Open Access Protocol BMJ Open: first published as 10.1136/bmjopen-2016-011031 on 7 June 2016. Downloaded from Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross- sectional, descriptive observational study Manuel A Gomez-Marcos,1,2 Carlos Martinez-Salgado,3 Rogelio Gonzalez-Sarmiento,4,5 Jesus Ma Hernandez-Rivas,6,7,8 Pedro L Sanchez-Fernandez,9,10 Jose I Recio-Rodriguez,11 Emiliano Rodriguez-Sanchez,1,2 Luis García-Ortiz12,13 To cite: Gomez-Marcos MA, ABSTRACT Strengths and limitations of this study Martinez-Salgado C, Introduction: The process of population ageing that is Gonzalez-Sarmiento R, et al. occurring in developed societies represents a major ▪ Association between different This study selected, by random sampling of the challenge for the health system. The aim of this study risk factors and vascular population, participants aged between 35 and accelerated ageing (EVA is to analyse factors that have an influence on early 75 years. study): study protocol for a vascular ageing (EVA), estimated by carotid-femoral ▪ Assesses arterial ageing by the pulse wave vel- cross-sectional, descriptive pulse wave velocity (cf-PWV) and Cardio Ankle ocity and Cardio Ankle Vascular Index (CAVI) observational study. BMJ Vascular Index (CAVI), and to determine differences by arterial stiffness tests. Open 2016;6:e011031. gender in a Spanish population. ▪ Analyses the influence of diet, exercise, smoking doi:10.1136/bmjopen-2016- Methods and analysis: An observational, and psychological factors on early vascular 011031 descriptive, cross-sectional study. ageing (EVA). Study population: From the population assigned to ▪ Assesses the influence of molecules of inflam- ▸ Prepublication history for the participating healthcare centres, a cluster random mation and oxidative stress in EVA. this paper is available online. sampling stratified by age and gender will be ▪ Analyses the telomere length and its association http://bmjopen.bmj.com/ To view these files please performed to obtain 500 participants aged between 35 with vascular stiffness. visit the journal online and 75. Those who meet the inclusion criteria and give (http://dx.doi.org/10.1136/ written informed consent will be included in the study. bmjopen-2016-011031). Measurements: Main dependent variables: cf-PWV INTRODUCTION Received 2 January 2016 determined using the SphygmoCor System and CAVI The process of population ageing that is Revised 19 April 2016 estimated using VASERA. Secondary dependent occurring in developed societies represents a Accepted 13 May 2016 variables: telomere length, carotid intima-media major challenge for the health system. thickness, central and peripheral augmentation index, Cardiovascular diseases (CVD) are the most on September 26, 2021 by guest. Protected copyright. ankle-brachial pulse wave velocity, ankle-brachial index, common cause of morbidity and mortality in retinal arteriovenous index, and renal and cardiac organ the world, representing half of the deaths in damage. Independent variables: lifestyles (physical persons aged over 65 years and affecting activity, adherence to the Mediterranean diet, alcohol >70% of patients with diabetes mellitus. The and tobacco consumption); psychological factors fi (depression, anxiety and chronic stress); inflammatory non-modi able cause of vascular ageing in factors and oxidative stress. healthy adults is age, because it causes Ethics and dissemination: The study has been increased arterial stiffness and changes in approved by the clinical research ethics committee of chromosome replication with telomere the healthcare area of Salamanca. All study participants shortening.12 will sign an informed consent form agreeing to The comparison of biological age with participate in the study in compliance with the chronological age allows us to establish if the Declaration of Helsinki and the WHO standards for pattern of vascular ageing is at an expected observational studies. The results of this study will or accelerated rate, that is, if early vascular For numbered affiliations see allow the understanding of the relationship of the ageing (EVA) is present or not.12 end of article. different influencing factors and their relative weight in Arterial stiffness and ageing: Arterial stiffness the development of EVA. At least 5 publications in first- increases with age even in healthy adults.3 It Correspondence to quartile scientific journals are planned. Dr Manuel A Gomez-Marcos; Trial registration number: NCT02623894; Pre-results. involves changes in vascular structure with [email protected] thickening of the arterial wall, changes in Gomez-Marcos MA, et al. BMJ Open 2016;6:e011031. doi:10.1136/bmjopen-2016-011031 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2016-011031 