Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR)

doi:10.1016/j.diabet.2009.04.010

Diabetes & Metabolism

Volume 35, Issue 6, December 2009, Pages 439-446

https://doi.org/10.1016/j.diabet.2009.04.010 Get rights and content

Abstract

Objectives

To analyze pulse pressure (PP) as a risk predictor for coronary heart disease (CHD), stroke and cardiovascular disease (CVD; CHD and/or stroke) in type 2 diabetic patients.

Methods

A total of 11,128 female and male type 2 diabetic patients with known baseline PP values and no CVD, aged 50–74 years, were followed for a mean duration of 5.6 years (1998–2003). A subgroup of 5521 patients with known mean PP values (mean values at baseline and at the end of the study) was also included.

Results

Hazard ratios (HRs) with 95% CI for fatal/nonfatal CHD with baseline or mean PP ≥ 75 mmHg, compared to < 75 mmHg, were 1.23 (1.07–1.40; P = 0.003) and 1.32 (1.07–1.62; P = 0.009), respectively, after adjusting for mean blood pressure (MBP), age, gender, diabetes duration, HbA_1c, body mass index (BMI), lipid-reducing drugs, microalbuminuria > 20 μg/min, antihypertensive drugs and hypoglycaemic treatment, using Cox regression analyses. Fully-adjusted respective HRs for stroke were 1.17 (0.98–1.39) and 1.21 (0.90–1.61) and, for CVD, 1.23 (1.10–1.37; P < 0.001) and 1.28 (1.07–1.52; P = 0.007). Fully-adjusted HRs for baseline PP increased per quartile and, CHD, stroke or CVD, were 1.09 (1.03–1.16; P = 0.004), 1.14 (1.05–1.23; P = 0.002) and 1.11 (1.05–1.17; P < 0.001), respectively. The data suggest that, if a mean PP ≥ 75 mmHg were to be avoided, then 15% and 17% of CHD and or CVD, cases, respectively, in such a cohort might be prevented after multivariable adjustments, with a further 10% of cases avoided if also adjusted for MBP and age. Increasing baseline MBP, age and microalbuminuria were independently and significantly associated (P < 0.001) with increasing baseline or mean PP.

Conclusion

Increased PP is a powerful independent risk predictor of CVD in type 2 diabetic patients, and lowering PP can lead to a marked reduction in risk.

Résumé

Objectifs

Évaluer la valeur de la pression pulsée (PP) comme un facteur de risque d’événements coronaires (EC), d’accidents vasculaires cérébraux ischémiques (AVC) et d’événements cardiovasculaires (ECV : EC et/ou AVC) mortels et non mortels chez des diabétiques de type 2 (DT2).

Méthodes

Onze mille cent vingt-huit patients des deux sexes atteints de DT2, dont la PP basale (PPB) avait été déterminée (âge 50–74 ans, absence d’antécédents CV à l’inclusion) ont été suivis en moyenne 5,6 ans (1998–2003). Chez 5521 d’entre eux, la pression pulsée moyenne (PPM) (moyenne de la PP à l’inclusion et en fin d’étude) était enregistrée.

Résultats

En analyse multivariée par régression de Cox, le risque relatif (RR) (intervalle de confiance à 95 %) d’événements coronaires chez les patients dont la PPB ou la PPM était supérieure ou égale à 75 mmHg, comparés à ceux dont les valeurs étaient inférieure à 75 mmHg, était respectivement de 1,23 (1,07–1,40 ; P = 0,003) et 1,32 (1,07–1,62 ; P = 0,009), après ajustement pour la pression artérielle moyenne (PAM), l’âge, le sexe, la durée de diabète, l’HbA_1c, l’IMC, la prise d’hypocholestérolémiants, d’antihypertenseurs, l’existence d’une micro-albuminurie supérieure à 20 μg/min et le traitement hypoglycémiant. Le RR multi-ajusté d’accident vasculaire cérébral était respectivement de 1,17 (0,98–1,39) et de 1,21 (0,90–1,61), et celui d’événement cardiovasculaire de 1,23 (1,10–1,37 ; P < 0,001) et 1,28 (1,07–1,52 ; P = 0,007). L’augmentation du RR multi-ajusté d’événements coronaires, d’accidents vasculaires cérébraux et d’événements cardiovasculaires totaux par quartile de la PPB était respectivement de 1,09 (1,03–1,16 ; P = 0,004), 1,14 (1,05–1,23 ; P = 0,002) et 1,11 (1,05–1,17 ; P < 0,001). S’il avait été possible d’obtenir à l’inclusion une PPB inférieure à 75 mmHg, après ajustement multivarié, 15 % des événements coronaires et 17 % des accidents vasculaires cérébraux de la cohorte auraient pu être évités (10 % des événements après ajustement supplémentaire pour la PAM et l’âge). L’augmentation de la PAM et de l’âge, ainsi que la micro-albuminurie basale étaient associées de manière indépendante (P < 0,001) à la PPB et à la PPM.

