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Treatment of Hypertension in Diabetes

CHAPTER TWO

2.12 Hypertension in Diabetes

2.12.5 Treatment of Hypertension in Diabetes

The goal of treatment in hypertensive diabetics is to maintain the blood pressure at levels below 130/75mmHg13. This target has been adopted by many authorities notably the British Hypertension Society. In the Hypertension Optimal Treatment (HOT) study the optimum blood pressure for reduction of major cardiovascular events was found to be 139/83mmHg in non-diabetics and lower in patients with diabetes 13. In patients with hypertension and microalbuminuria, blood pressure

treatment with an angiotensin converting enzyme (ACE) inhibitor delays progression to overt nephropathy.

Two treatment modalities are employed, non-pharmacological and pharmacological approach.

2.12.5.1 Nonpharmacological Therapy

Appropriate lifestyle measures (health promoting lifestyle modification) may remove the need for drug therapy in patients with prehypertension and stage 1 hypertension, reduce the dose and /or the number of drugs required in patients with established hypertension, and directly reduce cardiovascular risk 60,62,63,64.

Correcting obesity, reducing alcohol intake, restricting salt intake to 70-90mmol/day, taking regular physical exercise, and consumption of fruits, vegetables and high fibre, low salt, low saturated fat diets (DASH-dietary approaches to stop hypertension) have been shown to lower blood pressure 63. The maximum daily alcohol consumption for males should not exceed three units (30g) and in women, two units (20g) 63. In addition, all diabetic patients should quit smoking 61. Patients need a lot of motivation to achieve these and require regular and sustained counseling with active involvement and support of the spouse and family members.

2.12.5.2 Pharmacological Therapy Antihypertensive Drugs

Antihypertensive agents should be selected based on the advantages and disadvantages of the therapeutic agent in the context of individual patient’s risk profile. Antihypertensives currently in use for treatment in diabetics include ACE

inhibitors (ACEIs), Angiotensin II receptor blockers (ARBs), Calcium channel blockers (CCBs), Diuretics, & adrenergic and Beta blockers (BBs), Vasodilators and Central adrenergic blockers.

ACEIs, ARBs, CCBs, and thiazide-like diuretics have shown benefit in reducing the incidence of cardiovascular disease in diabetic patients; thus, JNC 7 recommends ACEIs as first-line agents and the others as alternate agents. The diabetes-related considerations of anti-hypertensive agents are shown in table 2 below.

Table 2: Antihypertensives and there DM-Related Considerations

DRUG ADVANTAGES DISADVANTAGES

ACE Inhibitors

* Lisinopril

* Ramipril

* Captopril

* Enalapril

Glucose and lipid neutral and thus positively impact the cardiovascular risk profile. May improve insulin resistance May reduce LDL and increase HDL Diminish proteinuria and stabilize renal function.

Contraindicated in pregnant diabetics-and-those

anticipating pregnancy, renal artery stenosis, severe renal impairment and elderly

ARBS

* Losartan

* Valsartan

Similar to the above

Calcuim-channel blockers

* Nifedipine

* Amlodipine

* Felodipine

Glucose and lipid neutral;

May reduce cardiovascular morbidity and mortality in type 2 DM, particularly in elderly patients with systolic hypertension

Central Adrenergic blockers

* methyldopa

Lipid and glucose neutral Postural hypertension Impotence

DRUG ADVANTAGES DISADVANTAGES Thiazide diuretics

*Hydrochlothiazide

Very-effective-antihypertensive agents in blacks

May increase insulin resistance.

May negatively impact lipid profile.

Slightly increased risk of developing type 2 DM.

Impotence Beta blockers

(cardioselective)

* Atenolol

* Metoprolol Non-selective

* Propanolol

Effective agents Aggravating

hypoglycaemic events is rare when cardioselective (B1) agents are used.

Same as in thiazide diuretics

Vasodilators

* Hydralazine Lipid and glucose neutral Alpha-adrenergic

blockers

* Prazosin

* Doxazosin

May improve insulin resistance and positively impact lipid profile

Orthostatic hypotension especially in diabetics with autonomic neuropathy ...table developed by author (unpublished)

If microalbuminuria or overt albuminuria is present, the optimal antihypertensive agent is an ACE Inhibitor. ACE inhibitors improve intrarenal hemodynamics with decreased glomerular efferent arteriolar resistance and a resulting reduction of intraglomerular capillary pressure 70. If albumin excretion is normal, then an ACE Inhibitor or alternate agents may be used preferably low dose diuretics, calcium channel blocker or beta-blocker. At occasions, more than one or multiple antihypertensives may be required to achieve the optimal blood pressure goal of

<130/75mmHg13. There is no specific time limit to modify antihypertensive therapy or graduate from one to two to three drug therapy.

Usually lifestyle modifications; high unrefined carbohydrate, high-fibre, low saturated fat and low sodium diets may be the initial treatment of the diabetic with mild hypertension. Poor response over a period of two to three months or presence of any cardiovascular complication or micro-albuminuria warrants commencement of drug therapy. Drug of choice should be based on the outline above and also considering their side effects. Addition of second or third antihypertensive depends on response to the above and severity of hypertension at initial diagnosis. Ultimately, the aim is to reduce cardiovascular risk, prevent or suppress progression to nephropathy and maintain the blood pressure at levels below 130/75mmHg.

Other Drugs

Antilipidaemic Agents

Beyond hypertension, another cardiovascular risk factor that may require aggressive treatment is deranged lipid profile. In addition to lifestyle modification and diet, hypercholesterolaemia or hypertriglyceridaemia may require pharmacological agent to ensure control. The order or priorities in the treatment of hyperlipidaemia is to 1. Lower the LDL cholesterol

2. raise the HDL cholesterol 3. decrease the triglycerides

Most clinical studies on dyslipidaemia have proven the benefit of HMGCoA reductase Inhibitors (fluvastatin, lovastatin, atovastatin, simvastatin) in patients with DM, even with modest elevation in LDL14.

Fibric acid derivatives have some efficacy and well tolerated but nicotinic acid may worsen glycaemic control and increase insulin resistance, thus, niacin is relatively contraindicated in diabetic patients on oral glucose-lowering agents 14.

Antiplatelet Agents

Antiplatelet therapy reduces cardiovascular events in individuals with DM who have coronary artery disease 14. The recommendation is for use of aspirin as secondary prevention of additional coronary events. Although data demonstrating the efficacy in primary prevention of coronary events are lacking, current thinking is to consider aspirin especially in diabetic patients with other coronary risk factors such as hypertension, smoking, hyperlipidaemia. Aspirin therapy is not detrimental to renal function or hypertension and the dose (75 to 325 mg) is the same as in non-diabetics.