on 7 June 2016. Downloaded from vascular function due to increased stiffness, and lower arterial stiffness and lower carotid intima-media decreased wall distensibility of large arteries, associated thickness (IMT).21 22 In contrast, in sedentary healthy with endothelial dysfunction and pulse wave changes.34 adults, ageing is associated with increased stiffness of the These changes are primarily mediated by nitric oxide.1 large elastic arteries and with poorer vascular endothe- Arterial ageing is a multifactorial process associated with lial function and increased mortality.22 23 The EVIDENT changes in structure and function of the large arteries.1 study found an association of physical activity with better These changes are related to age, and are accelerated in vascular structure and function and sedentary time – the presence of associated CVD,5 9 cardiovascular risk (hours spent watching television) with greater arterial factors or cardio-unhealthy lifestyles.10 Some of these stiffness.24 However, there are some points that are still factors are controllable, and a greater understanding of unresolved such as the effect of endurance exercises, the links existing between vascular ageing, lifestyle and alone or combined with aerobic exercises, on vascular CVD will help find strategies geared to preventing or ageing.22 In addition, physical activity improves endothe- delaying this ageing.11 12 lial function, increases the bioavailability of nitric oxide Telomere length and vascular ageing: Somatic ageing starts and reduces the presence of oxidative stress and inflam- when telomerase activity decreases and prevents accurate matory agents, such as tumour necrosis factor-α copies of chromosome replication being made in the (TNF-α).25 Therefore, physical activity favourably modu- distal end, resulting in a decreased telomere length.13 lates several expressions of vascular ageing, thereby pre- Although telomerase activity is genetically determined, it serving vascular function and possibly reducing CVD is also sensitive to the action of external factors.1 In add- risk.12026 ition to ageing, inflammation and oxidative stress are Diet and vascular ageing: The Mediterranean diet is cur- endogenous factors causing telomere shortening.14 rently considered the epitome of a healthy diet. There is Telomere length is also correlated with lifestyle.14 evidence that it improves vascular ageing27 28 and endo- A reduced activity genotype causes a greater degree of thelial function,29 30 increasing the number of endothe- vulnerability to triggering factors such as sedentary life- lial cells and reducing vascular inflammation, oxidative style, hypertension, obesity, hyperlipidaemia, diabetes, stress and postprandial oxidative stress markers.29 30 An stress and smoking.13 The intimate relationship between omega-3 rich diet improves vascular ageing27 28 and a the action of telomerase and morbidity and mortality caloric-restricted diet improves vascular structure and has been documented in different studies.13 Rode et al15 function.31 The PREDIMED study (Prevention with a analysed 64 637 individuals from the general population Mediterranean Diet) has shown that participants in the and concluded that short telomeres in peripheral blood intervention groups (Mediterranean diet) could reduce leucocytes were associated with high mortality for indivi- the incidence of major cardiovascular complications by 32 duals in the short test versus the longest decile. In 1525 30% at 4 years of follow-up. http://bmjopen.bmj.com/ postmenopausal women with a follow-up of 13 years, Psychological factors and vascular ageing: Depression Carty et al16 found that white women with a shorter increases the risk of coronary disease (CD),33 predicts leucocyte telomere length (LTL) had higher risks of the increase in mortality after angioplasty or coronary mortality and coronary heart disease. In contrast, surgery,34 35 increases the risk of cerebrovascular shorter LTL was weakly associated with decreased mor- disease,36 and increases mortality and the number of tality hazard in African-American women. Simpson admissions in participants with heart failure (HF).37 38 et al,17 in patients with cancer, concluded that the fuso- Anxiety disorders have also been associated with 39 genic telomere length threshold provides a powerful, increased cardiac mortality and CD. In the on September 26, 2021 by guest. Protected copyright. independent prognostic marker with clinical utility in INTERHEART study,40 participants who had a first myo- breast cancer. Additionally, Needham et al18 examined cardial infarction showed stress levels at work, stress at the association between LTL and mortality in 3091 US home, general and permanent stress greater