The risk of heart attack and ischemic stroke in patients aged 50 and older more than doubled in the 2 weeks after even mild influenza in those with few risk factors and more than quadrupled in high-risk patients with severe cases, with elevated risk persisting for 2 months, according to a self-controlled case series in The Journal of Infectious Diseases.
Researchers in Valencia, Spain, assessed the link between flu infection diagnosed in the primary care or hospital settings and 90-day risk of heart attack and ischemic stroke in nearly 2.2 million older patients from January 2011 to December 2018.
The study authors noted growing evidence that respiratory infections—particularly flu—can trigger or exacerbate cardiovascular diseases, the world's leading cause of death.
Risk depended on time after infection
Seven percent of participants had a flu diagnosis or test during the study period. A total of 5.5% of participants had at least one clinical flu diagnosis, and 1.7% were tested for flu at a hospital, with 30% positive results. Of the clinically diagnosed flu patients, 84 had a heart attack or ischemic stroke within 90 days and 1,618 did so during baseline (periods of no flu exposure).
Stratification by risk subperiod revealed incidence rate ratios (IRRs) of cardiovascular events of 2.21 and 2.62 in the first 7 days and 8 to 14 days of infection, respectively. No significant increase was seen during days 15 to 29, 30 to 60, or 61 to 90 days after infection.
Among patients with lab-confirmed flu, 48 cardiovascular events occurred in the next 90 days, and 558 occurred during baseline. The IRRs for cardiovascular events were 4.40, 5.09, 2.47, and 2.24 during 1 to 7, 8 to 14, 15 to 29, and 30 to 60 days, respectively. No significant increase was observed 61 to 90 days after infection.
In patients with negative results, 153 cardiovascular events occurred in the 90 days after the flu test, and 1,467 occurred during baseline. The IRRs for cardiovascular events were 5.16, 4.19, 2.45, 2.55, and 1.68 during days 1 to 7, 8 to 14, 15 to 29, 30 to 60, and 61 to 90, respectively.
Flu virus may have role in plaque displacement
An analysis of the 65-and-older age-group revealed increased IRRs for cardiovascular events (in comparison with the entire 50-and-older group) in the 7 days after a clinical flu diagnosis and the 60 days after a lab-confirmed infection.
In comparison with the overall and clinical diagnosed groups, patients with lab-confirmed or negative results were older (62 and 64 years vs 70 years, respectively) and had higher death rates (14% and 18% vs 43% and 52% respectively), a greater proportion of patients with at least four underlying medical conditions (11% and 31% vs 54% and 53%), and a higher percentage of patients with two or more cardiovascular events.
This work reinforces the official recommendations for influenza prevention in at-risk groups and should also increase the awareness of even milder influenza infection and its possible complications in the general population.
The study results provide further evidence that while several pathogens are thought to increase cardiovascular risk through systemic infection and inflammation, the flu virus may have a more specific role in direct cardiac infection and endothelial dysfunction, leading to destabilization and rupture of existing atherosclerotic plaques, the authors said.
"The transient increase of the association, its gradient after influenza infection and the demonstration by 4 different sensitivity analyses provide further evidence supporting causality," the researchers wrote. "This work reinforces the official recommendations for influenza prevention in at-risk groups and should also increase the awareness of even milder influenza infection and its possible complications in the general population."
