Similarities in mortality patterns from influenza in the first half of the 20th century and the rise and fall of ischemic heart disease in the United States: a new hypothesis concerning the coronary heart disease epidemic

Abstract

The classic risk factors for developing coronary heart disease (CHD) explain less than 50% of the decrease in mortality observed since 1950. The transition currently under way, from the degenerative to the infectious-inflammatory paradigm, requires a new causal interpretation of temporal trends. The following is an ecological study based on data from the United States showing that in men and women an association between the age distribution of mortality due to influenza and pneumonia (I&P) associated with the influenza pandemic in 1918-1919 in the 10-49-year age bracket and the distribution of CHD mortality from 1920 to 1985 in survivors from the corresponding birth cohorts. It further shows a significant negative correlation (r = -0.68, p = 0.042) between excess mortality from I&P accumulated in epidemics from 1931 to 1940 (used as indicator for persistent circulation of H1N1 virus combined with vulnerability to infection) and the order of the beginning in the decline in CHD mortality in nine geographic divisions in the United States. In light of current biological knowledge, the data suggest that the 1918 influenza pandemic and the subsequent epidemics up to 1957 might have played a determinant role in the epidemic of CHD mortality registered in the 20th century.

Vitamin E Conditionally Inhibits Atherosclerosis in ApoE Knockout Mice by Anti‐oxidation and Regulation of Vasculature Gene Expressions

“…The etiology of atherosclerosis in humans is still not fully understood and there are thought to be many possible contributory risk factors such as hypercholesterolemia and aging changes [41][42][43][44]. We found in the present study that the ApoE KO mouse spontaneously develops atherosclerosis in an age-dependent manner; however the serum TC and TAG keeps relatively stable at a higher level through the experiment compared to the normal C57BL/6 J mouse.…”

Influenza vaccination: an emerging opportunity to prevent cardiovascular disease

“…Glezen et al [14] demonstrated a similarity in the pattern of cardiovascular disease (CVD) death with that of death attributed to influenza and pneumonia. Azambuja and Duncan [15], in an ecological study of surviving birth cohorts, demonstrated an association between the age distribution of pneumonia -influenza death during the 1918 influenza pandemic and the distribution of CHD mortality from 1920 to 1985, suggesting that the 1918 influenza pandemic may have contributed to the surge in CVD death in the 1950-1960s.…”

Connections: can the 20th century coronary heart disease epidemic reveal something about the 1918 influenza lethality?

“…Based on this rationale, it would make sense to investigate the mechanism resulting in the 1918 influenza lethality by looking at another collective phenomenon proposed to be associated with the vulnerability of the 1918 population to the influenza virus, i.e., the 20th century coronary heart disease (CHD) epidemic (8,(13)(14)(15).…”

“…According to this hypothesis, hypercholesterolemia -the hallmark of CHD cases in the 1950s and 60s -may have been an effect secondary to the influenza priming of 1918 vulnerable individuals for late development of CHD. CHD deaths, however, were probably associated with bursts of auto-immune endothelial inflammation and thrombosis associated with influenza re-infections (8,14,15).…”

“…This sequence of events has been fully demonstrated in cases of Heymann nephritis, an autoimmune disease in which the main auto-antibodies target (megalin/gp330) is also a member of the LDLR family (19). Thus, it would be possible that, in vulnerable individuals, cross-reactive auto-antibodies (and T cells) diverted to the apoB-LDLR interface, first elicited by the 1918 influenza infection and recalled upon influenza reinfections of 1918 primed individuals, resulted in elevated serum cholesterol levels (aggravated by high-fat diets) and lipid deposits co-localized at sites of viral penetration: the left side of the heart, coronary arteries and the aortic arch (8,14,15).…”