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Original article

Vol. 143 No. 0102 (2013)

Genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors

  • David Conen
  • Tobias Schön
  • Stefanie Aeschbacher
  • Guillaume Paré
  • Walter Frehner
  • Martin Risch
  • Lorenz Risch
Cite this as:
Swiss Med Wkly. 2013;143:w13728


BACKGROUND:The pathogenesis of elevated blood pressure and other cardiovascular risk factors in the population and their progression over time is still incompletely understood, especially in young and healthy adults.

METHODS:The genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors (GAPP) study is a population-based prospective cohort study involving a representative sample of healthy adults aged 25–41 years in the Principality of Liechtenstein. Exclusion criteria are any cardiovascular disease, diabetes, obstructive sleep apnoea syndrome, daily intake of nonsteroidal anti-inflammatory drugs and a body mass index >35 kg/m². Examinations include detailed assessment of personal, medical, lifestyle and nutritional factors, standardised assessment of weight, height and waist circumference, blood pressure measurement (clinic and 24-hour ambulatory monitoring), electrocardiography (12-lead and 24-hour Holter monitoring), bioimpedance analysis, blood, urinary and genetic sampling, spirometry and sleep pulse oximetry with nasal flow measurement. Baseline examination is still ongoing. Follow-up examinations are scheduled every 3–5 years.

RESULTS:Since June 2010, 1,333 participants have been enrolled. Mean age of the participants was 36.7 ± 4.9 years and 47.5% of all participants were male. Mean body mass index was 26.1 ± 3.1 kg/m2 in men and 23.5 ± 3.9 kg/m2 in women. The prevalence of hypertension and prediabetes was 24.7% and 32.1% in men and 6% and 23% in women respectively. Mean LDL levels were 3.34 ± 0.9 mmol/l in men and 2.75 ± 0.7 mmol/l in women. Median hsCRP was 0.9 (0.5; 1.8) mg/l with no gender differences.

CONCLUSION:GAPP affords an excellent opportunity to assess genetic and phenotypic predictors of cardiovascular risk factors and their progression over time in young and healthy adults from the general population.


