Circulating lipoprotein subfractions and their association with aerobic fitness level

Kondisnivå, målt som maksimalt oksygenopptak (VO2max), er en sterk markør for hjertehelse. Basert på dette kan serum profiler fra friske individ med stor differanse i VO2max nivå brukes til å identifisere sirkulerende biomarkører som representerer tidlig risiko for hjerte- og karsykdom . Målet med denne studien vår å identifisere sirkulerende lipoprotein subfraksjoner som uttykkes forskjellige hos individer med store forskjeller i VO2max nivå. 218 individer (40-59 år) fra Helseundersøkelsen i Nord-Trøndelag (HUNT3) utførte en gullstandard VO2max-test og avga serumprøver. Individene ble utvalgt parvis med hvert par bestående av en lav VO2max person og en høy VO2max person (valgt ut fra enten top 15 eller bunn 15 av personer i den aktuelle aldersgruppen). Individene ble matchet for kjønn, alder, fysisk aktivitetsnivå og fastestatus. NMR lipidomics analyser ble utført på serumprøvene, som ga data på 105 lipoprotein subfraksjoner. Resultatene viste signifikant negativ korrelasjon mellom VO2max-nivå og flere lipoprotein subfraksjoner, inkludert både LDL og HDL subfraksjoner. Konsentrasjonsnedgangen i LDL subfraksjoner som følge av økende VO2max omfattet de største LDL subfraksjonen (LDL-1, LDL-2 og LDL-3). Spesielt triglyseridnivåene i disse subfraksjonene korrelerte negativt med VO2max nivå (LDL1-TG, LDL2-TG and LDL3-TG). I tillegg til dette var syv av HDL subfraksjonene signifikant økt i individer med lav VO2max, hvor av fire av syv var fra HDL-3 gruppen og to av syv var fra HDL-2 gruppen. Videre var også konsentrasjonen av 12 VLDL subfraksjoner, da spesielt de store subfraksjonen, signifikant høyerei individer med lav VO2max. Interessant nok er lipoprotein profilen til de med lav VO2max veldig lik på lipoprotein profilen sett hos individer med insulinresistens. Dette kan indikere at denne økte risikoen for hjerte- og karsykdom man har hos dem med lav VO2max og de med insulin resistens kan skyldes samme endring i lipidprofil. Konklusjonen er at vi fant signifikante forskjeller i flere lipoprotein subfraksjoner når vi sammenlignet individer med store forskjeller i VO2max. Lipoprotein profilen til individer med lav VO2max ligner den profilen vi ser hos individer med insulinresistens. Flere studier er nødvendige for å teste om noen av disse lipoprotein subfraksjonene kan utgjøre viktige risikomarkører for hjerte- og karsykdom

Lipoprotein subfraction profiling in the search of new risk markers for myocardial infarction: The HUNT study.

BackgroundTraditional biomarkers used to measure risk of myocardial infarction (MI) only explain a modest proportion of the incidence. Lipoprotein subfractions have the potential to improve risk prediction of MI.AimWe aimed to identify lipoprotein subfractions that were associated with imminent MI risk.MethodsWe identified apparently healthy participants with a predicted low 10-year risk of MI from The Trøndelag Health Survey 3 (HUNT3) that developed MI within 5 years after inclusion (cases, n = 50) and 100 matched controls. Lipoprotein subfractions were analyzed in serum by nuclear magnetic resonance spectroscopy at time of inclusion in HUNT3. Lipoprotein subfractions were compared between cases and controls in the full population (N = 150), and in subgroups of males (n = 90) and females (n = 60). In addition, a sub analysis was performed in participants that experienced MI within two years and their matched controls (n = 56).ResultsNone of the lipoprotein subfractions were significantly associated with future MI when adjusting for multiple testing (pConclusionNone of the investigated lipoprotein subfractions were associated with future MI after adjustment for multiple testing. However, our findings suggests that HDL subfractions may be of interest in relation to risk prediction for MI, especially in males. This need to be further investigated in future studies

