Hypertension is the single most important and potentially reversible risk factor for cerebrovascular disease in both diabetic and non-diabetic individuals (see also Chapter 6). Epidemiological studies confirm that usual systolic and diastolic blood pressure levels are directly and continuously associated with risk of stroke (both cerebral infarction and primary intracerebral haemorrhage) in patients with and without a previous history of hypertension (Prospective Studies Collaboration, 1995; Eastern Stroke and Coronary Heart Disease Collaborative Research Group, 1998). In addition, a similar linear relationship exists between systolic and diastolic blood pressure and risk of recurrent cerebrovascular events in survivors of stroke and TIA (Rodgers etal., 1996). Reducing diastolic blood pressure by 5-6mmHg in people with hypertension and no history of cerebrovascular disease reduces their risk of stroke by approximately one-third, with all major classes of antihypertensive agents appearing equally effective (Blood Pressure Lowering Treatment Trialists' Collaboration, 2000). Furthermore, drug interventions to lower blood pressure have been shown to reduce the risk of stroke recurrence in hypertensive stroke survivors (INDANA Project Collaborators, 1997). Whilst it is accepted that hypertension is a major determinant of stroke risk in diabetics, the majority of patients have multiple risk factors such as dyslipidaemia, ischaemic heart disease and peripheral vascular disease that may influence the choice of antihypertensive therapy. Trial evidence suggests that tight diabetic control may not directly reduce the risk of stroke and TIA (UK Prospective Diabetes Study (UKPDS) Group, 1998) and clinicians therefore also need to direct attention towards the management of other modifiable vascular risk factors such as hypertension.
The United Kingdom Prospective Diabetes Study incorporated a randomised controlled trial (also called the 'Hypertension in Diabetes Study', or HDS) to establish if tight control of blood pressure (< 150/85mmHg) reduced morbidity and mortality in patients with type 2 diabetes (UK Prospective Diabetes Study Group, 1998). Treated hypertensive diabetics whose blood pressure was above this target level and those who were previously untreated (>160/ > 90 mmHg) were randomised to receive either intensive or less intensive blood pressure lowering therapy. The intensive treatment comprised an angiotensin-converting enzyme (ACE) inhibitor (captopril) or a beta-blocker (atenolol), with a target blood pressure of < 150/85. The other treatment limb aimed for less tight control of blood pressure (< 180/105), avoiding ACE inhibitors and beta-blockers. Almost one-third (29%) of patients randomised to the tight control group needed three or more agents to control their blood pressure, compared with 11% in the less intensive treatment group. Tight control resulted in significantly lower blood pressure; the mean blood pressure over 9 years of follow-up was 144/82 in the intensive treatment group compared with 154/87 in the other limb. After a median follow-up period of 8.4 years, intensive management of hypertension in these UKPDS patients resulted in a 24% relative risk reduction for the development of any endpoint related to diabetes. There was no significant difference in diabetic control between the intensive and less-intensive treatment groups (mean HbA1c 7.2% for both). Intensive treatment led to a highly significant 44% relative reduction in fatal or non-fatal stroke, but no significant decrease in rates of myocardial infarction.
These results are comparable with those seen in other trials of blood-pressure-lowering treatment in older people (Dahlof etal., 1991; SHEP Co-operative Research Group, 1991). Thus, intensive glycaemic control in patients with type 2 diabetes is not sufficient to reduce their risk of stroke; simultaneous management of hypertension is also necessary. The UK Prospective Diabetes Study Group (1998) also showed that intensive blood pressure treatment would probably require combination therapy, including beta-blockers or ACE inhibitors. It should be noted that even in the their tight control group, the mean level of blood pressure achieved was still higher than the current UK recommended target of < 130/80mmHg for clinic readings (Williams etal., 2004). However, this trial did demonstrate that the lowest risk of complications due to diabetes was seen in patients with systolic blood pressure < 120 mmHg, in line with current recommendations (Adler etal., 2000).
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