  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J.Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.
  2. Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D’Agostino RB, et al.Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002;287:1003–10.
  3. Conen D, Ridker PM, Buring JE, Glynn RJ.Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study. BMJ. 2007;335:432.
  4. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R.Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.
  5. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK.The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557–62.
  6. Hsu CY, McCulloch CE, Darbinian J, Go AS, Iribarren C.Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease. Arch Intern Med. 2005;165:923–8.
  7. Vasan RS, Larson MG, Leip EP, Evans JC, O’Donnell CJ, Kannel WB, et al.Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345:1291–7.
  8. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.
  9. Alberti KG, Zimmet PZ.Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet Med. 1998;15:539–53.
  10. Haslam DW, James WP.Obesity. Lancet. 2005;366:1197–209.
  11. Gelber RP, Gaziano JM, Manson JE, Buring JE, Sesso HD.A prospective study of body mass index and the risk of developing hypertension in men. Am J Hypertens. 2007;20:370–7.
  12. Niskanen L, Laaksonen DE, Nyyssonen K, Punnonen K, Valkonen VP, Fuentes R, et al.Inflammation, abdominal obesity, and smoking as predictors of hypertension. Hypertension. 2004;44:859–65.
  13. Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB.Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867–72.
  14. Conen D, Ridker PM, Mora S, Buring JE, Glynn RJ.Blood pressure and risk of developing type 2 diabetes mellitus: The Women’s Health Study. Eur Heart J. 2007;28:2937–43.
  15. Sesso HD, Buring JE, Chown MJ, Ridker PM, Gaziano JM.A prospective study of plasma lipid levels and hypertension in women. Arch Intern Med. 2005;165:2420–7.
  16. Tobin MD, Raleigh SM, Newhouse S, Braund P, Bodycote C, Ogleby J, et al.Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population. Circulation. 2005;112:3423–9.
  17. Levy D, DeStefano AL, Larson MG, O’Donnell CJ, Lifton RP, Gavras H, et al.Evidence for a gene influencing blood pressure on chromosome 17. Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham heart study. Hypertension. 2000;36:477–83.
  18. Conen D, Glynn RJ, Buring JE, Ridker PM, Zee RY.Natriuretic peptide precursor gene polymorphisms and risk of blood pressure progression and incident hypertension. Hypertension. 2007;50:1114–9.
  19. Conen D, Cheng S, Steiner LL, Buring JE, Ridker PM, Zee RY.Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: The Women’s Genome Health Study. J Hypertens. 2009;27:476–83.
  20. Conen D, Glynn RJ, Buring JE, Ridker PM, Zee RY.Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study. J Hypertens. 2008;26:1780–6.
  21. Newton-Cheh C, Larson MG, Vasan RS, Levy D, Bloch KD, Surti A, et al.Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nat Genet. 2009;41:348–53.
  22. The International Consortium for Blood Pressure Genome-Wide Association Studies.Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478:103–9.
  23. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, et al.International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381–95.
  24. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO.The Fagerstrom Test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991;86:1119–27.
  25. Denchev SV, Simova, II, Matveev MG.Evaluation of the SCHILLER BR-102 plus noninvasive ambulatory blood pressure monitor according to the International Protocol introduced by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension. Blood pressure monitoring. 2007;12:329–33.
  26. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al.Standardisation of spirometry. Eur Respir J: official journal of the European Society for Clinical Respiratory Physiology. 2005;26:319–38.
  27. Erman MK, Stewart D, Einhorn D, Gordon N, Casal E.Validation of the ApneaLink for the screening of sleep apnea: a novel and simple single-channel recording device. J Clin Sleep Med: official publication of the American Academy of Sleep Medicine. 2007;3:387–92.
  28. Weinreich G, Armitstead J, Topfer V, Wang YM, Wang Y, Teschler H.Validation of ApneaLink as screening device for Cheyne-Stokes respiration. Sleep. 2009;32:553–7.
  29. Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, et al.Multiple genetic loci for bone mineral density and fractures. N Engl J Med. 2008;358:2355–65.
  30. Ridker PM, Pare G, Parker A, Zee RY, Danik JS, Buring JE, et al.Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am J Hum Genet. 2008;82:1185–92.
  31. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, et al.Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40:189–97.
  32. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, et al.Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316:1331–6.
  33. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al.Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40:161–9.
  34. Cupples LA, Arruda HT, Benjamin EJ, D’Agostino RB, Sr., Demissie S, DeStefano AL, et al.The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports. BMC Med Genet. 2007;8(Suppl 1):S1.
  35. Ridker PM, Chasman DI, Zee RY, Parker A, Rose L, Cook NR, et al.Rationale, design, and methodology of the Women’s Genome Health Study: a genome-wide association study of more than 25,000 initially healthy American women. Clin Chem. 2008;54:249–55.
  36. Vollenweider P, Hayoz D, Preisig M, Pecoud A, Waterworth D, Mooser V, et al.L’etat de sante des Lausannois: premiers resultats de l’etude CoLaus. Rev Med Suisse. 2006;2:2528–30, 2532–3.
  37. Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, Zhao JH, et al.LDL-cholesterol concentrations: a genome-wide association study. Lancet. 2008;371:483–91.
  38. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Jr., et al.CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105–16.
  39. The Bogalusa Heart Study 20th anniversary symposium. Am J Med Sci. 1995;310(Suppl):S1–S138.
  40. McNamara JJ, Molot MA, Stremple JF, Cutting RT.Coronary artery disease in combat casualties in Vietnam. JAMA. 1971;216:1185–7.
  41. Tuzcu EM, Kapadia SR, Tutar E, Ziada KM, Hobbs RE, McCarthy PM, et al.High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation. 2001;103:2705–10.
  42. Wang NY, Young JH, Meoni LA, Ford DE, Erlinger TP, Klag MJ.Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study. Arch Intern Med. 2008;168:643–8.
  43. Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U.Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994;330:1041–6.
  44. Mancia G, De Backer G, Dominiczakc A, Cifkovad R, Fagarde R, Germanof G, et al.2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension. ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens. 2007;25:1751–62.
  45. American Diabetes A.Standards of medical care in diabetes – 2012. Diabetes care. 2012;35(Suppl 1):S11–63.

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