Diabetes Metab J.  2019 Jun;43(3):350-367. 10.4093/dmj.2018.0108.

Association of Visit-to-Visit Variability of Blood Pressure with Cardiovascular Disease among Type 2 Diabetes Mellitus Patients: A Cohort Study

• Yu ZB
• Li D
• Chen XY
• Zheng PW
• Lin HB
• Tang ML
• Jin MJ
• Wang JB
• Chen K

• KMID: 2454062
• DOI: http://doi.org/10.4093/dmj.2018.0108

Abstract

BACKGROUND
Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China.
METHODS
We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. The VVV of BP was calculated using five metrics, including standard deviation (SD), coefficient of variation (CV), variation independent of mean, average real variability, and successive variability (SV) of measurements, obtained over a 24-month measurement period. Hazard ratios and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression models for the associations of variability in BP with risk of CVD.
RESULTS
A total of 894 CVD events were observed during a median follow-up of 49.5 months. The hazard ratio in the highest quintile of SD of SBP was 1.24 (95% CI, 1.01 to 1.52) compared with patients in the lowest quintile. The association between higher VVV of DBP and risk of CVD was not consistent across different metrics and sensitivity analyses.
CONCLUSION
Higher VVV of SBP was associated with an increased risk of CVD, irrespective of the mean SBP level. Future studies are needed to confirm these findings.

Keyword

Blood pressure; Cardiovascular diseases; Diabetes mellitus, type 2

MeSH Terms

Blood Pressure*
Cardiovascular Diseases*
China
Cohort Studies*
Diabetes Mellitus, Type 2*
Follow-Up Studies
Humans
Retrospective Studies

Figure

• 

  Fig. 1 Study design for the investigation of the association of visit-to-visit variability (VVV) in blood pressure (BP) and cardiovascular disease (CVD). The BP measurements during the measurement period (0, 3, 6, 9, 12, 15, 18, 21, 24 months after baseline) were used to calculate the mean and VVV. The median follow-up period was 49.5 months.

• 

  Fig. 2 Hazard ratio (95% confidence interval [CI]) for cardiovascular disease of Q5 compared to Q1 of standard deviation of systolic blood pressure (SBP) in different subgroups. Data were adjusted for sex, age, smoking status, alcohol drinking status, duration of diabetes mellitus, body mass index, baseline fasting plasma glucose, use of blood glucose treatment, use of antihypertensive drugs, use of lipid lowering drugs and mean SBP values. Baseline low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, and triglycerides were further adjusted when patients without baseline lipid profiles were excluded. BP, blood pressure; DM, diabetes mellitus.

Reference

1. International Diabetes Federation. IDF diabetes atlas. 8th ed. Brussels: International Diabetes Federation;2017.

2. International Diabetes Federation Guideline Development Group. Global guideline for type 2 diabetes. Diabetes Res Clin Pract. 2014; 104:1–52. PMID: 24508150.

3. American Diabetes Association. Standards of medical care in diabetes: 2015 abridged for primary care providers. Clin Diabetes. 2015; 33:97–111. PMID: 25897193.

4. Parati G, Ochoa JE, Salvi P, Lombardi C, Bilo G. Prognostic value of blood pressure variability and average blood pressure levels in patients with hypertension and diabetes. Diabetes Care. 2013; 36(Suppl 2):S312–S324. PMID: 23882065.

5. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, McManus RJ. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ. 2016; 354:i4098. PMID: 27511067.

6. Grove JS, Reed DM, Yano K, Hwang LJ. Variability in systolic blood pressure: a risk factor for coronary heart disease? Am J Epidemiol. 1997; 145:771–776. PMID: 9143206.

7. Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010; 375:895–905. PMID: 20226988.

8. Lau KK, Wong YK, Teo KC, Chang RS, Chan KH, Hon SF, Wat KL, Cheung RT, Li LS, Siu CW, Tse HF. Long-term prognostic implications of visit-to-visit blood pressure variability in patients with ischemic stroke. Am J Hypertens. 2014; 27:1486–1494. PMID: 24842389.

9. Wu Z, Jin C, Vaidya A, Jin W, Huang Z, Wu S, Gao X. Longitudinal patterns of blood pressure, incident cardiovascular events, and all-cause mortality in normotensive diabetic people. Hypertension. 2016; 68:71–77. PMID: 27217407.

10. McMullan CJ, Lambers Heerspink HJ, Parving HH, Dwyer JP, Forman JP, de Zeeuw D. Visit-to-visit variability in blood pressure and kidney and cardiovascular outcomes in patients with type 2 diabetes and nephropathy: a post hoc analysis from the RENAAL study and the Irbesartan Diabetic Nephropathy Trial. Am J Kidney Dis. 2014; 64:714–722. PMID: 25064674.

11. Kilpatrick ES, Rigby AS, Atkin SL. The role of blood pressure variability in the development of nephropathy in type 1 diabetes. Diabetes Care. 2010; 33:2442–2447. PMID: 20798339.

12. Wang J, Shi X, Ma C, Zheng H, Xiao J, Bian H, Ma Z, Gong L. Visit-to-visit blood pressure variability is a risk factor for all-cause mortality and cardiovascular disease: a systematic review and meta-analysis. J Hypertens. 2017; 35:10–17. PMID: 27906836.

