High‐Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory‐Related Events Versus Cardiovascular Events: The Multi‐Ethnic Study of Atherosclerosis

Abstract

BackgroundHigh-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation–related death and hospitalization, and for incident cardiovascular disease (CVD).Methods and ResultsA multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code–based noncardiovascular, noncancer chronic inflammation–related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02).ConclusionsSmall- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation–related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population.

Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2 Diabetes

“…The potential clinical utility for plasma betaine and urine sarcosine should therefore be assessed in future studies by also exploring alternative reclassification measures (45 ).…”

Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

“…As previously described (16 ), participants were contacted at 9-month intervals to identify deaths and hospitalizations, with further reference to the death certificate and the National Death Index. We adjudicated death and hospital records to classify ChrIRD, as previously described in detail (16 ). We excluded diagnoses of injury, acute organ failure, psychoses, substance abuse, and some metabolic disorders such as diabetes mellitus, similar to previous studies.…”

“…Conceptually, ChrIRD reflected fatal events or those likely to result in intensive care, which included a chronic inflammatory, oxidative stress, or infectious component as one predominant pathophysiology. Two physicians independently identified the inflammatory-related International Classification of Diseases (ICD) codes among non-CVD and noncancer disorders and classified each code independently of any others in the record, achieving substantial agreement with each other, as previously described (16 ). The following chronic and severe pathologic conditions contributed to ChrIRD: infectious diseases; endocrine, nutritional, and metabolic disease; nervous system disorders; respiratory system diseases; digestive system diseases; skin diseases; musculoskeletal and connective tissue disorders; genitourinary diseases; and blood disorders.…”

“…We classified codes one at a time; consequently, a person could be placed in CVD, cancer, and ChrIRD. A complete list of ICD codes and their frequencies of occurrence was previously pub-lished (16 ). CVD events were adjudicated by physicians on the basis of medical records.…”

Cholesterol, lipoproteins and subclinical interstitial lung disease: the MESA study

“…Candidate mechanisms by which HDL-C might attenuate subclinical lung inflammation, extracellular matrix remodelling and fibrosis include modulation of endothelial function, protection against inflammation and oxidative stress, and alterations in surfactant function. [17][18][19] ApoA-I has previously been shown to have beneficial effects in reducing lung inflammation and fibrosis in animal models, 7 and greater small and medium-size HDL particle concentrations are associated with increased non-cardiovascular, non-cancer chronic inflammation-related deaths in MESA, 20 supporting an anti-inflammatory role of small HDL particles in the lungs. There are several limitations to our study, including the potential for residual confounding, the possibility that HAA likely includes pulmonary oedema, the lack of pathological validation of HAA and the use of cardiac rather than full lung CT scans to measure HAA.…”