Conclusion

L’augmentation de la PP est un facteur de risque d’événements cardiovasculaires puissant et indépendant chez des diabétiques de type 2. Une réduction de la PP permettrait une réduction de ce risque.

Introduction

Patients with type 2 diabetes have a two- to four-fold higher risk of cardiovascular disease (CVD) than do nondiabetic, healthy subjects [1], [2]. The importance of systolic blood pressure (BP) as a risk factor for cardiovascular events has been verified by the United Kingdom Prospective Diabetes Study (UKPDS), and strict BP control has proved effective in reducing the risk of stroke and diabetes-related mortality [3]. Such patients are also thought to have increased arterial rigidity [4], [5], [6], [7], [8], and pulse pressure may be regarded as an indirect measure of arterial stiffness in middle-aged and older subjects [4], [9], [10], [11]. However, only a few studies have investigated the predictive value of pulse pressure as a risk factor for CVD in patients with type 2 diabetes [12], [13].

The aim of this observational prospective study was to analyze the association between pulse pressure, coronary heart disease (CHD), stroke and CVD (CHD and/or stroke) in a large sample of type 2 diabetic patients from the Swedish diabetes population registered at primary-care centers and hospital diabetes clinics nationwide.

Section snippets

The Swedish National Diabetes Register (NDR)

The Swedish National Diabetes Register (NDR) was initiated in 1996 as a tool for local quality assurance in diabetes care. Annual reporting to the NDR is carried out by trained physicians and nurses via the Internet and through databases of clinical records, comprising information collected during patient visits at hospital outpatients clinics and primary healthcare centers across Sweden, from approximately 200 units participating in the present study. All included patients gave their informed

Results

Table 3 shows the baseline characteristics of the study sample of 11,128 men and women with type 2 diabetes, aged 50–74 years and free of CVD at baseline, divided into subgroups according to baseline pulse pressure ≥ 75 mmHg or < 75 mmHg, as 75 mmHg corresponded to the 75th percentile in the distribution of baseline pulse pressure. Those with a baseline pulse pressure ≥ 75 mmHg were older, had higher MBP and more microalbuminuria, and 60% were treated with antihypertensive drugs. Mean values of

Discussion

The main finding of this large-scale, observational, prospective study of type 2 diabetic patients was that elevated pulse pressure is a strong risk predictor of fatal/nonfatal CHD, stroke and CVD, independent of other cardiovascular risk factors and clinical characteristics. Furthermore, if elevated pulse pressure could be avoided in such a cohort, then 15–17% of all cases of CVD might be prevented independent of other risk factors, and 10% might be prevented after also adjusting for age and

Conflicts of interest

The authors have no conflicts of interest to declare.

Acknowledgements

We would like to thank the regional NDR coordinators, and all participating nurses, physicians and other staff who have contributed to the NDR. Most of all, we wish to thank the patients who support the NDR, both individually and collectively, through their patient organization, the Swedish Diabetes Federation. The Swedish Association of Local Authorities and Regions and the Swedish Society of Diabetology jointly fund the NDR.

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Abstract

Objectives

Methods

Results

Conclusion

Résumé

Objectifs

Méthodes

Résultats

Conclusion

Introduction

Section snippets

The Swedish National Diabetes Register (NDR)

Results

Discussion

Conflicts of interest

Acknowledgements

Am J Cardiol

Am J Cardiol

Am J Hypertens

J Am Coll Cardiol

Am J Med

J Am Coll Cardiol

Kidney Int.

Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction

N Engl J Med

Diabetes, other risk factors, and 12 year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial (MRFIT)

Diabetes Care

Tight blood pressure control and risk of macrovascular and microvascular complications in type II diabetes: UKPDS 38

BMJ

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease

Diabetologia

Diabetes mellitus and renal failure: effects on large artery stiffness

J Hum Hypertens

Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study

Hypertension

Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension

J Hypertens

Vascular stiffness and arterial compliance. Implications for Systolic Blood Pressure

Am J Hypertens

Determinants of increasing pulse pressure during 23 years’ follow-up as a marker of arterial stiffness and vascular ageing

Blood Press

Diabetes, pulse pressure and cardiovascular mortality: the Hoorn Study

J Hypertens

The National Diabetes Register in Sweden: An implementation of the St. Vincent Declaration for Quality Improvement in Diabetes Care

Diabetes Care

Hypertension in diabetes – trends in control and relation to macrovascular morbidity in repeated national surveys from Sweden

J Hum Hypertens

The gap between guidelines and reality: type 2 diabetes in a national diabetes register 1996–2003

Diabet Med