From April 4 through May 2, 1947, 6.35 million New Yorkers were vaccinated with the NYC Board of Health vaccinia strain (5
). We used newspaper accounts and NYC Department of Health records to estimate the number of adults vaccinated on each of the 29 days (5
). Since all of the 2003 cardiac events occurred from 4 to 17 days after vaccination, the 1947 vaccination numbers were divided equally across the same 14-day period to calculate the person-time at risk for potential cardiac death. On the basis of these estimates, we identified the 2- and 4-week “peak” risk periods in 1947.
We obtained all death certificates issued in NYC for the 4-month period between March and June, 1946–1948, from the NYC Municipal Archive. Cause of death was coded according to the International Classification of Diseases, 5th Revision (ICD-5) (6
). We abstracted the date of death, age of decedent, and ICD-5–coded primary and other cause of death into an electronic database. We defined cause of death as “cardiac” if the ICD-5 codes for either cause included pericarditis (090), acute endocarditis (091), chronic endocarditis (092), myocardial disease (093), coronary artery diseases (094), and other disease of the heart (095).
We compared daily death rates during the postvaccination risk periods with rates at other times during the study period. We used Poisson regression, a generalized linear model appropriate for analysis of discrete data, to model counts of cardiac deaths (7
). Counts were used instead of rates, as NYC’s population remained relatively constant during the study’s 3-year timeframe. We also adjusted for temporal trends in the data: a long-term trend from 1946 to 1948 (defined by weeks since January 1, 1946) and a seasonal trend between March and June (defined by days since March 1 for any given year). Secular trends were modeled with linear and quadratic terms. The main model included all cardiac deaths as the outcome variable and a dichotomous “exposure” variable indicating whether the death occurred during the 2-week risk period. Additional models examined subsets of cardiac disease and all-cause death as outcomes, as well as adjusting for noncardiac death volume.
An a priori power analysis found that the model had >90% power to detect a 5% increase in cardiac fatalities in the at-risk period. While this power would be more than sufficient to detect an excess of 2 deaths in 29,584 civilians (approximately 400 deaths in the 1947 NYC population of 6,000,000), it would not be able to detect very small elevations in risk.
At the height of the 1947 vaccination campaign, from April 17 to April 21, 500,000 to 1 million people were vaccinated daily (). The 2-week at-risk period in 1947 was estimated to be April 22 to May 5, which encompassed 84% of the projected at-risk person-time for adverse cardiac complications. The 4-week period was identified as April 16 to May 13 and included 99% of the at-risk person-time.
Adult vaccination doses administered and estimated person-time at risk for fatal cardiac adverse effects, New York City, 1947.
During the months under review in 1946–1948, 81,529 death certificates were recorded, including 519 (0.6%) records with an illegible cause of death. Of the remaining 81,010 records, 48% had heart disease listed as a cause of death. A total of 9,112 (11%) specifically referred to coronary artery or atherosclerotic disease. The number of daily deaths from heart disease in the months of March to June of 1946, 1947, and 1948 ranged from 72 to 149, with an increasing long-term trend and decreasing seasonal trend (). In the 2-week estimated risk period in 1947, 1,545 cardiac deaths occurred of 3,156 total deaths (average 110 deaths per day, range 91–119 deaths) ().
Daily deaths from cardiac causes, New York City, March to June, 1946–1948.
Death counts by cause of death and postvaccination exposure period
In the main regression model (), no independent association was found between cardiac deaths and the 2-week estimated risk period. The findings remained nonsignificant when the model was restricted to those 50 to 64 years of age and when adjustments for noncardiac deaths were made (rate ratio 1.01; 95% confidence interval 0.95 to 1.06). Additional analyses examining different outcomes (all deaths, atherosclerotic deaths, or deaths due to myopericarditis) did not show any significant increase in deaths, nor did expanding the estimated risk period to 4 weeks.
Rate ratio (RR) and 95% confidence interval (CI) of cardiac death rates comparing postvaccination to reference periods,a New York City, March–June, 1946–1948