coronary events. Studies suggest an association between low cholesterol levels and poor outcomes in acute sepsis. At the forefront has been the institution of HMG-CoA reductase inhibitor (statin) drug therapy to lower low-density lipoprotein cholesterol (LDL-C) to target levels with significant benefit [1]. More controversial has been the association between lower levels of high-density lipoprotein cholesterol (HDL-C) and increased risk of CAD. The landmark Framingham study demonstrated that low HDL-C was a risk factor for CAD death in both males and females [2]. Recent studies found no additional benefit to raising serum HDL-C levels with medications in patients with optimized LDL-C already on statins [3]
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