Factors that increase the risk of cancer during adult life may also increase the risk of cancer when they act in utero (eg, ionising radiation and diethylstilboestrol in human beings and chemicals in animals). The existing empirical data seem to be compatible with the hypothesis that increased concentrations of oestrogens in pregnancy increase the probability of future occurrence of breast cancer in daughters.

There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.

Two platelet mechanisms contribute to haemostasis and thrombosis. (1) Compounds such as thrombin activate glycoprotein IIb/IIIa; fibrinogen is the ligand. The cyclooxygenase pathway is involved and so this process is aspirin sensitive. (2) Shearing forces alone activate a different domain on glycoprotein IIb/IIIa; von Willebrand's factor is the ligand. This process is probably non-enzymatic and is aspirin insensitive. The prevention of shear-induced platelet activation may prove to be more rewarding therapeutically than inhibition of aspirin sensitive pathways.