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Prof. Guido Grassi
Guidelines on diabetes, pre-diabetes and cardiovascular disease recently published by the European Society of Cardiovascular/European Association for the Study of Diabetes (ESC/EASD) (1) pay special attention to epidemiological and pathophysiological issues related to hypertension in diabetic patients. They also provide a number of recommendations on the impact of these two diseases on cardiovascular risk as well as on the blood pressure targets of antihypertensive treatment.
In the context of the ESC/EASD Guidelines on diabetes, pre-diabetes and cardiovascular disease, the clinical impact of the association of diabetes and hypertension as well as its therapeutic implications have been extensively reviewed and critically commented (1). All these issues will be summarised in this article.
The prevalence of high blood pressure is up to three time greater in diabetic versus in non-diabetic patients, presumably because being overweight, obesity and renal dysfunction (which are of frequent detection in the diabetic patient) favour the development and progression of the hypertensive state. When diabetes and hypertension coexist, there are exponential detrimental effects on the cardiovascular risk, due to the occurrence of endothelial dysfunction, micro- and macrovascular complications as well as blood pressure elevation. This triggers the development of left ventricular hypertrophy, myocardial ischaemia and congestive heart failure. The epidemiological “burden” of the above mentioned cardiovascular complications can be quantified as follows. The risk for coronary heart disease increases by 1.7 fold to 1.9 fold in type 1 and type 2 diabetes mellitus patients with high blood pressure as compared to non-diabetic patients (2). As far as left ventricular dysfunction and heart failure is concerned the estimated risks are even greater (taking into account that in the Framingham study the relative risk for clinical heart failure in diabetics patients increases by 4.0 fold as compared to non-diabetics) (3). Finally, according to the Finnish Prospective Study (4), the stroke risk is increased 3 to 4 fold in hypertensive patients with diabetic disease.
In type 1 and type 2 diabetic hypertensive patients, antihypertensive drug treatment should be particularly aggressive and aimed at lowering blood pressure below 130/80 mmHg. This target of treatment is based on the evidence, collected in the United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) study, that an intensive blood pressure reduction in hypertensive patients is associated with a low rate of cardiovascular events (5,6). A blood pressure reduction below 130/80 mmHg (ideally less than 120/75 mmHg) should be clinically relevant in diabetic patients with proteinuria, reduced glomerular filtration rate or overt nephropathy. Unfortunately, in current clinical practice many patients with diabetes and hypertension, despite treatment, fail to achieve the above mentioned recommended targets (7).
In diabetic hypertensive patients, the antihypertensive therapeutic approach should be aimed at: • Reducing elevated blood pressure values. • Improving renal and cardiovascular protection. • Lowering elevated cardiovascular risk profiles.
The large number of clinical trials performed so far in diabetic hypertensive patients have shown that the benefits related to antihypertensive treatment mainly depend on the blood pressure control “per se”. However, some drugs (particularly those acting on the renin-angiotensin system) may have more favourable effects than others, particularly when renal damage coexists. Greater cardiovascular protection can be obtained by employing combination treatment, with the use of drugs interfering with the renin-angiotensin system, which appears to be actively involved in the development and/or progression of end organ damage. It should be made clear, however, that except for a few specific indications, any antihypertensive drug or drug combination can be used, unless contraindicated, since achieving blood pressure goals seem more important than selecting a specific blood pressure lowering compound.
Clinical evidence has shown that in diabetic hypertensives, strict glycaemic control is as important as a tight blood pressure control. This means that metabolic intervention should be aimed at lowering fasting glucose levels below 108 mg/dl and glycated haemoglobin to ? 6.5 % or below. Given the high risk profile of the patients combining diabetes and hypertension, the total cholesterol and HDL cholesterol targets should be <175 mg/dl and >40 mg/dl (> 46 mg/dl for women), respectively. A further therapeutic intervention aimed at preventing coronary and cerebrovascular events should be represented by antiplatelet drugs (aspirin).
The clustering of risk factors represented by hypertension, hyperglycaemia (ranging from impaired fasting glucose to overt diabetes), dyslipidaemia and visceral obesity termed metabolic syndrome is of frequent detection in current clinical practice and represents a high risk condition for cardiovascular complications.
The key message coming out from the ESC/EASD Guidelines is that this condition requires early diagnosis and an aggressive treatment (1). The target blood pressure values are those previously mentioned for the hypertensive diabetic patients with signs of renal damage. Finally, ESC/EASD Guidelines emphasise the not infrequent association of hypertension (particularly when complicated by diabetes) and atrial fibrillation (1). They also underline the adverse clinical impact of this association, given that the evidence that atrial fibrillation represents one of the most important risk factors for stroke (8). Also in the case of this comorbidity, the ESC/EASD Guidelines provide recommendations based on early diagnosis and rigorous therapeutic approach based on antithrombotic and anticoagulant therapy.
The Guidelines document also reviews the evidence that some metabolic actions of various blood pressure lowering drugs may favour new onset diabetes. This has been particularly shown for beta-blockers and diuretics, while ACE-inhibitors and angiotensin II receptor blockers may be devoid of such an effect.(9). Beta blockers and diuretics should not be used or only with great caution in hypertensive patients with metabolic syndrome or impaired fasting glucose. However, in the case of a hypertensive patient with established diabetes they can remain as part of the therapeutic armamentarium aimed at effectively controlling blood pressure values. ESC/EASD RECOMMENDATIONS ON ANTIHYPERTENSIVE TREATMENT IN DIABETES-RELATED HYPERTENSION.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Ryden L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007;28:88-136. 2. Pyörälä K, Lehto S, De Bacquer D et al., on behalf of the EUROASPIRE I II Group. Risk factor management in diabetic and non diabetic coronary heart disease patients. Findings from heart disease patients from EUROASPIRE I and II surveys. Diabetologia 2004;47:1257-1265. 3. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974;34:29-34. 4. Hu G, Sarti C, Jousilahti P, et al. The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality. Stroke. 2005 Dec;36(12):2538-43. 5. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703–713. 6. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) Trial. Lancet 1998;351:1755–1762. 7. Mancia G, Grassi G. Systolic and diastolic blood pressure control in antihypertensive drug trials. J Hypertens. 2002;20:1461-1464 8. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449–1457. 9. Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens 2006;24:3-10.
Prof. G. Grassi Milan, Italy Past-Chairman of the ESC Working Group on Hypertension and the Heart.
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