Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Exploring and comparing definitions of healthy vascular ageing in the population: characteristics and prospective cardiovascular risk


Different methods can be used to define healthy vascular ageing (HVA). In this prospective cohort study, we explored three different definitions in order to provide guidance for which to use. 2718 subjects were included from the Cardiovascular (CV) arm of the Malmö Diet Cancer Study (MDCS; median age 71.9 years, 62.2% females). Three different definitions of HVA were used: HVA-1 (<15th percentile of aortic pulse wave velocity (aPWV) distribution from age-quintiles); HVA-2 (<35th percentile of aPWV+ <35th percentile of carotid Intima-Media Thickness. cIMT); and HVA-3 (aPWV < 7.6 m/s + no hypertension). The HVA-1 and HVA-2 groups were compared with the HVA-3, and to the corresponding groups without HVA (non-HVA), in cross-sectional analyses for baseline characteristics and using Cox regressions for prospective risk, yielding hazard ratios (HRs) adjusted for conventional risk factors. A composite CVD endpoint was used, consisting of myocardial infarctions, ischemic heart disease mortality, and coronary artery procedures. The baseline characteristics were, with minor exceptions, similar across HVA groups. In the fully adjusted model, the HRs (95%CI) were 0.62 (0.41–0.93), 0.45 (0.26–0.76), and 0.56 (0.34–0.91) for HVA-1, HVA-2, and HVA-3, respectively. In summary, this observational study of elderly subjects provides examples of integrating hypertension and cIMT in the definition of HVA, as compared with only using aPWV. As aPWV itself is such a robust marker of HVA, it is demanding to find additional markers which improve the definition. There is a need to create a generally accepted definition of HVA.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Inclusion/exclusion flowchart for the Malmö Diet Cancer Study—Cardiovascular Arm.
Fig. 2: Venn diagram showing overlap between the three HVA (1–3) definitions.
Fig. 3: Cumulative CVD events based on the three HVA (1–3) definitions.

Code availability

The statistical analyses were done using “R: A language and environment for statistical computing”, version 3.4.2 for Windows 64 bit. The package “Regression Modeling Strategies”, version 5.1-2 ( was used for the regressions. The code used for the analyses can be accessed by contacting the author Benjamin Nilsson Wadström at:


  1. Groenewegen KA, den Ruijter HM, Pasterkamp G, Polak JF, Bots ML, Peters SA. Vascular age to determine cardiovascular disease risk: a systematic review of its concepts, definitions, and clinical applications. Eur J Prev Cardiol. 2016;23:264–74.

    Article  CAS  Google Scholar 

  2. Terentes-Printzios D, Vlachopoulos C, Xaplanteris P, Ioakeimidis N, Aznaouridis K, Baou K, et al. Cardiovascular risk factors accelerate progression of vascular aging in the general population: results from the CRAVE study (Cardiovascular Risk Factors Affecting Vascular Age). Hypertension. 2017;70:1057–64.

    Article  CAS  Google Scholar 

  3. Fine I, Kuznik BI, Kaminsky AV, Shenkman L, Kustovsjya EM, Maximova OG. New noninvasive index for evaluation of the vascular age of healthy and sick people. J Biomed Opt. 2012;17:087002–1.

    Article  Google Scholar 

  4. Fortier C, Sidibe A, Desjardins MP, Marquis K, De Serres SA, Mac-Way F, et al. Aortic-Brachial pulse wave velocity ratio: a blood pressure-independent index of vascular aging. Hypertension. 2017;69:96–101.

    Article  CAS  Google Scholar 

  5. Nilsson Wadstrom B, Fatehali AH, Engstrom G, Nilsson PM. A vascular aging index as independent predictor of cardiovascular events and total mortality in an elderly urban population. Angiology. 2019;70:929–37.

  6. Niiranen TJ, Lyass A, Larson MG, Hamburg NM, Benjamin EJ, Mitchell GF, et al. Prevalence, correlates, and prognosis of healthy vascular aging in a western community-dwelling cohort: the Framingham heart study. Hypertension. 2017;70:267–74.

    Article  CAS  Google Scholar 

  7. Ji H, Teliewubai J, Lu Y, Xiong J, Yu S, Chi C, et al. Vascular aging and preclinical target organ damage in community-dwelling elderly: the Northern Shanghai Study. J Hypertens. 2018;36:1391–8.

    Article  CAS  Google Scholar 

  8. Yang Y, Wang A, Yuan X, Zhao Q, Liu X, Chen S, et al. Association between healthy vascular aging and the risk of the first stroke in a community-based Chinese cohort. Aging. 2019;11:5807–16.

    Article  CAS  Google Scholar 

  9. Nowak KL, Rossman MJ, Chonchol M, Seals DR. Strategies for achieving healthy vascular aging. Hypertension. 2018;71:389–402.

    Article  CAS  Google Scholar 

  10. Laurent S, Boutouyrie P, Cunha PG, Lacolley P, Nilsson PM. Concept of extremes in vascular aging. Hypertension. 2019;74:218–28.

