Key result
Low baseline HDL inflammatory index linked to ~53% higher CVD and mortality risk.
Why the study?
HDL cholesterol is inversely associated with cardiovascular disease and possesses in vitro anti-inflammatory properties, but whether this is protective in individuals with inflammation is unknown.
Is baseline HDL inflammatory index associated with incident cardiovascular disease and mortality in individuals with chronic inflammation?
Case-Control (n=1,034)
Double-blind
Randomized in parent JUPITER trial (1:1 to rosuvastatin 20 mg vs placebo); nested case-control matched 1:1 on age and sex using risk set sampling
Yes
Is baseline HDL inflammatory index associated with incident cardiovascular disease and mortality in individuals with chronic inflammation?
Hazard Ratio: 1.53 (95% CI 1.06–2.21)
Absolute Event Rate: 52.6% vs 48.3%
p-value: p=0.02
In individuals with chronic inflammation, an anti-inflammatory HDL function (HII 0.5-1.0) is associated with a lower risk of cardiovascular events and mortality, potentially explaining the HDL paradox.
Background High‐density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti‐inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inhibit oxidation of oxidized low‐density lipoprotein (ie, the HDL inflammatory index; HII) was measured at baseline and 12 months after random allocation to rosuvastatin or placebo in a nested case‐control study of the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Evaluating Rosuvastatin) trial. There were 517 incident cases of cardiovascular disease and all‐cause mortality compared to 517 age‐ and sex‐matched controls. Multivariable conditional logistic regression was used to examine associations of HII with events. Median baseline HII was 0.54 (interquartile range, 0.50–0.59). Twelve months of rosuvastatin decreased HII by a mean of 5.3% (95% CI, −8.9% to −1.7%; P =0.005) versus 1.3% (95% CI, −6.5% to 4.0%; P =0.63) with placebo ( P =0.22 for between‐group difference). HII had a nonlinear relationship with incident events. Compared with the reference group (HII 0.5–1.0) with the lowest event rates, participants with baseline HII ≤0.5 had significantly increased risk of cardiovascular disease/mortality (adjusted hazard ratio, 1.53; 95% CI, 1.06–2.21; P =0.02). Furthermore, there was significant ( P =0.002) interaction for HDL particle number with HII, such that having more HDL particles was associated with decreased risk only when HDL was anti‐inflammatory. Conclusions In JUPITER participants recruited on the basis of chronic inflammation, HII was associated with incident cardiovascular disease/mortality, with an optimal anti‐inflammatory HII range between 0.5 and 1.0. This nonlinear relationship of anti‐inflammatory HDL function with risk may account in part for the HDL paradox. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00239681.
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Ajala et al. (2020) conducted a case-control in Primary prevention of cardiovascular disease in individuals with chronic systemic inflammation (n=1,034). Baseline HDL inflammatory index (HII) ≤0.5 vs. Baseline HDL inflammatory index (HII) >0.5 to 1.0 (reference) was evaluated on Incident cardiovascular disease (myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, CVD death) and all-cause mortality (HR 1.53, 95% CI 1.06-2.21, p=0.02). Baseline HDL inflammatory index ≤0.5 was associated with a 53% increased risk of incident CVD and mortality compared with HII 0.5–1.0 (adjusted HR 1.53; 95% CI 1.06–2.21; P=0.02).
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