Effect of tight control of HbA1c and blood pressure on cardiovascular diseases in type 2 diabetes: An observational study from the Swedish National Diabetes Register (NDR)

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Abstract

Aim

To estimate hazard ratio (HR) of first incident fatal/non-fatal cardiovascular diseases (CVD) in female/male type 2 diabetic patients, with tight versus adverse control of HbA1c and blood pressure (BP) at baseline, age 30–70 years, no baseline CVD, followed for mean 5.7 years.

Methods

2593 patients with tight control of HbA1c <7.5% and BP ≤140/90 mmHg (median 6.5%/130/80 mmHg), and 2160 patients with adverse control 7.5–9.0%/141–190/91–110 mmHg (median 8.1%/155/85 mmHg).

Results

The hazard ratio (HR) for CVD with tight/adverse control was 0.67 (0.55–0.80; p < 0.001), adjusting for age, sex, duration, hypoglycaemic treatment, smoking, BMI, lipid-lowering drugs, antihypertensive drugs, microalbuminuria. Adjusted HR for myocardial infarction, coronary heart disease, stroke and total mortality were 0.72 (0.56–0.92; p = 0.01), 0.69 (0.55–0.86; p < 0.001), 0.62 (0.45–0.84; p < 0.001), 1.00 (0.72–1.39). The partial population-attributable risk percent for myocardial infarction, stroke and CVD was 23%, 33%, 29% if adverse HbA1c/BP control could be avoided, while 43%, 38%, 39% with overweight and smoking also avoided. Baseline lower BMI and absence of microalbuminuria were associated with tight control.

Conclusion

Median difference of HbA1c/BP 1.6%/25/5 mmHg between tight and adverse control considerably reduced the risk of cardiovascular diseases. The findings call for a multi-factorial approach to improve HbA1c, BP, obesity, smoking, and microalbuminuria.

Introduction

Hypertension is a well-established risk factor for micro- and macrovascular complications in type 2 diabetic patients. An observational analysis in the UKPDS [1] has demonstrated a linear relationship between mean in-study systolic blood pressure (BP) and the risk of cardiovascular disease (CVD). Tight BP control in hypertensive type 2 diabetic patients, and several antihypertensive drug classes versus placebo, have been documented to reduce the risk of both micro- and macrovascular disease, in the UKPDS [2], [3] as well as in several other intervention studies [4], [5], [6], [7]. A positive association between HbA1c and risk of micro- and macrovascular complications in type 2 diabetic patients has also been shown in previous epidemiological studies [2], [8], [9], [10] and a meta-analysis [11]. It is well established that improved glycaemic control reduces the risk of microvascular complications in both type 1 and type 2 diabetes [12], [13], while the role of glycaemic control in reducing the risk of macrovascular disease is less clear.

UKPDS has shown that tight control of HbA1c is beneficial with regard to CVD risk during 10 years of post-trial follow-up [14], while the ACCORD [15], ADVANCE [16] and VADT [17] trials have not been able to confirm the beneficial effect of tight HbA1c control on CVD risk. Further studies analysing the effect of tight control of both HbA1c and BP, and analysis of predictors for a tight control, should be of value. The convincing results of the long-term follow-up in the Steno-2 study of type 2 diabetic patients with microalbuminuria have also underlined the importance of concomitant treatment of multiple cardiovascular risk factors [18].

At this background, this observational study in type 2 diabetic patients was carried out with the aim to analyse the effect of baseline tight control of HbA1c and BP, compared to adverse control, on the risk of cardiovascular diseases, and also with the aim to analyse the association between baseline clinical characteristics and tight control.

Section snippets

Material and methods

The NDR was launched in 1996 as part of the Swedish implementation of the principles of the St. Vincent declaration on quality in diabetes care, with reports of patient data nationwide, and offers a unique possibility to survey the treatment and risk factor control in diabetic patients in everyday clinical practice. Reporting to the NDR is based on information collected at least once a year during patient visits at hospital outpatient clinics and primary health care clinics all over Sweden, and

Baseline data

Baseline clinical characteristics and risk factors are shown in Table 1, in 2593 patients with tight control of HbA1c <7.5% and BP ≤140/90 mmHg, and in 2160 patients with adverse control of HbA1c 7.5–9.0% and BP 141–190/91–100 mmHg. Median HbA1c and BP were 6.5% and 130/80 mmHg with tight control and 8.1% and 155/85 mmHg with adverse control, a difference of 1.6% and 25/5 mmHg. The frequency of hypertension (treated with antihypertensive drugs or untreated with BP >130/80 mmHg) was around 80% and

Discussion

This observational study has shown that female and male type 2 diabetic patients followed for 6 years, with baseline more tight control of HbA1c <7.5% and BP ≤140/90 mmHg (median HbA1c and BP 6.5% and 130/80 mmHg, around 80% hypertensive patients), compared to those with adverse HbA1c and BP control (median HbA1c and BP 8.1% and 155/85 mmHg, all hypertensive patients), had a 33% lower risk of fatal/non-fatal CVD, 31% lower risk of fatal/non-fatal CHD, and 38% lower risk of fatal/non-fatal stroke,

Conflict of interest

There were no conflicts of interest.

Acknowledgements

The NDR Working Group consists of Soffia Gudbjörnsdottir (national coordinator), Jan Cederholm, Björn Eliasson, Peter M. Nilsson, Björn Zethelius and Katarina Eeg-Olofsson. We thank the regional NDR coordinators, all participating nurses, physicians, and other staff members who have contributed to the study. We also thank the patients with diabetes who, both individually and collectively, through their patient organization, the Swedish Diabetes Federation, support the NDR. The Swedish Board of

References (38)

  • H.C. Gerstein et al.

    The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis

    Diabetologia

    (2005)
  • I.M. Stratton et al.

    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

    BMJ

    (2000)
  • E. Selvin et al.

    Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus

    Ann. Intern. Med.

    (2004)
  • The Diabetes Control and Complications Trial Research Group

    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

    N. Engl. J. Med.

    (1993)
  • UK Prospective Diabetes Study (UKPDS) Group

    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

    Lancet

    (1998)
  • R.R. Holman et al.

    10-year follow-up of intensive glucose control in type 2 diabetes

    N. Engl. J. Med.

    (2008)
  • H.C. Gerstein et al.

    Effects of intensive glucose lowering in type 2 diabetes

    N. Engl. J. Med.

    (2008)
  • A. Patel et al.

    Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes

    N. Engl. J. Med.

    (2008)
  • W. Duckworth et al.

    Glucose control and vascular complications in veterans with Type 2 diabetes

    N. Engl. J. Med.

    (2009)
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