13. Wan EY, Fung CS, Yu EY, Fong DY, Chen JY, Lam CL. Association of visit-to-visit variability of systolic blood pressure with cardiovascular disease and mortality in primary care Chinese patients with type 2 diabetes: a retrospective population-based cohort study. Diabetes Care. 2017; 40:270–279. PMID: 27899498.

14. Ohkuma T, Woodward M, Jun M, Muntner P, Hata J, Colagiuri S, Harrap S, Mancia G, Poulter N, Williams B, Rothwell P, Chalmers J. ADVANCE Collaborative Group. Prognostic value of variability in systolic blood pressure related to vascular events and premature death in type 2 diabetes mellitus: the ADVANCE-ON study. Hypertension. 2017; 70:461–468. PMID: 28584014.

15. Hsieh YT, Tu ST, Cho TJ, Chang SJ, Chen JF, Hsieh MC. Visit-to-visit variability in blood pressure strongly predicts all-cause mortality in patients with type 2 diabetes: a 5·5-year prospective analysis. Eur J Clin Invest. 2012; 42:245–253. PMID: 21815887.

16. Hata J, Arima H, Rothwell PM, Woodward M, Zoungas S, Anderson C, Patel A, Neal B, Glasziou P, Hamet P, Mancia G, Poulter N, Williams B, Macmahon S, Chalmers J. ADVANCE Collaborative Group. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation. 2013; 128:1325–1334. PMID: 23926207.

17. Takao T, Kimura K, Suka M, Yanagisawa H, Kikuchi M, Kawazu S, Matsuyama Y. Relationships between the risk of cardiovascular disease in type 2 diabetes patients and both visit-to-visit variability and time-to-effect differences in blood pressure. J Diabetes Complications. 2015; 29:699–706. PMID: 25861721.

18. Malik MO, Govan L, Petrie JR, Ghouri N, Leese G, Fischbacher C, Colhoun H, Philip S, Wild S, McCrimmon R, Sattar N, Lindsay RS. Scottish Diabetes Research Network Epidemiology Group. Ethnicity and risk of cardiovascular disease (CVD): 4.8 year follow-up of patients with type 2 diabetes living in Scotland. Diabetologia. 2015; 58:716–725. PMID: 25669630.

19. Zheng PW, Wang JB, Zhang ZY, Shen P, Chai PF, Li D, Jin MJ, Tang ML, Lu HC, Lin HB, Chen K. Air pollution and hospital visits for acute upper and lower respiratory infections among children in Ningbo, China: a time-series analysis. Environ Sci Pollut Res Int. 2017; 24:18860–18869. PMID: 28653196.

20. Lin H, Zhang D, Shen P, Xu Z, Si Y, Tang X, Gao P. Abstract P166: Multimorbidity and risk of mortality in China: results from the Chinese Electronic Health Records Research in Yinzhou (CHERRY) Study. Circulation. 2018; 135(Suppl 1):AP166.

21. Revision Committee of China Hypertension Primary Care Management Guideline. Guideline for Chinese hypertension primary care management (2014 edition) [in Chinese]. China J Hypertens. 2015; 23:24–43.

22. Schutte R, Thijs L, Liu YP, Asayama K, Jin Y, Odili A, Gu YM, Kuznetsova T, Jacobs L, Staessen JA. Within-subject blood pressure level: not variability: predicts fatal and nonfatal outcomes in a general population. Hypertension. 2012; 60:1138–1147. PMID: 23071126.

23. Johansson JK, Niiranen TJ, Puukka PJ, Jula AM. Prognostic value of the variability in home-measured blood pressure and heart rate: the Finn-Home Study. Hypertension. 2012; 59:212–218. PMID: 22215704.

24. Hata Y, Kimura Y, Muratani H, Fukiyama K, Kawano Y, Ashida T, Yokouchi M, Imai Y, Ozawa T, Fujii J, Omae T. Office blood pressure variability as a predictor of brain infarction in elderly hypertensive patients. Hypertens Res. 2000; 23:553–560. PMID: 11131265.

25. Muntner P, Shimbo D, Tonelli M, Reynolds K, Arnett DK, Oparil S. The relationship between visit-to-visit variability in systolic blood pressure and all-cause mortality in the general population: findings from NHANES III, 1988 to 1994. Hypertension. 2011; 57:160–166. PMID: 21200000.

26. Takao T, Matsuyama Y, Suka M, Yanagisawa H, Iwamoto Y. The combined effect of visit-to-visit variability in HbA1c and systolic blood pressure on the incidence of cardiovascular events in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2015; 3:e000129.

27. Ushigome E, Fukui M, Hamaguchi M, Senmaru T, Sakabe K, Tanaka M, Yamazaki M, Hasegawa G, Nakamura N. The coefficient variation of home blood pressure is a novel factor associated with macroalbuminuria in type 2 diabetes mellitus. Hypertens Res. 2011; 34:1271–1275. PMID: 21814212.

