Treatment of hypertension

Management of hypertension as part of an aggressive overall treatment strategy to reduce cardiovascular risk in patients with diabetes is clearly important (see also

Chapter 6). Data are also available on the impact of hypertension specifically in patients with diabetes associated with PAD. The Framingham epidemiological study provides observational evidence that patients with high blood pressure are at greater risk of developing intermittent claudication (Murabito etal., 1997). Isolated systolic hypertension, in particular, is very common in the elderly and is closely associated pathophysiologically with increased arterial stiffness, pressure-wave reflection and an increased systolic blood pressure load on the heart causing left ventricular hypertrophy. The UKPDS showed that a 10 mmHg increase in systolic blood pressure was associated with a 25% increase in risk whereas a 10 mmHg lowering in systolic blood pressure translated into a non-significant 16% reduction in risk of lower limb amputation or peripheral vascular disease-related mortality (Figure 8.1) (Adler etal., 2000). The Edinburgh Artery Study even suggested that patients with diabetes no longer had a significantly higher risk of PAD after adjustment for systolic blood pressure and lipid levels (MacGregor etal., 1999).

The Appropriate Blood Pressure Control in Diabetes (ABCD) study showed that in a small subgroup of patients with type 2 diabetes and established PAD and a baseline diastolic blood pressure of 80-89 mmHg (n = 53), intensive antihypertensive treatment with either enalapril or nisoldipine produced a significant reduction in the number of major cardiovascular events from 12 to 3 (P = 0.046). Further analysis of this subgroup suggested that intensive blood pressure control (mean blood pressure over 4 years 128/75 mmHg) effectively cancelled out the excess risk of a cardiovascular event associated with PAD (Mehler etal., 2003).

Beta-blockers have traditionally been considered a relative contraindication in patients with intermittent claudication. However, many controlled studies have found that beta-blockers do not adversely affect walking capacity or symptoms of intermittent claudication (Radack and Deck, 1991). It is therefore thought that beta-blockers can be used safely in this group of patients particularly if strong indication exists, such as previous myocardial infarction, heart failure or resistant hypertension. Similarly, when considering treatments that block the renin-angiotensin system, the risk of underlying renovascular disease should always be considered in patients with PAD, treatment-resistant hypertension and mild renal impairment, especially smokers.

Evidence from more recent trials has advocated lower thresholds for blood pressure treatment as well as lower blood pressure targets among 'high risk' patients with diabetes (Williams etal., 2004) (see also Chapter 6). This includes patients with existing cardiovascular disease and diabetic renal disease. However, the success rates in achieving current targets for blood pressure control among treated hypertensive patients with diabetes are relatively low even in specialist centres (Andrade etal., 2004). This partly reflects the difficulty in lowering systolic blood pressure, especially in the elderly, and it also reflects issues of tolerability and compliance with multiple antihypertensive therapies that are increasingly necessary in patients with diabetes. Many patients develop postural symptoms or other drug-related side effects that limit the capacity to up-titrate medication in pursuit of target blood pressure levels. Nevertheless, even modest blood pressure reductions confer large clinical benefits and clinicians should strive for lower levels of treated blood pressure within the context of what is acceptable and tolerable therapy for individual patients.

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