title: Spanish flu and early 20th-century expansion of a coronary heart disease-prone subpopulation.
abstract: According to Stephen Jay Gould, "we have a strong preference for seeing trends as entities moving somewhere." However, trends may instead be the product of relative expansions and contractions of different subpopulations constituting the system. Variation in attributes of coronary heart disease cases during the decline in coronary heart disease mortality suggests a change in the primary source-subpopulation of cases over time. It is proposed that an early 20th-century expansion of a coronary heart disease-prone subpopulation, characterized by high serum-cholesterol phenotype and high case-fatality--which contributed to most of the coronary heart disease cases and deaths during the 1960s--may have been a late result of the 1918 influenza pandemic. The same unusual immune response to infection that in 1918 killed preferentially men, whites, and those born from 1880 to 1900 (20-40 years old) may have "primed" survivors of those birth cohorts to late coronary heart disease mortality. Ecologic evidence in favor of a birth cohort and geographic association between both epidemics is presented. Cross-reactive auto-immune response upon reinfection could explain the excess coronary heart disease deaths reported during influenza epidemics from the late 1920s onward. Mimicry between the viral hemagglutinin and the apolipoprotein B or the low-density lipoprotein receptor could be the link between infection and hypercholesterolemia. The extinction of those birth cohorts would result in a relative increase in cases coming from a 2nd subpopulation, which was characterized by insulin resistance and chronic expression of low-grade inflammation markers and was comparatively less vulnerable to die acutely from coronary heart disease.
authors.affiliation: Department of Social Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil. miazambuja@terra.com.br
authors.forename: Maria Inês Reinert
authors.initials: MI
authors.lastname: Azambuja
mesh_terms: D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology / Q000266:history / Q000401:mortality*; D004196:Disease Outbreaks / Q000266:history*; D016021:Epidemiologic Studies; D005260:Female; D049673:History, 20th Century; D006801:Humans; D007251:Influenza, Human / Q000150:complications / Q000266:history / Q000401:mortality*; D008297:Male; D011159:Population Surveillance; D012307:Risk Factors; D014481:United States / Q000453:epidemiology