The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy

Background: Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment. Purpose: We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention. Methods: 56 patients with stable CAD underwent three-vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as the maximum lipid core burden index within any 4 mm length across the entire lesion (maxLCBI4mm), was defined as target segment. Lipoprotein subfractions and Lipoprotein a (Lp(a)) were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy and by standard in-hospital procedures, respectively. Penalized linear regression analyses were used to identify the best predictors of maxLCBI4mm. The uncertainty of the lasso estimates was assessed as the percentage presence of a variable in resampled datasets by bootstrapping. Results: Only modest evidence was found for an association between lipoprotein subfractions and maxLCBI4mm. The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were Lp(a) (78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (74.3 % presence). When including established cardiovascular disease (CVD) risk factors in the regression model, none of the lipoprotein subfractions were considered potential predictors of maxLCBI4mm. Conclusion: In this study, serum levels of Lp(a) and free cholesterol in the smallest HDL subfractions showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurement of lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Further and larger studies are needed to assess the potential of circulating lipoprotein subfractions as meaningful biomarkers both for lipid content in coronary atheromatous plaques and as CVD risk markers

Associations between circulating microRNAs and lipid-rich coronary plaques measured with near-infrared spectroscopy

Abstract Lipid-rich coronary atherosclerotic plaques often cause myocardial infarction (MI), and circulating biomarkers that reflect lipid content may predict risk of MI. We investigated the association between circulating microRNAs (miRs) are lipid-rich coronary plaques in 47 statin-treated patients (44 males) with stable coronary artery disease undergoing percutaneous coronary intervention. We assessed lipid content in non-culprit coronary artery lesions with near-infrared spectroscopy and selected the 4 mm segment with the highest measured lipid core burden index (maxLCBI4mm). Lipid-rich plaques were predefined as a lesion with maxLCBI4mm ≥ 324.7. We analyzed 177 circulating miRs with quantitative polymerase chain reaction in plasma samples. The associations between miRs and lipid-rich plaques were analyzed with elastic net. miR-133b was the miR most strongly associated with lipid-rich coronary plaques, with an estimated 18% increase in odds of lipid-rich plaques per unit increase in miR-133b. Assessing the uncertainty by bootstrapping, miR-133b was present in 82.6% of the resampled dataset. Inclusion of established cardiovascular risk factors did not attenuate the association. No evidence was found for an association between the other analyzed miRs and lipid-rich coronary plaques. Even though the evidence for an association was modest, miR-133b could be a potential biomarker of vulnerable coronary plaques and risk of future MI. However, the prognostic value and clinical relevance of miR-133b needs to be assessed in larger cohorts

Circulating microRNAs as predictive biomarkers of myocardial infarction: Evidence from the HUNT study.

Background and aims Several risk prediction models for coronary heart disease (CHD) are available today, however, they only explain a modest proportion of the incidence. Circulating microRNAs (miRs) have recently been associated with processes in CHD development, and may therefore represent new potential risk markers. The aim of the study was to assess the incremental value of adding circulating miRs to the Framingham Risk Score (FRS). Methods This is a case-control study with a 10-year observation period, with fatal and non-fatal myocardial infarction (MI) as endpoint. At baseline, ten candidate miRs were quantified by real-time polymerase chain reaction in serum samples from 195 healthy participants (60–79 years old). During the follow-up, 96 participants experienced either a fatal (n = 36) or a non-fatal MI (n = 60), whereas the controls (n = 99) remained healthy. By using best subset logistic regression, we identified the miRs that together with the FRS for hard CHD best predicted future MI. The model evaluation was performed by 10-fold cross-validation reporting area under curve (AUC) from the receiver operating characteristic curve (ROC). Results The best miR-based logistic regression risk-prediction model for MI consisted of a combination of miR-21-5p, miR-26a-5p, mir-29c-3p, miR-144-3p and miR-151a-5p. By adding these 5 miRs to the FRS, AUC increased from 0.66 to 0.80. In comparison, adding other important CHD risk factors (waist-hip ratio, triglycerides, glucose, creatinine) to the FRS only increased AUC from 0.66 to 0.68. Conclusions Circulating levels of miRs can add value on top of traditional risk markers in predicting future MI in healthy individuals