28. Tamura K, Azushima K, Umemura S. Day-by-day home-measured blood pressure variability: another important factor in hypertension with diabetic nephropathy. Hypertens Res. 2011; 34:1249–1250. PMID: 21866109.

29. Okada H, Fukui M, Tanaka M, Inada S, Mineoka Y, Nakanishi N, Senmaru T, Sakabe K, Ushigome E, Asano M, Yamazaki M, Hasegawa G, Nakamura N. Visit-to-visit variability in systolic blood pressure is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes. Atherosclerosis. 2012; 220:155–159. PMID: 22100253.

30. Sohn MW, Epstein N, Huang ES, Huo Z, Emanuele N, Stukenborg G, Guihan M, Li J, Budiman-Mak E. Visit-to-visit systolic blood pressure variability and microvascular complications among patients with diabetes. J Diabetes Complications. 2017; 31:195–201. PMID: 27671535.

31. Juhanoja EP, Niiranen TJ, Johansson JK, Puukka PJ, Thijs L, Asayama K, Langen VL, Hozawa A, Aparicio LS, Ohkubo T, Tsuji I, Imai Y, Stergiou GS, Jula AM, Staessen JA. International Database on Home Blood Pressure in Relation to Cardiovascular Outcome (IDHOCO) Investigators. Outcome-driven thresholds for increased home blood pressure variability. Hypertension. 2017; 69:599–607. PMID: 28193705.

32. Muntner P, Whittle J, Lynch AI, Colantonio LD, Simpson LM, Einhorn PT, Levitan EB, Whelton PK, Cushman WC, Louis GT, Davis BR, Oparil S. Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality: a cohort study. Ann Intern Med. 2015; 163:329–338. PMID: 26215765.

33. Hughes MD, Pocock SJ. Within-subject diastolic blood pressure variability: implications for risk assessment and screening. J Clin Epidemiol. 1992; 45:985–998. PMID: 1432027.

34. Yeh CH, Yu HC, Huang TY, Huang PF, Wang YC, Chen TP, Yin SY. The risk of diabetic renal function impairment in the first decade after diagnosed of diabetes mellitus is correlated with high variability of visit-to-visit systolic and diastolic blood pressure: a case control study. BMC Nephrol. 2017; 18:99. PMID: 28330451.

35. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation. 2001; 103:1245–1249. PMID: 11238268.

36. Mancia G, Facchetti R, Parati G, Zanchetti A. Visit-to-visit blood pressure variability, carotid atherosclerosis, and cardiovascular events in the European Lacidipine Study on Atherosclerosis. Circulation. 2012; 126:569–578. PMID: 22761453.

37. Musini VM, Wright JM. Factors affecting blood pressure variability: lessons learned from two systematic reviews of randomized controlled trials. PLoS One. 2009; 4:e5673. PMID: 19479061.

38. Mehlum MH, Liestol K, Kjeldsen SE, Julius S, Hua TA, Rothwell PM, Mancia G, Parati G, Weber MA, Berge E. Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks. Eur Heart J. 2018; 39:2243–2251. PMID: 29365085.

39. Krakoff LR. Fluctuation: does blood pressure variability matter. Circulation. 2012; 126:525–527. PMID: 22761455.

40. Wijsman LW, de Craen AJ, Muller M, Sabayan B, Stott D, Ford I, Trompet S, Jukema JW, Westendorp RG, Mooijaart SP. Blood pressure lowering medication, visit-to-visit blood pressure variability, and cognitive function in old age. Am J Hypertens. 2016; 29:311–318. PMID: 26156873.

41. Diaz KM, Veerabhadrappa P, Kashem MA, Feairheller DL, Sturgeon KM, Williamson ST, Crabbe DL, Brown MD. Relationship of visit-to-visit and ambulatory blood pressure variability to vascular function in African Americans. Hypertens Res. 2012; 35:55–61. PMID: 21814215.

42. Shimbo D, Shea S, McClelland RL, Viera AJ, Mann D, Newman J, Lima J, Polak JF, Psaty BM, Muntner P. Associations of aortic distensibility and arterial elasticity with long-term visit-to-visit blood pressure variability: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Hypertens. 2013; 26:896–902. PMID: 23537891.

43. Faramawi MF, Delongchamp R, Said Q, Jadhav S, Abouelenien S. Metabolic syndrome is associated with visit-to-visit systolic blood pressure variability in the US adults. Hypertens Res. 2014; 37:875–879. PMID: 24804612.

44. Su DF. Treatment of hypertension based on measurement of blood pressure variability: lessons from animal studies. Curr Opin Cardiol. 2006; 21:486–491. PMID: 16900013.

45. Song H, Wei F, Liu Z, Zhao Y, Ye L, Lu F, Zhang H, Diao Y, Qi Z, Xu J. Visit-to-visit variability in systolic blood pressure: correlated with the changes of arterial stiffness and myocardial perfusion in on-treated hypertensive patients. Clin Exp Hypertens. 2015; 37:63–69. PMID: 24678998.

46. Veloudi P, Sharman JE. Methodological factors affecting quantification of blood pressure variability: a scoping review. J Hypertens. 2018; 36:711–719. PMID: 29176390.