title: Are blood pressure and diabetes additive or synergistic risk factors? Outcome in 8494 subjects randomly recruited from 10 populations.
abstract: It remains unknown whether diabetes and high blood pressure (BP) are simply additive risk factors for cardiovascular outcome or whether they act synergistically and potentiate one another. We performed 24-h ambulatory BP monitoring in 8494 subjects (mean age, 54.6 years; 47.0% women; 6.9% diabetic patients) enrolled in prospective population studies in 10 countries. In multivariable-adjusted Cox regression, we assessed the additive as opposed to the synergistic effects of BP and diabetes in relation to a composite cardiovascular endpoint by testing the significance of appropriate interaction terms. During 10.6 years (median follow-up), 1066 participants had a cardiovascular complication. Diabetes mellitus as well as the 24-h ambulatory BP were independent and powerful predictors of the composite cardiovascular endpoint. However, there was no synergistic interaction between diabetes and 24-h, daytime, or nighttime, systolic or diastolic ambulatory BP (P for interaction, 0.07P0.97). The only exception was a borderline synergistic effect between diabetes and daytime diastolic BP in relation to the composite cardiovascular endpoint (P=0.04). In diabetic patients, with normotension as the reference group, the adjusted hazard ratios for the cardiovascular endpoint were 1.35 (95% confidence interval (CI), 0.87-2.11) for white-coat hypertension, 1.78 (95% CI, 1.22-2.60) for masked hypertension and 2.44 (95% CI, 1.92-3.11) for sustained hypertension. The hazard ratios for non-diabetic subjects were not different from those of diabetic patients (P-values for interaction, 0.09P0.72). In conclusion, in a large international population-based database, both diabetes mellitus and BP contributed equally to the risk of cardiovascular complications without evidence for a synergistic effect.
authors.affiliation: The Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sehestedt
authors.forename: Tine W
authors.initials: TW
authors.lastname: Hansen
authors.forename: Yan
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authors.lastname: Li
authors.forename: Tom
authors.initials: T
authors.lastname: Richart
authors.forename: Jose
authors.initials: J
authors.lastname: Boggia
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stolarz-Skrzypek
authors.forename: Edoardo
authors.initials: E
authors.lastname: Casiglia
authors.forename: Valérie
authors.initials: V
authors.lastname: Tikhonoff
authors.forename: Sofia
authors.initials: S
authors.lastname: Malyutina
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikitin
authors.forename: Kristina
authors.initials: K
authors.lastname: Björklund-Bodegård
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jeppesen
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
authors.forename: Jiguang
authors.initials: J
authors.lastname: Wang
authors.forename: Edgardo
authors.initials: E
authors.lastname: Sandoya
authors.forename: Kalina
authors.initials: K
authors.lastname: Kawecka-Jaszcz
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002318:Cardiovascular Diseases / Q000209:etiology*; D048909:Diabetes Complications / Q000209:etiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001786:Blood Glucose