Skip to main content

Thank you for visiting nature.com. 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.

  • Original Article
  • Published:

Blood pressure and cardiovascular morbidity risk in type 2 diabetes with hypertension over a decade of follow-up: evidence for J-shaped phenomenon

Abstract

There is still debate on whether the relationship between blood pressure (BP) and risk of cardiovascular diseases (CVD) in patients with type 2 diabetes (T2D) is linear or not. Since these cardio-metabolic disturbances share interrelated complex pathogenic mechanisms, we aimed to assess the relationship of baseline systolic (SBP)/diastolic pressures with CVD and coronary heart disease (CHD) events in a cohort of Iranians with T2D during a median follow-up of 8.8 years. Of all 1009 eligible participants with T2D with a mean (s.d.) age of 54.4 (11.6) years and free of CVD at baseline, we primarily focused on 260 participants undergoing anti-hypertensive treatment. Multivariate Cox proportional hazard models were used to evaluate hazard ratios (HR) of BP categories for CVD and CHD events. Also, multivariable regression modelling was applied to obtain their risk curve. We detected a J-shaped phenomenon between the continuous baseline BP and risk of CVD events. Considering 130SBP<140 mm Hg as reference, a SBP 140 mm Hg was associated with increased CVD (HR [95% confidence interval (CI)]: 2.43 [1.23–4.82]) and CHD (HR [95% CI]: 2.05 [1.02–4.13]) risk. However, a SBP120 mm Hg in those with drug-treated hypertension also showed higher risk for CVD (HR [95% CI]: 2.80 [1.24–6.34]) and CHD events (HR [95% CI]: 2.39 [1.03–5.57]). Our findings revealed that the risk for macrovascular morbidity events was inversely associated with BP reduction below the level of 120/80 mm Hg for those with diabetes. People with diabetes might benefit from a BP management to a moderate range of 120/80–140/90 mm Hg for CVD risk reduction.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Williams B . Blood pressure and diabetes: a fatal attraction. Eur Heart J 2013; 34: 3395–3397.

    Article  Google Scholar 

  2. Weidmann P, Boehlen L, De Courten M, Ferrari P . Antihypertensive therapy in diabetic patients. J Hum Hypertens 1992; 6: S23–S36.

    PubMed  Google Scholar 

  3. Izzo R, de Simone G, Trimarco V, Gerdts E, Giudice R, Vaccaro O et al. Hypertensive target organ damage predicts incident diabetes mellitus. Eur Heart J 2013; 34: 3419–3426 eht281.

    Article  Google Scholar 

  4. Williams B . Treating hypertension in patients with diabetes: when to start and how low to go? JAMA 2015; 313 (6): 573–574.

    Article  CAS  Google Scholar 

  5. Wong ND . Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol 2014; 11 (5): 276–289.

    Article  Google Scholar 

  6. Derakhshan A, Sardarinia M, Khalili D, Momenan AA, Azizi F, Hadaegh F . Sex specific incidence rates of type 2 diabetes and its risk factors over 9 years of follow-up: Tehran Lipid and Glucose Study. PLoS ONE 2014; 9 (7): e102563.

    Article  Google Scholar 

  7. Bozorgmanesh M, Hadaegh F, Mohebi R, Ghanbarian A, Eskandari F, Azizi F . Diabetic population mortality and cardiovascular risk attributable to hypertension: a decade follow-up from the Tehran Lipid and Glucose Study. Blood Press 2013; 22 (5): 317–324.

    Article  CAS  Google Scholar 

  8. Adler AI, Stratton IM, Neil HAW, Yudkin JS, Matthews DR, Cull CA et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000; 321 (7258): 412–419.

    Article  CAS  Google Scholar 

  9. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003; 42 (6): 1206–1252.

    Article  CAS  Google Scholar 

  10. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J et al2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311 (5): 507–520.

    Article  CAS  Google Scholar 

  11. Group AS. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362 (17): 1575.

    Article  Google Scholar 

  12. Arguedas JA, Leiva V, Wright JM . Blood pressure targets for hypertension in people with diabetes mellitus. Database Syst Rev 2013; (10): CD008277.

  13. Bangalore S, Kumar S, Lobach I, Messerli FH . FH. blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose observations from traditional and bayesian random-effects meta-analyses of randomized trials. Circulation 2011; 123 (24): 2799–2810.

    Article  CAS  Google Scholar 

  14. Denardo SJ, Gong Y, Nichols WW, Messerli FH, Bavry AA, Cooper-DeHoff RM et al. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Am J Med 2010; 123 (8): 719–726.

    Article  Google Scholar 

  15. Fuchs F, Fuchs S . Blood pressure targets in the treatment of high blood pressure: a reappraisal of the J-shaped phenomenon. J Hum Hypertens 2014; 28 (2): 80–84.

    Article  CAS  Google Scholar 

  16. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373 (22): 2103–2116.

    Article  CAS  Google Scholar 

  17. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A . Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313 (6): 603–615.

    Article  Google Scholar 

  18. Azizi F, Rahmani M, Emami H, Mirmiran P, Hajipour R, Madjid M et al. Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1). Soz Praventivmed 2002; 47 (6): 408–426.

