The inflammation paradigm: Towards a consensus to explain coronary heart disease mortality in the 20th century

The inflammation paradigm: Towards a consensus to explain coronary heart disease mortality in the 20th century
Maria Ines Azambuja a,*, Aloyzio Achutti b, Richard Levins c
a Department of Social Medicine, School of Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, 4/420, 90035-003 Porto Alegre, RS, Brazil
b Moinhos de Vento Hospital, Porto Alegre, Brazil
c Department of Population and International Health, Harvard School of Public Health, United States
Received 2 November 2007; accepted 8 February 2008
Available online 20 March 2008
KEYWORDS
Coronary disease; Inflammation; Influenza; Arachidonic acid; Lipid hypothesis; Vulnerability
Summary The etiology of coronary heart disease (CHD) has been debated over the last 60 years. There exists an alternative explanation to the rise in CHD mortality, consonant with knowledge about the role of inflammation. It is proposed that a cohort association existed between rates of vulnerability to influenza deaths in 1918 and CHD mortality among survivors from those vulnerable birth cohorts.
According to this hypothesis, hypercholesterolemia may have been a marker of the 1918 immune-priming, with CHD deaths resulting from bursts of endothelial inflammation and thrombosis associated with influenza re-infections during the following decades. We propose a reconsideration of the way we model atherogenesis, from ‘‘initiation’’ and ‘‘promotion’’ to ‘‘vulnerable substrate(s)’’ and ‘‘trigger(s)’’.
Also suggested, based on this hypothesis, is a possible shared condition between vulnerable substrates, which upon triggering, is associated with evolution to acute events, through an imbalance between COX and LOX products. This paradigm has implications for global prevention policies.
 2008 World Heart Federation. Published by Elsevier Ltd. All rights reserved.