Leisure time physical activity is associated with improved HDL functionality in high cardiovascular risk individuals: a cohort study.

AIMS Physical activity has consistently been shown to improve cardiovascular health and high-density lipoprotein-cholesterol levels. However, only small and heterogeneous studies have investigated the effect of exercise on high-density lipoprotein functions. Our aim is to evaluate, in the largest observational study to date, the association between leisure time physical activity and a range of high-density lipoprotein functional traits. METHODS The study sample consisted of 296 Spanish adults at high cardiovascular risk. Usual leisure time physical activity and eight measures of high-density lipoprotein functionality were averaged over two measurements, one year apart. Multivariable linear regression models were used to explore the association between leisure time physical activity (exposure) and each high-density lipoprotein functional trait (outcome), adjusted for cardiovascular risk factors. RESULTS Higher levels of leisure time physical activity were positively and linearly associated with average levels over one year of plasma high-density lipoprotein-cholesterol and apolipoprotein A-I, paraoxonase-1 antioxidant activity, high-density lipoprotein capacity to esterify cholesterol and cholesterol efflux capacity in individuals free of type 2 diabetes only. The increased cholesterol esterification index with increasing leisure time physical activity reached a plateau at around 300 metabolic equivalents.min/day. In individuals with diabetes, the relationship with cholesteryl ester transfer protein followed a U-shape, with a decreased cholesteryl ester transfer protein activity from 0 to 300 metabolic equivalents.min/day, but increasing from there onwards. Increasing levels of leisure time physical activity were associated with poorer high-density lipoprotein vasodilatory capacity. CONCLUSIONS In a high cardiovascular risk population, leisure time physical activity was associated not only with greater circulating levels of high-density lipoprotein-cholesterol, but also with better markers of high-density lipoprotein functionality, namely cholesterol efflux capacity, the capacity of high-density lipoprotein to esterify cholesterol and paraoxonase-1 antioxidant activity in individuals free of diabetes and lower cholesteryl ester transfer protein activity in individuals with type 2 diabetes.

[1]  Christopher N. Foley,et al.  Genetic Determinants of Lipids and Cardiovascular Disease Outcomes , 2019, Circulation. Genomic and precision medicine.

[2]  I. Buschmann,et al.  The impact of aerobic and isometric exercise on different measures of dysfunctional high-density lipoprotein in patients with hypertension , 2019, European journal of preventive cardiology.

[3]  R. Lamuela-Raventós,et al.  Increased Consumption of Virgin Olive Oil, Nuts, Legumes, Whole Grains, and Fish Promotes HDL Functions in Humans , 2019, Molecular nutrition & food research.

[4]  M. Sarzynski,et al.  Effects of exercise on HDL functionality , 2019, Current opinion in lipidology.

[5]  M. Guazzi,et al.  Exercise training for patients with type 2 diabetes and cardiovascular disease: What to pursue and how to do it. A Position Paper of the European Association of Preventive Cardiology (EAPC) , 2019, European journal of preventive cardiology.

[6]  M. Hernán,et al.  Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra‐Virgin Olive Oil or Nuts , 2018, The New England journal of medicine.

[7]  S. Nicholls,et al.  The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications , 2018, International journal of molecular sciences.

[8]  R. Shaw,et al.  AMPK: guardian of metabolism and mitochondrial homeostasis , 2017, Nature Reviews Molecular Cell Biology.

[9]  N. Smart,et al.  The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis , 2017, Cardiovascular Diabetology.

[10]  R. Shaw,et al.  AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. , 2017, Molecular cell.

[11]  John Everett Mumford,et al.  Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013 , 2016, British Medical Journal.

[12]  P. Urbánek,et al.  Redox regulation of FoxO transcription factors , 2015, Redox biology.

[13]  S. Popov,et al.  Exercise and NO production: relevance and implications in the cardiopulmonary system , 2015, Front. Cell Dev. Biol..

[14]  Darrel P Francis,et al.  Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117 411 patients , 2014, BMJ : British Medical Journal.

[15]  Ling Wang,et al.  The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. , 2014, Antioxidants & redox signaling.

[16]  Alex P. Reiner,et al.  Mendelian randomization of blood lipids for coronary heart disease , 2014, European heart journal.

[17]  P. Barter,et al.  Translation of High-Density Lipoprotein Function Into Clinical Practice: Current Prospects and Future Challenges , 2013, Circulation.

[18]  M. Aviram,et al.  Paraoxonase 1 activities, regulation, and interactions with atherosclerotic lesion , 2013, Current opinion in lipidology.

[19]  John Spertus,et al.  Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study , 2012, The Lancet.

[20]  Dolores Corella,et al.  Cohort profile: design and methods of the PREDIMED study. , 2012, International journal of epidemiology.

[21]  Dolores Corella,et al.  A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. , 2011, The Journal of nutrition.

[22]  E. Greer,et al.  AMP‐activated Protein Kinase and FoxO Transcription Factors in Dietary Restriction–induced Longevity , 2009, Annals of the New York Academy of Sciences.

[23]  N. Ruderman,et al.  AMPK and the biochemistry of exercise: implications for human health and disease. , 2009, The Biochemical journal.

[24]  Y. Ohashi,et al.  Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. , 2007, Archives of internal medicine.

[25]  A. Kontush,et al.  Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis , 2006, Pharmacological Reviews.

[26]  I. Chaudry,et al.  Sustained elevation of norepinephrine depresses hepatocellular function. , 2000, Biochimica et biophysica acta.

[27]  R. Elosua,et al.  Validation of the Minnesota Leisure Time Physical Activity Questionnaire In Spanish Women. Investigators of the MARATDON Group. , 2000, Medicine and science in sports and exercise.

[28]  R. Collins,et al.  Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. , 1999, American journal of epidemiology.

[29]  P. Barter,et al.  CHOLESTERYL ESTER TRANSFER PROTEIN: ITS ROLE IN PLASMA LIPID TRANSPORT , 1994, Clinical and experimental pharmacology & physiology.

[30]  R. Elosua,et al.  Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. , 1994, American journal of epidemiology.

[31]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[32]  P. Meikle,et al.  Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[33]  Corby K. Martin,et al.  Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[34]  A. Hoes,et al.  2016 European Guidelines on cardiovascular disease prevention in clinical practice. , 2016, Revista espanola de cardiologia.