We found that the 10-year risk for cardiovascular disease was not higher among adults who had severe gastroenteritis and was actually lower among those who had mild gastroenteritis during an E. coli O157:H7 outbreak.
We previously found increased risks of hypertension, chronic kidney disease and self-reported cardiovascular disease among adults who experienced acute gastroenteritis after drinking water contaminated with E. coli
Although we used objective, standardized measures to diagnose hypertension and chronic kidney disease, our previous study relied on participant recall of major cardiovascular events, and there was significant loss to follow-up. This prompted us to conduct a more accurate assessment of cardiovascular risk by linking data from the Walkerton Health Study to Ontario’s health care databases, allowing the use of administrative codes to determine outcomes, which is more reliable than self-report. Only 57% of self-reported cardiovascular events were corroborated by validated database codes for cardiovascular-related hospitalization. No association between acute gastroenteritis and cardiovascular-related events was evident.
These discrepant results suggest 2 possible scenarios: either there is no causal link between E. coli
O157:H7 gastroenteritis and cardiovascular events, or an association exists but we were unable to detect it in the present study. Despite the robust association with hypertension,23,27
it is possible that the biological mechanisms thought to link E. coli
O157:H7 and cardiovascular disease are inadequate to precipitate major cardiovascular events — or perhaps 10 years is not long enough for such events to manifest. Alternatively, by virtue of participating in the Walkerton study, participants received extra health care and screening for hypertension and kidney disease.53
These risk factors for cardiovascular disease are asymptomatic and often go untreated in the absence of active surveillance, so diagnosis and treatment of these conditions may have been greater for Walkerton participants compared with their unexposed counterparts in the surrounding communities.
Among Walkerton participants with hypertension, the proportion receiving treatment increased from 18% to 77% during follow-up, and the overall proportion with elevated systolic/diastolic blood pressure (> 140/90 mm Hg) decreased from 25% to 20%.53
To examine this further, we compared the rates of antihypertensive prescription use before and after the study among those with provincial drug benefits. Overall rates of antihypertensive prescriptions were similar between groups at both time points; however, between 1999 and 2009, an 8-fold rise in prescriptions for ACE inhibitors or ARBs among Walkerton participants occurred (≤ 7% to 34%), compared with a 3-fold rise among residents of surrounding communities (14% to 40%). Although prescription rates were not appreciably different in 2009, it is possible that the greater relative increase in ACE or ARB use among Walkerton participants played a role in preventing cardiovascular disease among study participants.
Strengths and limitations
Our study examined long-term health outcomes after acute bacterial gastroenteritis caused by E. coli
O157:H7 in a well-defined cohort with minimal loss to follow-up (2.3%). All outcomes were measured using validated codes with high specificities and positive predictive values.36–44
The method of determining acute gastrointestinal illness at the time of the outbreak was validated using both public health and medical records.28
Although we could not reliably determine the cause of death from our data sources, cardiovascular disease is a leading cause of death in Ontario, with an age-adjusted mortality of 29%.54
To protect against potential immortal-time bias,55
we excluded cardiovascular events between the outbreak and each participant’s index date (enrollment in the Walkerton study).55,56
There was no appreciable difference in the proportion excluded for this reason across comparison groups (1.75% of eligible participants).
As in other outbreak situations, multiple bacteria contaminated the water; Campylobacter jejuni
was also detected, and coinfection occurred. It is possible that exposure misclassification could have attenuated the association, if one exists. However, because the infectious dose of E. coli
O157:H7 is much lower than that of Campylobacter
(10–100 cells v. 500–10 000 cells),1
it is unlikely that a participant with acute gastroenteritis was unexposed to E. coli
It is possible that the apparent protective association between mild illness and cardiovascular disease could have resulted from unmeasured or residual confounding if those who suffered only mild illness after infection with E. coli O157:H7 were selectively healthier than the average individual.
Finally, because of the observational nature of the study, we can only establish the lack of an association and not the lack of a causal relation. Nonetheless, the contamination of Walkerton’s municipal water was a disastrous event in a well-defined population, and we controlled for many confounders using exclusions and statistical adjustments. Additionally, the absence of an elevated risk was consistent across all outcomes; unadjusted hazard ratios were either nonsignificant or less than one. This strongly supports our findings of no increased risk of cardiovascular events or death in this population.
This study provides evidence that the risk of major cardiovascular events was not higher in Walkerton in the decade following the E. coli O157:H7 outbreak. This may be partly explained by active surveillance and treatment for conditions such as hypertension, which may prevent cardiovascular events.