  11. Gurven M, Blackwell AD, Rodriguez DE, Stieglitz J, Kaplan H. Does blood pressure inevitably rise with age?: longitudinal evidence among forager-horticulturalists. Hypertension. 2012;60:25–33.

    Article  CAS  Google Scholar 

  12. Carvalho JJ, Baruzzi RG, Howard PF, Poulter N, Alpers MP, Franco LJ, et al. Blood pressure in four remote populations in the INTERSALT Study. Hypertension. 1989;14:238–46.

    Article  CAS  Google Scholar 

  13. Stevenson DR. Blood pressure and age in cross-cultural perspective. Hum Biol. 1999;71:529–51.

    CAS  PubMed  Google Scholar 

  14. Timio M, Lippi G, Venanzi S, Gentili S, Quintaliani G, Verdura C, et al. Blood pressure trend and cardiovascular events in nuns in a secluded order: a 30-year follow-up study. Blood Press. 1997;6:81–7.

    Article  CAS  Google Scholar 

  15. Lemogoum D, Ngatchou W, Janssen C, Leeman M, Van Bortel L, Boutouyrie P, et al. Effects of hunter-gatherer subsistence mode on arterial distensibility in Cameroonian pygmies. Hypertension. 2012;60:123–8.

    Article  CAS  Google Scholar 

  16. Ishida A, Fujisawa M, Del Saz EG, Okumiya K, Kimura Y, Manuaba IIB, et al. Arterial stiffness, not systolic blood pressure, increases with age in native Papuan populations. Hypertens Res. 2018;41:539–46.

    Article  CAS  Google Scholar 

  17. Nilsson PM, Laurent S, Cunha PG, Olsen MH, Rietzschel E, Franco OH, et al. Characteristics of healthy vascular ageing in pooled population-based cohort studies: the global Metabolic syndrome and Artery REsearch Consortium. J Hypertens. 2018;36:2340–9.

    Article  CAS  Google Scholar 

  18. Vlachopoulos C, Xaplanteris P, Aboyans V, Brodmann M, Cifkova R, Cosentino F, et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society. Atherosclerosis. 2015;241:507–32.

    Article  CAS  Google Scholar 

  19. Rosvall M, Ostergren PO, Hedblad B, Isacsson SO, Janzon L, Berglund G. Occupational status, educational level, and the prevalence of carotid atherosclerosis in a general population sample of middle-aged Swedish men and women: results from the Malmo Diet and Cancer Study. Am J Epidemiol. 2000;152:334–46.

    Article  CAS  Google Scholar 

  20. Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M, et al. The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev. 2001;10:489–99.

    Article  CAS  Google Scholar 

  21. Rosvall M, Persson M, Östling G, Nilsson PM, Melander O, Hedblad B, et al. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmö Diet and Cancer Study. Atherosclerosis. 2015;239:615–21.

    Article  CAS  Google Scholar 

  22. Berglund G, Elmstahl S, Janzon L, Larsson SA. The Malmo Diet and Cancer study. Design and feasibility. J Intern Med. 1993;233:45–51.

    Article  CAS  Google Scholar 

  23. Gottsäter M, Östling G, Persson M, Engström G, Melander O, Nilsson PM. Non-hemodynamic predictors of arterial stiffness after 17 years of follow-up: the Malmö Diet and Cancer study. J Hypertens. 2015;33:957–65.

    Article  Google Scholar 

  24. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30:445–8.

    Article  Google Scholar 

  25. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.

    Article  Google Scholar 

  26. Koul S, Smith JG, Schersten F, James S, Lagerqvist B, Erlinge D. Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J. 2011;32:2989–97.

    Article  CAS  Google Scholar 

  27. Persson M, Ostling G, Smith G, Hamrefors V, Melander O, Hedblad B, et al. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease. Stroke. 2014;45:18–23.

    Article  CAS  Google Scholar 

  28. Weber T, Wassertheurer S, Hametner B, Moebus S, Pundt N, Mahabadi AA, et al. Cross-sectional analysis of pulsatile hemodynamics across the adult life span: reference values, healthy and early vascular aging: the Heinz Nixdorf Recall and the MultiGeneration Study. J Hypertens. 2019;37:2404–13.

  29. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol. 2014;63:636–46.

    Article  Google Scholar 

Download references


We thank Gerd Östling, PhD, and Cecilia Kennbäck, ultrasound technicians at the clinical sciences department, responsible for aPWV and cIMT data collection. We also thank Associate Professor Margaretha Persson, responsible for study logistics and flow.


The study was supported by the Research Council of Sweden [grant number K2011-65X-20752-04-6]; the Region Skane County Council; the Heart- and Lung Foundation and the Ernhold Lundstrom Foundation to PM Nilsson.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Peter M. Nilsson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nilsson Wadström, B., Engström, G. & Nilsson, P.M. Exploring and comparing definitions of healthy vascular ageing in the population: characteristics and prospective cardiovascular risk. J Hum Hypertens 35, 428–436 (2021).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links