This Vaccine is Quietly Doing Something to Your Heart — Transcript

Full transcript

1. 0:00In 2023, a Stanford researcher by the
2. 0:02name of Pascal Gallacher was looking at
3. 0:04the way that Wales had rolled out their
4. 0:06shingles vaccine a decade earlier, and
5. 0:08he noticed something peculiar. To ration
6. 0:10the limited supply, Welsh health
7. 0:12authorities had drawn a line in the
8. 0:14sand. If you were 79 on September the
9. 0:161st, 2013, you qualified. But if you'd
10. 0:19already turned 80, you didn't. So, two
11. 0:22people born a week apart in the same
12. 0:24town with the same GP and the same risk
13. 0:26factors, but only one could get the
14. 0:27vaccine, the other one never could. And
15. 0:30because Wales had detailed health
16. 0:32records on essentially everyone, you
17. 0:33could follow them up for the next seven
18. 0:35years and see what had happened. That's
19. 0:37about as close to a randomized
20. 0:38controlled trial as you'll ever get
21. 0:40without actually running one. What
22. 0:42Gallacher found in those records was
23. 0:44striking enough that it ended up being
24. 0:46published in the journal Nature and then
25. 0:48replicated in Australia and then Canada.
26. 0:51And earlier this year, it landed him on
27. 0:52the Time 100 list of the most
28. 0:54influential people in health and
29. 0:56medicine. Today's video is about
30. 0:57something newer and in some ways more
31. 1:00unexpected. Because if Gallacher was
32. 1:02right and this vaccine is doing
33. 1:03something helpful to the brain, then the
34. 1:05obvious next question is is it helping
35. 1:07anywhere else? And in the last year,
36. 1:10three separate studies, including one
37. 1:11tracking more than a million people for
38. 1:13up to eight years, have come back with
39. 1:15the same answer. The shingles vaccine is
40. 1:18associated with a substantially lower
41. 1:20risk of heart attacks, strokes, and
42. 1:22heart failure. Now, I covered the
43. 1:24dementia side of his work in detail last
44. 1:26year and I'll link that video below, but
45. 1:28the cardiovascular finding is new. It's
46. 1:30bigger. And the question that I want to
47. 1:31walk you through today is whether this
48. 1:33effect is actually real, because the
49. 1:35headline sounds way too good to be true.
50. 1:37Free heart attack protection from a shot
51. 1:39that you're already being told to get.
52. 1:41That should make every well-trained
53. 1:43skeptic uneasy. So, today I'm going to
54. 1:45walk you through three questions. How
55. 1:47good is the evidence really? What is the
56. 1:48most plausible explanation for the
57. 1:50effect if it isn't a mirage? And then
58. 1:52most importantly, what should you
59. 1:54actually do if you're 50 years or older?
60. 1:56So, if shingles itself can damage your
61. 1:58blood vessels, and it can, then a
62. 2:00vaccine that stops shingles from
63. 2:02reactivating should plausibly do
64. 2:03something to your cardiovascular
65. 2:05outcomes. That's not necessarily a
66. 2:07stretch. So, the shingles virus is a
67. 2:09herpes virus. So, after chicken pox
68. 2:11infection in childhood, it lies dormant
69. 2:13inside your nervous system for the rest
70. 2:15of your life. And then when it
71. 2:16reactivates, which is what causes
72. 2:18shingles, it doesn't just damage the
73. 2:20nerve that it travels down, it can also
74. 2:22affect the walls of blood vessels
75. 2:24triggering inflammation, vascular in
76. 2:26some cases strokes or heart attacks
77. 2:28downstream. So, the question stops being
78. 2:30why would a shingles vaccine touch the
79. 2:32heart? It becomes how big is the effect
80. 2:35and how can the studies that try and
81. 2:36measure it actually be trusted? So,
82. 2:38three observational studies have come
83. 2:40out in quick succession and the
84. 2:41strongest one was led by a team in South
85. 2:43Korea. It was published in the European
86. 2:45Heart Journal and their study followed
87. 2:47more than 1.27 million adults aged 50
88. 2:50and older for a median of 6 years. They
89. 2:53used a statistical technique called a
90. 2:55propensity score overlap weighting to
91. 2:57try and make sure that the vaccinated
92. 2:58and unvaccinated groups looked as
93. 3:00similar as possible at baseline. The
94. 3:02results, those who got the vaccine had a
95. 3:0423% lower risk of cardiovascular events
96. 3:07overall and for heart failure, it was
97. 3:09down at 26%. Major adverse events like
98. 3:12heart attacks, strokes or death from
99. 3:14heart disease, they also were down at
100. 3:1626% and the protective signal lasted for
101. 3:19up to 8 years after vaccination. So,
102. 3:21that's the cleanest piece of evidence
103. 3:22that we have. A million people, 8 years