    Article  Google Scholar 

  19. Azizi F, Ghanbarian A, Momenan AA, Hadaegh F, Mirmiran P, Hedayati M et al. Prevention of non-communicable disease in a population in nutrition transition: Tehran Lipid and Glucose Study Phase II. Trials 2009; 10 (1): 5.

    Article  Google Scholar 

  20. Mohebi R, Mohebi A, Ghanbarian A, Momenan A, Azizi F, Hadaegh F . Is systolic blood pressure below 150 mm Hg an appropriate goal for primary prevention of cardiovascular events among elderly population? J Am Soc Hypertens 2014; 8 (7): 491–497.

    Article  Google Scholar 

  21. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150 (9): 604–612.

    Article  Google Scholar 

  22. Hadaegh F, Harati H, Ghanbarian A, Azizi F . Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study. Eur J Cardiovasc Prev Rehabil 2006; 13 (4): 571–577.

    Article  Google Scholar 

  23. Afsharian S, Akbarpour S, Abdi H, Sheikholeslami F, Moeini AS, Khalili D et al. Risk factors for cardiovascular disease and mortality events in adults with type 2 diabetes: a 10 year follow‐up: Tehran lipid and glucose study. Diabetes Metab Res Rev 2016; 32: 596–606.

    Article  CAS  Google Scholar 

  24. Chalise P, Chicken E, Mcgee D . Time Scales in Epidemiological Analysis: An Empirical Comparison. International Journal of Statistics and Probability 2016; 5: 91.

    Article  Google Scholar 

  25. Royston P, Sauerbrei W . Multivariable model-building: a pragmatic approach to regression anaylsis based on fractional polynomials for modelling continuous variables, vol. 777. John Wiley & Sons: Oxford, UK, 2008.

    Book  Google Scholar 

  26. Sauerbrei W, Royston P, Binder H . Selection of important variables and determination of functional form for continuous predictors in multivariable model building. Stat Med 2007; 26 (30): 5512–5528.

    Article  Google Scholar 

  27. Hellstrom H . The altered homeostatic theory: a hypothesis proposed to be useful in understanding and preventing ischemic heart disease, hypertension, and diabetes—including reducing the risk of age and atherosclerosis. Med Hypotheses 2007; 68 (2): 415–433.

    Article  CAS  Google Scholar 

  28. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006; 144 (12): 884–893.

    Article  Google Scholar 

  29. Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R et al. Prognostic value of blood pressure in patients with high vascular risk in the ongoing Telmisartan alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens 2009; 27 (7): 1360–1369.

    Article  CAS  Google Scholar 

  30. Bangalore S, Qin J, Sloan S, Murphy SA, Cannon CP and Investigators PI-TT. What is the optimal blood pressure in patients after acute coronary syndromes? Relationship of blood pressure and cardiovascular events in the pravastatin or atorvastatin evaluation and infection therapy–thrombolysis in myocardial infarction (PROVE IT-TIMI) 22 trial. Circulation 2010; 122 (21): 2142–2151.

    Article  CAS  Google Scholar 

  31. Cederholm J, Gudbjörnsdottir S, Eliasson B, Zethelius B, Eeg-Olofsson K, Nilsson PM . Blood pressure and risk of cardiovascular diseases in type 2 diabetes: further findings from the Swedish National Diabetes Register (NDR-BP II). J Hypertens 2012; 30 (10): 2020–2030.

    Article  CAS  Google Scholar 

  32. Bangalore S, Messerli FH, Wun C-C, Zuckerman AL, DeMicco D, Kostis JB et al. J-curve revisited: an analysis of blood pressure and cardiovascular events in the treating to new targets (TNT) trial. Eur Heart J 2010; 31: 2897–2908.

    Article  CAS  Google Scholar 

  33. Bangalore S, Kumar S, Volodarskiy A, Messerli FH . Blood pressure targets in patients with coronary artery disease: observations from traditional and Bayesian random effects meta-analysis of randomised trials. Heart 2013; 99 (9): 601–613.

    Article  Google Scholar 

  34. Li W, Katzmarzyk PT, Horswell R, Wang Y, Johnson J, Hu G . Blood pressure and all-cause mortality among patients with type 2 diabetes. Int J Cardiol 2016; 206: 116–121.

    Article  Google Scholar 

  35. Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC et al. Blood pressure and mortality in US veterans with chronic kidney disease: a cohort study. Ann Intern Med 2013; 159 (4): 233–242.

    Article  Google Scholar 

  36. Torre J, Bloomgarden Z, Dickey R, Hogan M, Janick J, Jyothinagaram S et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of hypertension. Endocr Pract 2006; 12 (2): 193–222.

    PubMed  Google Scholar 

  37. American Diabetes Association. Glycemic targets. Diabetes Care 2015; 38 (Supplement 1): S33–S40.

    Article  Google Scholar 

Download references

Acknowledgements

We express our appreciation to the participants of district 13, Tehran, for their enthusiastic support in this study. This study was supported by Grant No. 121 from the National Research Council of the Islamic Republic of Iran. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F Hadaegh.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Journal of Human Hypertension website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Riyahi-Alam, S., Derakhshan, A., Mansournia, M. et al. Blood pressure and cardiovascular morbidity risk in type 2 diabetes with hypertension over a decade of follow-up: evidence for J-shaped phenomenon. J Hum Hypertens 31, 415–421 (2017). https://doi.org/10.1038/jhh.2016.94

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2016.94

This article is cited by

Search

Quick links