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Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study

Zanchetti, Albertoa; Hansson, Lennartb; Dahlöf, Björnc; Elmfeldt, Dagd; Kjeldsen, Sverree; Kolloch, Rainerf; Larochelle, Pierreg; McInnes, Gordon T.h; Mallion, Jean-Micheli; Ruilope, Luisj; Wedel, Hans*; on behalf of the HOT Study Group

Original papers: Therapeutic trials

Background: The Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18 790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk, and it has been found that, despite intensive blood pressure lowering in all risk strata, morbid event rates increased with increasing risk stratum.

Objectives: Previously analysed global risk strata were based on combinations of risk factors. The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk, despite good BP control.

Methods: Risk ratios (RR) for patients with and those without a risk factor were calculated with 95% confidence intervals (CI) using a Cox proportional hazard model, and adjusted for all variables except the one under examination.

Results: For all risk factors considered and for all types of event, RR were always greater than 1, indicating a greater risk in the presence, compared with that in the absence of each factor. The male gender was a statistically significant risk for cardiovascular (CV) events, CV and total mortality and particularly for myocardial infarction (MI); age 65 years for CV events, stroke, CV and particularly total mortality; smoking for all events analysed, but particularly for total mortality (twice higher in smokers than in non-smokers); high serum cholesterol (> 6.8 mmol/l) for CV events, MI and CV mortality; high serum creatinine (> 155 μmol/l) for CV events, stroke, CV and total mortality; diabetes for CV events, stroke, total mortality and particularly CV mortality; and ischaemic heart disease for all events analysed. Adjusted RR were often close to or greater than 2.

Conclusions: Each of the risk factors considered was found to be an important cause of residual risk, despite good BP control. These findings emphasize the importance of addressing other correctable risk factors, e.g. smoking, hypercholesterolaemia and diabetes, as well as rigorous control of blood pressure, and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest.

aCentro di Fisiologia Clinica e Ipertensione, Università di Milano, Ospedale Maggiore and Istituto Auxologico Italiano, Milano, Italy, bDepartment of Public Health and Caring Sciences, Hypertension Research, Uppsala University, Uppsala, Sweden, cClinical Trial Unit, University of Göteborg, Östra Hospital, Göteborg, Sweden, dAstraZeneca R&D, Molndal, and Department of Public Health and Caring Sciences, Primary Medicine, Uppsala University , Uppsala, Sweden, eDepartment of Cardiology, Ullevaal University Hospital Oslo, Norway, fMedizinische Klinik, Krankenanstalten Gilead, University of Münster Bielefeld, Germany, gCentre de Recherche, Hôtel Dieu, Montréal, Québec, Canada, hUniversity of Glasgow, Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK, iMédecine Interne et Cardiologie, Hôpital A. Michallon, Université de Grenoble, France, jHypertension Unit, Hospital 12 de Octubre, Madrid, Spain and kNordic School of Public Health, Göteborg, Sweden; *see Appendix.

Received 3 January 2001

Revised 28 February 2001

Accepted 6 March 2001

Correspondence and requests for reprints to Professor Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione, Università di Milano – Ospedale Maggiore, Via F. Sforza, 35, 20122 Milan, Italy. Tel +39-02-55011295; fax: +39-02-55187506; e-mail:

© 2001 Lippincott Williams & Wilkins, Inc.