Higher Serum Cholesterol Levels Are Associated With Reduced Systemic Inflammation and Mortality During Tuberculosis Treatment Independent of Body Mass Index

Abstract

Background: Lipids play a central role in the pathogenesis of tuberculosis (TB). The effect of serum lipid levels on TB treatment (ATT) outcomes and their association with serum inflammatory markers have not yet been characterized.Methods: Our retrospective cohort study on drug-susceptible TB patients, at the National Taiwan University Hospital, assessed the association of baseline serum lipid levels such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) with all-cause and infection-related mortality during first 9 months of ATT and baseline inflammatory markers namely C-reactive protein (CRP), total leukocyte count (WBC), and neutrophil-lymphocyte ratio (NL ratio).Results: Among 514 patients, 129 (26.6%) died due to any-cause and 72 (14.0%) died of infection. Multivariable Cox-regression showed a lower adjusted hazard ratio (aHR) of all-cause mortality in the 3rd tertiles of HDL (aHR 0.17, 95% CI 0.07–0.44) and TC (aHR 0.30, 95% CI 0.14-0.65), and lower infection-related mortality in the 3rd tertile of HDL (aHR 0.30, 95% CI 0.14–0.65) and TC (aHR 0.30, 95% CI 0.14–0.65) compared to the 1st tertile. The 3rd tertiles of LDL and TG showed no association in multivariable analysis. Similarly, 3rd tertiles of HDL and TC had lower levels of baseline inflammatory markers such as CRP, WBC, and NL ratio using linear regression analysis. Body mass index (BMI) did not show evidence of confounding or effect modification.Conclusions: Higher baseline serum cholesterol levels were associated with lower hazards of all-cause and infection-related mortality and lower levels of inflammatory markers in TB patients. BMI did not modify or confound this association.

Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis

“…Several studies have reported an association between COVID-19 severity and low serum levels of HDL-C ( 7 , 8 ), but the magnitudes of the association between COVID-19 and total cholesterol (TC), LDL-C, and triglycerides (TG) are inconsistent. This finding is in agreement with similar observations in patients with other infections, such as HIV, dengue, and tuberculosis ( 9 , 10 ). The precise mechanism underlying the relationship between COVID-19 infection and low serum lipid levels is unclear, but the low serum lipid levels have been hypothesized to reflect an acute phase response during inflammation ( 11 ).…”

“…Although LDL-C levels appear to correlate with disease activity in other infections, such as dengue ( 49 ) and tuberculosis ( 10 ), a similar consistent correlation has not been observed with COVID-19 ( 50 ). The studies reporting low LDL-C levels attribute this finding to COVID-19-induced liver injury ( 44 ), and increased uptake by monocyte-derived macrophages in patients with COVID-19 ( 51 ).…”

“…Multiple recent studies have found that patients with various infections, such as cytomegalovirus ( 36 ), Epstein-Barr virus ( 37 ), and tuberculosis ( 38 ), had lower levels of serum lipoprotein compared to non-infected controls. Several studies have established that plasma lipid levels are inversely associated with infection-related and all-cause mortality ( 10 , 39 ), and have defined the role of lipid levels in acute infectious processes ( 40 ). In line with these reports, our meta-analysis highlights the association between COVID-19 infection and lower TC, LDL-C and HDL-C levels.…”

Diabetes-Associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

“…Low LDL and HDL were associated with granuloma necrosis and fibroplasia, leading to exacerbated lung damage in TB patients and especially those with T2D [69]. Higher serum cholesterol concentrations, on the other hand, were linked to lower concentrations of serum inflammatory markers and TB-related mortality, and this was independent of BMI [70].…”

“…Low TC Associated with an increased risk of TB disease [67] Low TC, HDL-C, LDL-C Associated with more extensive lung lesions on chest radiographs/CT scans, higher degree of smear positivity [68,69] High TC, HDL-C, LDL-C Associated with lower all-cause and infection-related mortality, reduced levels of inflammation markers [70] Mouse High TC Associated with delayed expression of adaptive immunity [77] TC, total cholesterol; VLDL-C, very-low-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; HDL, high-density lipoprotein cholesterol; STZ, streptozotocin; HFD, high fat diet.…”