Molecular and Cellular Biochemistry

, Volume 455, Issue 1–2, pp 61–71 | Cite as

Hypertension and longevity: role of genetic polymorphisms in renin-angiotensin-aldosterone system and endothelial nitric oxide synthase

  • Alda Pereira da SilvaEmail author
  • Andreia Matos
  • Laura Aguiar
  • Nuno Ramos-Marques
  • Ricardo Ribeiro
  • Ângela Gil
  • João Gorjão-Clara
  • Manuel Bicho


Hypertension (HT), a common age-related disorder, is an important risk factor for cardiovascular disease. This study aims to identify the prevalence of HT in Portuguese centenarians and evaluate whether gene polymorphisms encoding key molecules in blood pressure (BP) regulation are associated with longevity. There were recruited 253 centenarians (100.26 ± 1.98 years) and 268 control subjects (67.51 ± 3.25 years). Hypertension (ESH/ESC2013 and JNC8) and diabetes (WHO) were evaluate. Genetic polymorphisms of renin-angiotensin-aldosterone system (RAAS) and NOS3 were determined. The prevalence of HT among centenarians was 64.4% and the majority (58.9%) were controlled, differing from control group both on frequency (P < 0.001) and on their control (P < 0.001). We found that HT is a risk factor for not achieving longevity (OR 2.531, 95% CI 1.688–3.793, P < 0.001), the same for diabetes (OR 5.669 95% CI 2.966–10.835, P < 0.001), and male gender (OR 2.196, 95% CI 1.493–3.29, P < 0.001). Hypertension, adjusted for gender and diabetes, was independent risk factor anti-longevity (OR 2.007, 95% CI 1320–3.052, P = 0.001). The ACE_D and NOS3_G alleles were more frequent in centenarians compared to controls (P < 0.001, both cases). ACE_II and NOS3_TT genotypes, adjusted for BP, gender and diabetes, increased risk in 3.748 (95% CI 1.887–7.444) and 2.533 (95% CI 1.483–4.327), respectively, in relation to ACE_DD (P < 0.001) and NOS3_GG (P = 0.001), against longevity. Our findings suggest that the prevalence of hypertension was lower in Portuguese centenarians than in the elderly, reinforcing the importance of better cardiovascular risk profiles to achieve longevity even in the presence of genetic condition.


Hypertension Centenarians ACE NOS3 Genetic polymorphism Longevity 



The authors would like to thank for the support given: Fausto Pinto (MD, PhD) Dean of Faculdade de Medicina da Universidade de Lisboa and Director of Department of Heart and Vessels of Hospital de Santa Maria; Dulce Brito (MD, PhD), Department of Cardiology, Hospital Santa Maria; António Nunes Diogo (MD) and Armando Bordalo (MD), UTIC/Arsénio Cordeiro Department, Hospital Santa Maria; Brás Nogueira (MD, PhD), Hypertension Department, Hospital Santa Maria; Lúcio Botas (MD, PhD), Department of Cardiology outpatients, Hospital Santa Maria; Susana Rodrigues Santos (PhD), HeartGenetics, Genetics and Biotechnology. Finally, thanks to Sara Cardoso (Social Researcher and Writer, Lisboa) for the precious help in establishing contacts and to César Oliveira for operational collaboration in the fieldwork.

Compliance with ethical standards

Conflict of interest

The author declares that they have no competing interests.

Ethical approval

The experiments comply with the current laws of Portugal in which the work was performed.


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Authors and Affiliations

  1. 1.Genetics Laboratory and Environmental Health Institute-ISAMBFaculdade de Medicina da Universidade de LisboaLisbonPortugal
  2. 2.Instituto de Investigação Bento da Rocha CabralLisbonPortugal
  3. 3.Universitary Geriatric Unit of Faculdade de MedicinaUniversidade de LisboaLisbonPortugal
  4. 4.Centro Hospitalar Lisboa CentralLisbonPortugal
  5. 5.Molecular Oncology GroupPortuguese Institute of OncologyPortoPortugal
  6. 6.Academic Medical Centre of Lisboa - North of Lisboa Hospital CentreLisbonPortugal
  7. 7.Genetics Laboratory and Environmental Health Institute (ISAMB), Faculty of MedicineLisbon UniversityLisbonPortugal

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