The Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) was one of the earliest trials in the UK and Europe to show the benefits of cholesterol lowering with statins. ASCOT also demonstrated that newer drug combinations were superior to earlier treatments when lowering blood pressure. Analyses of the ASCOT database have led to several important publications with implications for clinical management and future research. This database is held at ICCH.
Dr Ajay Gupta has looked at which factors predicted the likelihood of developing diabetes in hypertensive patients. This research showed that patients treated with the combination of two newer blood pressure lowering drugs (the calcium channel blocking drug, amlodipine and perindopril, an angiotensin-converting enzyme inhibitor) resulted in about one-third lower risk of developing diabetes compared with those treated with older drug combinations (betablocker and diuretic). In addition, baseline fasting plasma glucose, body mass index, serum triglycerides (fats within the blood) and systolic blood pressure were associated with increased risk for diabetes.
Conversely, high baseline levels of high-density lipoprotein cholesterol (‘good cholesterol’), alcohol intake and age >55 years were protective. Increased levels of fasting plasma glucose and the development of diabetes increased the risk of cardiovascular outcomes. On this basis, Dr Gupta suggests that the adverse effects of the beta-blocker plus diuretic combination used in ASCOT (atenolol plus thiazide) may be responsible.
In a second project, Dr Gupta and Dr Stylianos Mastorantonakis, used the ASCOT database to show that the metabolic syndrome (a clustering of risk factors for cardiovascular disease, including hypertension, dyslipidemia and impaired glucose metabolism), was associated with increased risk of diabetes, stroke and death, beyond that associated with its individual components. Since, in ASCOT, cancer was a major cause of death (after cardiovascular causes), they plan to investigate whether the metabolic syndrome is also an independent predictor for cancer morbidity and mortality, and if so, whether insulin resistance represents a possible link.