Risk factors for cerebral hemorrhage in hypertensive patients

Summarized by Robert W. Griffith, MD
January 6, 1999 (Reviewed: January 21, 2005)

It is well recognized that hypertension is the most important risk factor for intracerebral hemorrhage (ICH). It is thought that raised blood pressure causes degenerative changes in the walls of the small arteries, rendering them more likely to rupture. The Melbourne Risk Factor Study Group, amongst other activities, examined the influence of risk factors in different subgroups of hypertensive patients who suffered an ICH.

A collective of 331 consecutive patients with ICH, identified by hospital discharge records and coroner's reports, were analyzed over a three-year period. First-episode primary ICH had to be diagnosed by computerized tomography (CT), autopsy or magnetic resonance imaging. Age limits were 18 to 80 years, and nursing home patients were excluded.

Case-control subjects were identified among the patient's near neighbors - they were matched for sex, age (+ 5 years), and work activities. The same nurse who interviewed the stroke patient (or the closest available informant, if the patient was dead or incapacitated) interviewed the matched control. A validated structured questionnaire was used, encompassing information on smoking, alcohol consumption, physical activity and medical history. Details of medication were also obtained, validated by prescription records in over 70% of subjects.

Adjusted odds ratio (OR) of ICH was calculated for different categories of hypertensive patients - the reference category was made up of individuals who reported never having hypertension or having been treated with antihypertensive agents.

Analysis of the results showed that hypertension (defined as a history of the condition reported to the patient by a medical practitioner) carried an OR of 2.45 (95% CI, 1.61 to 3.73). The impact of hypertension was greatest among those younger than 55, and decreased in the older age categories.

An important finding was that the risk of ICH varied according to patients_ current or past use of antihypertensive drugs. The OR was 1.95 (95% CI, 1.20 to 3.16) for those taking medication for high blood pressure, but rose significantly to 4.98 (95% CI, 2.25 to 11.02) in those patients who had taken antihypertensive drugs in the past, but had discontinued them (p=0.002). The majority of those discontinuing their medication (90%) had done so for more than one month.

Hypertensive current smokers, compared to normotensive current smokers, had an OR of 6.12. The same comparison for never-smokers gave an OR of 2.92, similar to the overall OR for hypertension. Previous smokers with hypertension had an OR of 1.30.

The OR for hypertensive patients was not increased to a significant degree for gender, cardiovascular disease, diabetes, exercise, alcohol use, or serum cholesterol level categories. Hypertension had no influence on the site or size - based on CT - of fatal or non-fatal ICH. However, hypertension was a greater risk factor for fatal (OR 10.84) than for non-fatal (OR 1.98) hemorrhage, to a significant degree (p=0.026).

The findings show that the risk of ICH is more than doubled in patients ever diagnosed as having hypertension, compared to normotensives. Among those treated with antihypertensive drugs, the risk is significantly higher (doubled again) in those who have discontinued treatment, compared with those who continue on their medication. The authors suggest that the thinning of the arterial wall that occurs with the use of antihypertensives render the vessel more liable to rupture with the return of higher pressure on stopping treatment. Unfortunately the study did not determine the reasons given for cessation of medication; also, actual blood pressure readings were not available in the data for analysis.

Recently there have been reports of successful treatment of hypertension by salt restriction and weight loss, to the extent that medication can be discontinued.¹ It should be obvious that antihypertensive drug treatment should not be discontinued while raised blood pressure exists. Moreover, those patients who can control their hypertension adequately without medication need to have their blood pressure constantly monitored.

The decline in the relative risk of ICH with increasing age in hypertensive subjects may be due to thickening of arterial vessels age, and/or the fact that hypertension is recognized and treated to a greater degree in the elderly. Current smokers, as opposed to previous smokers and never-smokers, have a clearly increased risk; this may be related to a weakening of vessels caused by nicotine action on the endothelium and media of small vessels.

This study provides the first direct evidence of a link between stopping antihypertensive medication and the risk of a cerebral hemorrhage. How should you advise your patients? In the words of the principal author, Dr Thrift, ". . . if you have high blood pressure, keep taking those medications, have regular blood pressure checks, and give up smoking".

The full text of this article can be viewed at:
http://hyper.ahajournals.org/cgi/content/full/31/6/1223

Source

• Three important subgroups of hypertensive persons at greater risk of intracerebral hemorrhage AG. Thrift, JJ. McNeil, A. Forbes, Hypertension, 1998, vol. 31, pp. 1223--1229

Footnotes
1. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). PK. Whelton, LJ. Appel, MA. Espeland,  et al., JAMA, 1998, vol. 279, pp. 839--846

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