A large-scale observational study linking various kinds of physical exercise to lipoprotein-lipid profile

Background Being a major cardiovascular risk factor, dyslipidemia is a critical problem in public health. Recommendations in performing regular physical exercise are important to prevent dyslipidemia. Methods Based on a discovery cohort with 27,735 subjects and a replication cohort with 67,512 subjects, we evaluated the associations of regularly performing 23 exercises with 4 dyslipidemia indices measured from serum, including triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TG/HDL-C ratio. Regular exercise was defined as performing 30 min of “exercise” three times a week. “Exercise” includes leisure-time activities such as jogging, swimming, etc. Sex, age, body mass index, alcohol drinking, cigarette smoking, and education level were adjusted in all statistical analyses. Results Among the 23 exercises, only jogging was associated with a decreased level of TG (95% confidence interval [C.I.] = 5.9–14.5 mg/dL) and TG/HDL-C ratio (95% C.I. = 0.22–0.49). A total of 5 exercises were associated with an increased level of HDL-C, including jogging (95% C.I. = 2.1–3.3 mg/dL), swimming (95% C.I. = 1.6–3.3 mg/dL), dance dance revolution (95% C.I. = 1.5–3.4 mg/dL), international standard dancing (95% C.I. = 1.0–2.7 mg/dL), and cycling (95% C.I. = 0.6–1.8 mg/dL). These significant findings were further well replicated in the cohort of 67,512 subjects. Conclusion Regular jogging was not only associated with an increased level of HDL-C, but also the only one exercise associated with a decreased level of TG and TG/HDL-C ratio. Nonetheless, jogging may be difficult to engage in for subjects with limited exercise capacity. We here found that swimming, dancing, and cycling are also significantly associated with an increased level of HDL-C. People who are seeking exercise to improve their lipoprotein-lipid profiles can have other choices now.

Genetic inhibition of PCSK9, atherogenic lipoprotein concentrations, and calcific aortic valve stenosis

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition reduces plasma concentrations of low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)]. Atherogenic lipoprotein levels have been linked with calcific aortic valve stenosis (CAVS). Our objectives were to determine the association between variants in PCSK9 and lipoprotein-lipid levels, coronary artery disease (CAD) and CAVS, and to evaluate if PCSK9 could be implicated in aortic valve interstitial cells (VICs) calcification.MethodsWe built a genetic risk score weight for LDL-C levels (wGRS) using 10 independent PCSK9 single nucleotide polymorphisms and determined its association with lipoprotein-lipid levels in 9692 participants of the EPIC-Norfolk study. We investigated the association between the wGRS and CAD and CAVS in the UK Biobank, as well as the association between the PCSK9 R46L variant and CAVS in a meta-analysis of published prospective, population-based studies (Copenhagen studies, 1463 cases/101,620 controls) and unpublished studies (UK Biobank, 1350 cases/349,043 controls, Malmö Diet and Cancer study, 682 cases/5963 controls and EPIC-Norfolk study, 508 cases/20,421 controls). We evaluated PCSK9 expression and localization in explanted aortic valves by capillary Western blot and immunohistochemistry in patients with and without CAVS. Von Kossa staining was used to visualize aortic leaflet calcium deposits. PCSK9 expression under oxidative stress conditions in VICs was assessed.ResultsThe wGRS was significantly associated with lower LDL-C and apoB (p<0.001), but not with Lp(a). In the UK Biobank, the association of PCSK9 variants with CAD were positively correlated with their effects on apoB levels. CAVS was less prevalent in carriers of the PCSK9 R46L variant [odds ratio=0.71 (95% confidence interval, 0.57-0.88), p<0.001]. PCSK9 expression was elevated in the aortic valves of patients with aortic sclerosis and CAVS compared to controls. In calcified leaflets, PCSK9 co-localized with calcium deposits. PCSK9 expression was induced by oxidative stress in VICs.ConclusionGenetic inhibition of PCSK9 is associated with lifelong reductions in the levels of non-Lp(a) apoB-containing lipoproteins as well as lower odds of CAD and CAVS. PCSK9 is abundant in fibrotic and calcified aortic leaflets. Oxidative stress increases PCSK9 expression in VICs. These results provide a rationale for performing randomized clinical trials of PCSK9 inhibition in CAVS.

An NMR-based lipidomic approach to identify Parkinson's disease-stage specific lipoprotein–lipid signatures in plasma

An NMR-based lipidomic approach has been applied to provide an optimal discrimination strategy for differential diagnosis of Parkinson's and Alzheimer's diseases and for staging purposes of Parkinson's patients.