Stroke vs Flu Jab Study - Wrap-Up

Diving to the bottom of the subject crosses all Ts.

Contunied from “Worried About Stroke? Don't Rush to Get Your Flu Shot Just Yet...”

The reader Steve River raised a possibility that the stroke data from the UCalgary study “Association between influenza vaccination and risk of stroke in Alberta, Canada: a population-based study”(Lancet Public Health, November 2022) may be really that bad for the flu-jabbed, but after adjusting for this or that, the reality may, in fact, be the exact opposite. How could that be?

For example, if the high-risk group for stroke gets flu shots and those that are not don’t. One such prominent case may be age, or whether one lives in rural or urban areas. Like old folks homes tend to be in urban areas. Surprisingly, the study authors from the UCalgary say:

We found effect modification by each covariate examined except for home location; however, vaccination was associated with a reduced risk of stroke overall across all ages and risk profiles with the exception of individuals without hypertension.

So, we can rule out my two hunches above, as the authors claim age-stratified effects, and no matter the old folks homes or otherwise. So what is it?

Don’t forget (and it’ missing from the study title) that the study only concerned itself with the incidence of stroke within 182 days after a flu shot:

Individuals were considered to be exposed to the influenza vaccination for the 182 days (6 months) following vaccination

Would the seasonality of stroke events and the strong seasonality of the flu vaccination drives explain the study results? Like, if most Albertans get their flu shots followed by six months of seasonally lower overall stroke incidence, compared to the other six months of a year, the study would obtain an appearance of flu jabs greatly reducing the incidence of stroke in six months after the jab. I have some evidence to the seasonality of stroke events in Finland, “Seasonality of stroke in Finland”(AnnMed, 2017):

The lowest seasonal admission rates were detected in summer and the highest in autumn for all stroke subtypes. Seasonal variation of IS was more pronounced in men (p = 0.020), while no sex difference was detected in ICH or SAH. The seasonal patterns of in-hospital mortality and length of stay (LOS) differed markedly by stroke subtype. Diagnoses of hypertension, atrial fibrillation, or diabetes showed no seasonality.

But few studies from the US and the UK (references 18-20 in the Finnish study) say that no such seasonal variation is present there. E.g., “Is stroke incidence related to season or temperature? The Oxfordshire Community Stroke Project” (Lancet, 1996):

The widely reported winter excess of ischaemic strokes may be an artifact due to referral bias in hospital-based studies and increased case fatality during the winter in mortality studies.

So, the seasonality doesn’t seem to be the deciding factor here, as much as I wished to be right. But then I noticed this information in the Finnish study:

The classical risk factors of stroke, such as higher age, sex, smoking, and hypertension are well established, but factors that trigger acute stroke have been studied less. Alcohol abuse and infections are the best known stroke triggers.

Bingo! The flu-jabbed lower their incidence of respiratory infection, hence fewer strokes get triggered by flu among the flu-jabbed for some time post jab, compared to the stroke-prone flu-unjabbed. And if one only looks at 182 days after a flu jab, one logically concludes that flu jabs lower the risk of stroke, in that period! That period being the flu season, making the comparison between the flu-jabbed and flu-unjabbed most favourable for the jabbed. But don’t look at what happens to the flu-jabbed in the other six months of the year. Oh, wait, we already know that: the flu-jabbed get so stroke-stricken in the other six months that they are 2.4 times more stroke-prone than the never-flu-jabbed, over the complete 12 months period. For this to take place, it seems like the stroke-prone unvaccinated really have their strokes triggered by flu, in the flu season, but that causes the survivourship bias for the rest of the year where the unvaccinated don’t get strokes NEARLY as much as the flu-jabbed, because whoever among the unvaccinated had to have a stroke, had it already during the past winter’s flu season.

Therefore, avoiding the flu as a trigger of stroke does nothing, overall, to one's odds of getting a stroke - if not this trigger then another will eventually break the camel’s back, so to say, and the underlying vascular system state will lead to a stoke sooner than later. Do we have a case of long-term pain for short term gain? As, by short-term lowering the odds of a bad flu triggering stroke, one puts up with the long-term worse, more brittle, state of one’s vasculature, as examplified by the flu-jabbed’s 2.4 higher propensity for strokes?

And what is this about?

After adjusting for comorbidities, vaccination was strongly associated with a reduced risk of stroke in patients with hypertension; however, there was a non-intuitive interaction, contrasting with previous studies, such that vaccination in patients without hypertension was associated with a marginally higher risk of stroke compared with no vaccination.

We observed that the non-hypertensive vaccinated population was much more likely to be female, and that the young average age of the non-hypertensive never-vaccinated stratum was associated with a small number of outcomes.

Let me offer a inconvenient hypothesis here: as the relatively young and healthy population, absent of the greatest risk of stroke, suddenly becomes more prone to stroke after the flu jab, albeit at a low clip, maybe it’s the effect of the jab? As they start getting a stroke where there was none to begin with? This small safety signal being drowned out by the sheer level of strokes in the more vulnerable populations, jabbed or not. Like what we’ve learned from the Covid jabs, for example? “No, THESE jabs ARE safe!” Would you bet your house on it?

So, the reader Steve River was correct that depending on how you slice your study inputs, you might get the conflicting results. The trick that UCalgary pulled out of their sleeve was them looking only at 182 after a flu shot to make a conclusion about flu shots reducing the odds of stoke:

…crude observation was confounded. Adjusted for age, sex, comorbid illness, and socioeconomic status, recent vaccination (within 182 days) was associated with a reduced hazard of stroke (hazard ratio [HR] 0·775 [95% CI 0·757–0·793]).

Crude observation indeed.