Combined Hyperlipidemia: a Lense into Systemic Inflammation's Role in Accelerated Aging

Bakgrund: Atherosclerosis is a major challenge for healthcare providers as most patients with atherosclerotic cardiovascular disease (ASCVD) are >75-years old and only few of them benefit from preventive strategies. Combined hyperlipidemias are characterized by high plasma remnant and LDL cholesterol (Rem-C and LDL-C, respectively) and triglycerides (TG).

In contrast to LDL-C, elevated Rem-C and TG promote systemic low-grade inflammation; however, whether this inflammatory state impairs healthy ageing or longevity is still not clear.

Målsättning: to understand whether combined hyperlipidemias contributes to premature ASCVD, unhealthy ageing, and a decline in longevity. Specifically, we want to: 1) to identify new phenotypes and pathological processes adversely affecting healthy ageing and longevity associated with or caused by combined hyperlipidemias, and 2) to design an innovative biological clock able to improve the evaluation and management of patients in the clinic.

Arbetsplan: In order to shorten the time from discovery to implement the findings in routine clinical care , our strategy is based on the utilization of five different cohorts/biobanks already available (ca 27000 subjects in total). The work plan is based on the following aims: 1) to understand whether Rem-C and TG promote unhealthy ageing and reduce longevity, and to identify new genetic variants; 2): to compare the biochemical and functional characteristics of lipoproteins of centenarians with those of subjects having combined dyslipidemias; 3) to create a biological clock by inclusion of genetic, epigenetic, biochemical and functional characteristics of lipoproteins, which better evaluate the risk for ASCVD and cardiometabolic disease and for unhealthy ageing; 4) to prospectively validate the new biological clock on a new cohort of patients with primary and secondary hyperlipidemia.

Betydelse: Tools that better asses the risk and helps in the treatment of ASCVD and detect an unhealthy ageing will have a great positive impact on quality of life but also in economic terms for the society.