Idea Transcript
EDITOR’S
CHOICE
Management of Hypertension in Diabetes Mellitus Sidhartha Das*, Rina Mohanty**, UK Patnaik***
Management of hypertension in diabetics demands special attention, more so in Indian scenario. Higher prevalence of hypertension (HTN) amongst diabetics in India has been reported since 19851. Review on the subject by Das in 1995 (on Indian data) had revealed the prevalence to be as variable as 7 per cent in Cuttack to 30.9 per cent at Sevagram2. Further, there was a variable difference between IDDM (Type-1) and NIDDM (Type-2) i.e., 10 versus 32 per cent respectively in diabetics from Mumbai2. Recent studies from Manipal revealed about 40 per cent diabetics to be hypertensive3. Such higher prevalence of HTN could partly be due to better assessment in diabetics but most likely on par with change of lifestyle and increase in the prevalence of noncommunicable diseases in rapidly growing economies. Consequently, cardiovascular diseases in diabetics will account for 5 to 20 per cent of the total health care expenditure. A number of modifiable arterial risk factors contribute to the higher prevalence of cardiovascular disease (CVD) in patients with diabetes mellitus (DM) 4. HTN is one of the modifiable arterial risk factors for developing CVD. Its management is not always easy and published evidence suggests that failure of clinical management is not uncommon. It is therefore necessary that specific guidelines be laid down for the treatment of HTN in Indian patients with DM. * Addl. Professor & Unit Head PG Department of Medicine ** Asst. Professor PG Department of Medicine *** Asst. Professor Department of Cardiology SCB Medical College & Hospital, Cuttack-753 007.
Types of hypertension in diabetes mellitus 2 1. Essential hypertension 2. Hypertension consequent to nephropathy 3. Isolated systolic hypertension 4. Supine hypertension with orthostatic fall
Possible mechanisms in pathogenesis2 A. Uncontrolled metabolic state B. Insulin resistance leading to abnormalities in : i ii iii iv v vi vii viii ix
Renal tubular ion exchange. Transmembrane ion exchange in vascular bed. Renin angiotensin system. Prostaglandin kallikrein/kinin system. Inter-relationship with Mg. Atrial natriuretic peptide. Diabetic nephropathy. Sympathetic nervous system involvement. Other endocrine syndromes/secondary causes.
Guidelines for the management of HTN Despite the fact that patients who suffer from both DM and HTN could represent a complex entity as regards developing CVD, short comments have been made in the JNC VI report on the treatment of HTN in diabetic subjects 5. In view of the importance of the problem the issue needs to be discussed under three specific areas, viz.: 1. Which measurement of arterial blood pressure should be considered? 2. Which arterial pressure target value should be considered? 3. Which treatment modalities should be proposed as an optimal strategy?
Measurement of arterial blood pressure
use the higher category amongst the two for management.
HTN is defined as systolic blood pressure (SBP) of 140 mmHg or greater and/or diastolic blood pressure (DBP) of 90 mmHg or greater5. The object of identifying and treating high blood pressure is to reduce the risk of CVD and associated morbidity and mortality. It is therefore imperative to provide a classification of blood pressure in adults so as to identify the high risk individuals and to provide guidelines for treatment and followup.
Supine, sitting, and standing blood pressure should be measured in all diabetic subjects5. This is an important issue in diabetic patients where autonomic neuropathy often leads to supine HTN with postural fall of blood pressure. Arterial blood pressure measured in the sitting position should be considered as ideal4.
Systolic and diastolic pressure target values The important question is : To which level should the blood pressure be reduced in a diabetic hypertensive patient? This has not been clearly answered, even though arguments for a lower target blood pressure for diabetics has been recommended6. There is no specific guideline on the exact values for HTN control in diabetics. In several official recommendations, a definition is given as to what is meant by optimum, fair, acceptable, or poor control keeping in view the population under consideration. The necessary details are given in Table-II.
Table I : Classification of blood pressure for adults (JNC VI report) Category
Systolic BP (mmHg)
Diastolic BP (mmHg)
Optimal Normal High normal Hypertension Stage 1 Stage 2 Stage 3
< 120 < 130 130-139
and < 80 and < 85 or 85-89
140-159 160-179 equal/above 180
or 90-99 or 100-109 or above 100
Where SBP and DBP fall into different categories,
Table II : Targets for HTN control in diabetic subjects belonging to various geo-ethnic origin. A.
