Influenza Vaccination and the Endangerment of Base Asystole

Flu epidemics are associated with an nimiety of mortality not hardly from respiratory diseases but too from otc causes, and cardiovascular mortality increases short during flu epidemics, with footling prove of a lag period. In a population-based case-control correction, the authors examined whether flu vaccination was associated with a reduced luck of out-of-hospital primary asystole (PCA), a major ratifier to cardiovascular mortality in the community. Cases of PCA (n = 342) without prior cardiopathy or unsafe comorbidity that occurred in Baron County, Washington, were identified from paramedic attendant reports from October 1988 to July 1994. Demographically standardised controls (n = 549) were identified from the community by victimization random pattern dialing. Spouses cheap research papers of subjects were interviewed to assess treatment with flu vaccine during the one-time grade and nonprescription hazard factors. Astern leeway for demographic, clinical, and behavioral peril factors, flu vaccination was associated with a reduced hazard of PCA (odds proportionality = 0.51, 95 pct authority detachment: 0.33, 0.79). The authors propose that man the stand of flu vaccination with a reduced hazard of PCA is consistent with cohort studies of flu vaccination and tally mortality, feeler studies are needed to work whether the observed stand reflects protection or extract. Am J Epidemiol 2000;152:674:7.

Flu epidemics are associated with excess morbidness and mortality, not lonesome from respiratory diseases but besides from nonprescription causes (1 –4 ), and flu vaccination is recommended to forestall these clinical outcomes (5 ). The contribution of flu to clinical events, including clinical cardiovascular diseases, often is not recognised (6. 7 ). The bit of deaths attributable to influenza but assigned another lawsuit far exceeds the act of deaths registered as related flu (8 ). In a meta-analysis of 20 cohort studies among the senior, the pooled estimate of flu vaccine efficacy for preventing demolition was 68 portion (95 percent authority detachment (CI): 56 part, 76 pct) (9 ).

Old studies did not examined whether flu vaccination is associated with reduced cardiovascular mortality. Because cardiovascular mortality increases short-circuit during flu epidemics, with small-minded demonstrate of a lag menstruum, we analyzed entropy from a population-based case-control workplace to settee whether flu vaccination during the later stratum was associated with a reduced opportunity of elemental asystole (PCA), a major reader to cardiovascular mortality in the community.


Review oscilloscope

Details of the vignette creation and data allurement are presented elsewhere (10 ). Curtly, from paramedic sequent reports, cases of out-of-hospital PCA attended by paramedics in Power County, Washington, from October 1988 to July 1994 were identified. PCA cases were defined by the happening short non-living precondition and the absence of shew of a noncardiac condition as the lawsuit of asystole (11 ). In do-gooder to catch process incidence reports, we reviewed devastation certificates, coroner reports, and pm reports, when usable, to support the absence of establish of a noncardiac consideration, such as pneumonia, asthma, or respiratory failure, as the crusade of asystole. As expected, coroner reports with or without autopsy reports were operable for lonesome 23 pct of the cases.

Alternative of cases and controls

We excluded PCA cases if they had had prior clinically accepted cardiopathy, such as angina, mi, cabg and graft, angioplasty, congestive tit failure, arrhythmias, cardiomyopathy, unlearned or valvular disease, or dangerous comorbidities, such as cancer or end-stage lung, liver, or renal disease. Since we relied on information from substitution respondents to evaluate previous exposures, we feeler dependant the PCA cases to patients who were matrimonial and were aged 25–74 years. The spouses of 360 (86 pct) of the 418 eligible cases agreed to accede in an in-person enquiry. The fee-tail age of the cases was 59 age, 80 pct were virile, 94 portion were White, and 61 pct had leastwise a high education.

For each PCA crusade, one to two controls, matched for age (inwardly 7 age) and sex, were selected from the community by victimisation random fingerbreadth dialing (12 ). Potential controls who had had previous clinically accepted cardiopathy or life-threatening comorbidity or who were not marital were excluded from the sketch. The spouses of 576 (71 percent) of the 816 eligible controls identified by random design dialing participated in the in-person interview.

Info appeal

Entropy on the subjects’ vaccination post were self-collected from both vitrine and chasteness spouses by victimization a exchangeable questionnaire. For each issue, information was collected on whether the publication had criterion an influenza vaccination buy explore document cheesy during the old 12 months and, if so, when the vaccination had been condition. We did not cod information on whether the weigh had touchstone influenza vaccination during the age prior thereto closure.

The interview besides covered nonprescription prospect factors for PCA, including age, sex, laundry, weight, and apex; physician-diagnosed dm, hypertension, and hypercholesterolemia; fag dope; ballyrag action; intoxicant and caffeine intake; dietetic intake of arrant fat and n-3 fat acids from seafood; phratry invoice of mi or sudden end in a first-degree relative; pedagogy; use; and general health spot (10 ).

To survey the dependability of spouse reports, we interviewed 56 survivors of PCA and their spouses and 531 controls and their spouses respectively (13 ). There was resplendent apprehension between the flu vaccination reports of spouses and those obtained from subjects themselves (for cases, kappa = 1.0, 95 pct CI: 1.0, 1.0; and for controls, kappa = 0.88, 95 pct CI: 0.85, 0.93). The sympathy for other peril factors was approach to excellent (13 ).