References regarding guidelines in diabetics (general recommendation)
Optimal
in mmHg Fair/Acceptable
Poor
European NIDDM policy group Asian-Pacific NIDDM Policy group8 European IDDM Policy group9 Canadian Diabetes Advisory Board10 WHO Diabetes guidelines11
≤ 140/90 - do ≤ 140/85 ≤ 140/90 a ≤ 140/85
≤ 160/95 - do – < 150/90 –
> 160/90 > 160/95 – > 150/90 –
Specific guidelines on HTN in diabetics United Kingdom working party12 Canadian Consensus Conference13 ADA Consensus Statement14 ALFEDIAM recommendations15
< 140/95 < ?/90 < 130/85 c 160/90
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B.
a : In absence of nephropathy, otherwise ≤ 135/85 mmHg. b : Not enough evidence to recommend a target value for SBP in patients with microalbuminuria. It may be worth attempting to achieve a DBP of approximately 80 mmHg. c : Similar to recommendations by the National High Blood Pressure Education Program Working Group16 and the JNC VI5. d : In the absence of nephropathy, otherwise ≤ 140/80 mmHg.
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It is worth noting that in a subgroup of 1,501 patients with DM, in the Hypertension Optimal Treatment (HOT) study, the risk of major cardiovascular events was halved in the group randomised to a DBP ≤ 80 mmHg when compared with the target group with DBP < 90 mmHg17. It was concluded that active lowering of blood pressure was particularly beneficial in the subgroup arguments for recommending a reduction of DBP to values of 80 mmHg or below in diabetic subjects.
Antihypertensive treatment guidelines In diabetic patients, particularly those with mild to moderate HTN, the first line of treatment includes lifestyle modification, i.e., weight control, low fat anti-atherogenic diet, salt restriction, reduction in alcohol intake, discontinuation of smoking, and supervised regimens of physical activity. The next step would be administration of antihypertensive drugs. Five classes of drugs are considered to be effective for monotherapy. Diuretics, beta-blockers, calcium channel blocker, alpha 1 adrenergic blockers, ACE-inhibitors, and likely angiotensin-receptor antagonists are the armamentarium of first line drugs available for use in India. In the absence of randomised controlled large scale clinical trials on the various classes of antihypertensive agents in diabetic patients with HTN, the choice of treatment is based on our understanding of the pathophysiology of HTN in diabetics and known pharmacological action as well as side-effects of the drug to be administered. Antihypertensive medications should not adversely affect carbohydrate and lipid metabolism. Keeping in view the likely reason for HTN in a diabetic, any of the above-mentioned group of drugs can be used. However, the therapeutic implications have to take into consideration the existence/ absence of any concurrent disease/complication viz., IHD, CHF, Nephropathy, PVD. Then the issue to be considered is the efficacy, tolerance, safety and, in India, the cost effectiveness of the drug
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for the patient under consideration. For such reasons, central adrenergic antihypertensives are not considered to be of first choice. According to the European NIDDM Policy Guidelines, thiazides may be used in small doses and low doses of cardioselective beta-blockers are to be preferred in order to avoid metabolic interference7. The ALFEDIAM guidelines consider beta-blockers to be useful antihypertensive agent in diabetics with coronary artery disease, while alpha 1 adrenergic blockers were not taken into account15. On the other hand, potentially favourable effects of alpha 1 blockers on the lipid profile makes them the first line therapy in the ADA statement14. These drugs, in addition to HTN also reduce insulin resistance without influencing glucose metabolism. Despite numerous guidelines, none give precise indications of a first choice drug for treatment or the best pharmacological combination. This requires appropriate attention as a high percentage of diabetics are not controlled, with regards to HTN, with monotherapy. It has long been understood that the choice of antihypertensive drugs in diabetic patients with incipient nephropathy should be an ACE-inhibitor. ACE-inhibitors also prolong bradykinin action which potentiates insulin induced glucose uptake and therefore enhance insulin sensitivity. However, diabetics with rising azotaemia, i.e., serum creatinine value above 2.5 mg/dl should not be given ACE-inhibitor as it may lead to hyperkalaemia and complications. If the target blood pressure of 130/85 is not achieved with the use of ACE-inhibitor alone, addition of low dose diuretic is recommended18. Interestingly the nephroprotective effect of ACEinhibitor may be expected even in microalbuminuric normotensive patients with Type1 DM. However, the UKPDS study group comparing the efficacy of atenolol with captopril in reducing the risk of macrovascular and microvascular complications in Type-2 diabetics (vast majority of Indian diabetics are Type-2) did not observe any difference in such end points19. Moreso, urinary albumin excretion was reduced
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to a similar extent in both the groups of diabetics. This study did not provide evidence that either drug had any specific beneficial or deleterious effect and leads to the conclusion that control of HTN itself may be more important than the treatment used. In diabetics with isolated systolic HTN, diuretics are of greater benefit. Natriuretic calcium-channel blockers like nitrendipine may be more suitable for diabetics with systolic HTN and mild diastolic HTN.
Conclusion The guidelines for management of HTN in diabetics offered in this article are on evidence based consensus and it seems that a more strict control of HTN is required in diabetics as compared to nondiabetic hypertensives. While the drug of first choice to lower HTN in a diabetic is often decided to a larger extent by the presence or absence of other metabolic/vascular complications, as per the UKPDS results, control of HTN and maintainance of ideal blood pressure is the moot point that would benefit the diabetic patient most.
References 1.
Patel JC. Diabetes and its complications. J Diab Assn Ind 1985; 25: 16-25.
2.
Das S. Etiopathogenesis of hypertension in diabetes mellitus. Int J Diab Dev Count 1995; 15: 106-09.
3.
Rau NR, Acharya RV, Shah S. Incidence of diabetic complications in newly detected cases of NIDDM. Nova Nordisk Diabetes Update Proceedings 1999, Helath Care Communications, Bangalore 1999; 35-6.
4.
Kumar A. Indian scenario – hypertension. In : Das S Ed. Complications of Diabetes in Indian Secnario, proceedings Vol. 1. USV Ltd. Mumbai 2000.
5.
The Sixth Report of the Joint National Committee on Prevention, Detection, Education and treatment of High Blood Pressure. Arch Int Med 1997; 157: 2413-46.
6.
Ruilope LM, Garcia-Robles R. How far should blood pressure be reduced in diabetic hypertensive patients? J
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Hypertension 1997; 15 (Suppl 2): S63-5. 7.
Albert KGMM, Gries FA, Jervell J et al. For the Europian NIDDM Policy Group, A desktop guide for the management of non-insulin-dependent diabetes mellitus (NIDDM): an update. Diab Med 1994; 15: 899-909.
8. Asian-Pacific NIDDM Policy Group. Non-insulin dependent diabetes mellitus (NIDDM). Practical targets and treatments. Sydney : Health Communications, Australia, 1995. 9. European IDDM Policy Group 1993. Consensus guidelines for the management of insulin-dependent (Type-I) diabetes mellitus. Diab Med 1993; 10: 9901005. 10. Expert Committee of the Canadian Diabetes Advisory Board. Clinical practice guidelines for treatment of diabetes mellitus. 11. World Health Organisation. Management of diabetes mellitus. Standards of care clinical practice guidelines. Diabetes prevention and control. WHO-EM/DIA/6/E/G. Geneva : World Health Organisation 1994; 27-9. 12. A Working Party (UK). Blood pressure and diabetes : Everyone’s concern. Clineham : RR Assoc 1994. 13. Dawson KG, KcKenzie JK, Ross SA et al. Report of the Canadian Hypertension Society Consensus Conference: 5. Hypertension and Diabetes. Can Med Assoc J 1993; 149: 821-6. 14. ADA Consensus Statement. Treatment of hypertension in diabetes. Diab Care 1996; 19: S107-13. 15. Bauducean B, Chatellier G, Cardonnier D et al. Recommendations de 1’ALFEDIAM. Hypertension et diabete. Diabete Metabol 1996; 22: 64-76. 16. National High Blood Pressure Education Program Working Group. Report on hypertension in diabetes. Hypertension 1994; 23: 145-58. 17. 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) randomised trial. Lancet 1998; 351: 1766-72. 18. Bennett PH, Haffner S, Kasiske BL et al. Screening and management of microalbuminuria in patients with diabetes mellitus : Recommendations to the Scientific Advisory Board of the National Kidney Foundation from an Ad Hoc Committee of the Council on Diabetes Mellitus of the National Kidney Foundation. Am J Kidney Dis 1995; 25: 107-12. 19. UK Prospective Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes : UKPDS 39. Br Med J 1998; 317: 713-20.
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