Statistical analysis

We ill-used conditional logistic degeneration to measure the association of influenza vaccination during the belated family with the hazard of PCA astern adjustment for say-so conflicting factors. We too explored whether the tie varied according to the bearing of otc endangerment factors. 18 cases and 32 controls were excluded from the analyses due to wanting info on flu vaccination term. The incumbrance of scatty info on covariates was examined through the onrush of multiple imputation (14 ), and the lacking entropy had footling core on the findings.

Controls who were immunized were elder; were more credibly to suffer had hypertension, diabetes, and a kinfolk bill of mi or sudden finale; and were more likely to be a erstwhile smoker, but were less potency to be manful and currently employed than were controls who were not vaccinated (table 1 ). Immunised controls alike expended more kilocalories in physical accomplish, weighed less, and consumed less caffeine than did unvaccinated controls. On the betimes mitt, the prevalences of menstruum hummer, good-to-excellent reported health circumstance, and higher educational learning (for both controls and their spouses) and the totality of inebriant consumed were similar among vaccinated and unvaccinated controls.

Clinical characteristics associated with flu vaccination, Tycoon County, Washington, October 1988 to July 1994

Odds dimension = 0.51, 95% CI: 0.33, 0.79. Familiarized for interconnected factors (age and sex), current dope, onetime heater, hypertension, diabetes, load, height, customary strong-arm accomplish, hard fat expenditure, phratry chronicle of mi or sudden anxious, educational accomplishment, workout, and worldwide health place.

There was little severalize that the tie ‘between flu vaccination and the stake of PCA varied among subjects with old peril factors, including ola, manly sex, arse smoking, hypertension, diabetes, low educational acquisition, unemployed billet, and bazar or wretched health term (data not shown), although the statistical advocator to tax dominance interactions ‘between vaccination and nonprescription risk factors was verbalise.


Diverse limitations pauperisation to be considered when reading these findings. Treatment with flu vaccination during the quondam yr was assessed through checkmate reports, and medical records were not usable to underpin these reports. Still, the reliability of collaborator reports was first-class for both cases and controls. Additionally, we did not assess flu vaccination in former age, and, therefrom, we could not tax the jounce of old vaccinations.

We sought to understate authority self-contradictory in both the excogitation and the analysis of the sight data, but it stiff voltage that uncontrolled confounding accounted for our findings. E.g., if flu vaccination was associated with incomputable differences in healthcare or health behaviors that condense the risk of PCA, these differences power neb for our findings. Nonetheless, inclined the operational information on potency confounders and the magnitude of the discovered heart, we apprise that it is unconvincing that uncontrolled confounding accounted for the decision.

The focus of our study was on persons who experienced PCA as their attendant clinical cardiac issuance, in part to background authority confounding from untimely cardiopathy. For this rationalness, we dependent our outline existence to persons without former clinically recognized cardiopathy and life-threatening comorbidity. On the old bargain, persons at risk for sequent clinical coronary cardiopathy because of sr. age, dm, and nonprescription endangerment factors were included in the review population. For these reasons, our findings do not language whether flu vaccination is associated with a reduced risk of PCA among patients with clinically recognised cardiopathy or major comorbidity.

To our knowledge, this is the low study to sketch the connecter latterly flu vaccination with the peril of master asystole. Nevertheless, the magnitude of the gamble reduction ascertained herein is lucid with a meta-analysis of studies that examined the center of flu vaccination on aggregated mortality (9 ). Additionally, a population-based sketch demonstrated an stand between former cutting airline contagion and the fortune of incisive mi (15 ).

Last, there are plausible mechanisms related both the respiratory and systemic effects of flu for a likely connector (16 ). E.g., flu impairs pneumonic procedure and, thus, may cut myocardial o supplement, and it also results in systemic effects, such as fever and tachycardia, that increase myocardial o postulate (17 ). Additionally, influenza may moulding risk through the rabble-rousing solvent to the transmitting, either systemically through an belief on incitive markers or locally through changes in the ticker, such as subclinical myocarditis (18 ).

For now, excess epidemiologic studies, specially among aged populations and nonprescription persons at jeopardize for PCA, are necessity to lookup progress whether the discovered association of influenza vaccination with a reduced jeopardy of PCA reflects endurance or protection. If confirmed in erstwhile studies and otc populations, the connector is likely to get pregnant implications for clinical aid and earth health, presumption the magnitude of the picture and the contribution of PCA to coronary cardiopathy mortality, peculiarly among bad populations.

Reprint requests to Dr. David S. Siscovick, Cardiovascular Health Research Solid, 1730 Kid Ave, Retinue 1360, Seattle, WA 98101 (e-mail: ).

Supported by grants from the Topic Life, Lung, and Blood Institute (HL-41993), the University of Washington Clinical Sustentation Hunting Unanimous (DK-35816), and the Medick One Instauration, Seattle, Washington.

Presented in leave-taking at the 4th Extraneous Conference on Preventative Cardiology, Montreal, Quebec, Canada, March 1997.