104. 3:25of follow-up, peer reviewed and the most
105. 3:27important caveat, it was the older live
106. 3:29attenuated version of the vaccine, not
107. 3:31the one that most of you in 2026 would
108. 3:33actually be offered and I'll come back
109. 3:35to that in a moment. The second study
110. 3:37was a systematic review and it pulled
111. 3:39together nine studies. The numbers were
112. 3:41more conservative, but the results
113. 3:43pointed in the same direction. But there
114. 3:45is a problem with all of the data that
115. 3:46we're going through so far and I'm sure
116. 3:48you'll spot it from this third study. It
117. 3:50was a retrospective look at a quarter of
118. 3:52a million US adults with established
119. 3:54cardiovascular disease. The vaccinated
120. 3:57group had a 46% lower risk of major
121. 3:59cardiovascular events in the first year
122. 4:01post vaccination. That sounds enormous
123. 4:04and it should raise eyebrows. That same
124. 4:06study reported a 66% reduction in all
125. 4:09cause deaths in the first year after a
126. 4:11single vaccination. These numbers are
127. 4:13far larger than what is typically seen
128. 4:16with even established cardiovascular
129. 4:18therapies and the 66% mortality figure
130. 4:21isn't just impressive. It's doing
131. 4:22something that the rest of the data
132. 4:24isn't. It's giving the game away and I'm
133. 4:26sure you've already spotted the issue.
134. 4:28The people who choose to get a
135. 4:29non-mandatory vaccine, they're not some
136. 4:31random slice of the population. They're
137. 4:33far more likely to see their GP
138. 4:35regularly. They're more likely to take
139. 4:36their medications. They tend to have a
140. 4:38higher socioeconomic status, lower
141. 4:40smoking rates and better preventive care
142. 4:42engagement across the board. In
143. 4:44epidemiology, this is called a healthy
144. 4:47user bias and it's one of the standard
145. 4:48explanations for any observational study
146. 4:51showing that a vaccine may protect you
147. 4:53against something that the vaccine
148. 4:54wasn't designed for. In the three
149. 4:56studies that I just walked you through,
150. 4:57they all share the same fundamental
151. 4:59weakness. But here is where it gets
152. 5:01interesting because if healthy user bias
153. 5:03was the whole story, you'd expect the
154. 5:05benefit to show up most clearly in the
155. 5:07healthiest people as in the ones whose
156. 5:09baseline behaviors are already driving
157. 5:11the effect. In the Korean study though,
158. 5:13the opposite happened. The people who
159. 5:15benefited the most from vaccination were
160. 5:17the ones with unhealthy baseline
161. 5:19behaviors. So it's hard that with a pure
162. 5:22selection effect. If vaccination is just
163. 5:24a proxy for being healthy, then the
164. 5:26unhealthy subgroup is exactly where
165. 5:27you'd expect the signal to wash out. But
166. 5:30instead, that is where the signal was
167. 5:32strongest. Now this doesn't completely
168. 5:33settle the question. The selection
169. 5:35effects, they can hide inside subgroups.
170. 5:37So the smoker who gets vaccinated may
171. 5:39still be more engaged with the health
172. 5:41care system compared to the smoker who
173. 5:43doesn't. But it does introduce a a of
174. 5:45caution that all we're seeing here is
175. 5:47the healthy user bias. So, to figure out
176. 5:49if we're seeing a true causal
177. 5:50relationship here, we need randomized
178. 5:52control trials, and that is where the
179. 5:54work that put Gilsitzer on the Time 100
180. 5:57magazine comes in. So, remember that
181. 5:59line in the sand with the vaccination
182. 6:01rollout in Wales at the beginning of
183. 6:02this video? Those born before the 2nd of
184. 6:05September, 1933, were never eligible,
185. 6:07but if you were born after, then you
186. 6:09were eligible, and that cutoff did not
187. 6:11care about your healthy behaviors. It
188. 6:13didn't care whether you saw your GP, and
189. 6:15it didn't care if you smoked or
190. 6:17exercised. It cared about a single date
191. 6:20on your birth certificate. And in the
192. 6:21dementia analysis that Gilsitzer's team
193. 6:23published in Nature last year, the
194. 6:25eligibility for the vaccine had produced
195. 6:27a substantial protective effect on
196. 6:29dementia diagnoses. It was about a 20%
197. 6:31relative risk reduction, and I covered
198. 6:33that finding in detail in my video last
199. 6:35year, and again, link is below. Overall,
200. 6:38we have three observational studies all
201. 6:39pointing in the same direction, and the
202. 6:41closest that we'll ever get to a
203. 6:42randomized control trial, again,
204. 6:44pointing in that same direction. Now, I
205. 6:46do have to flag something critical here,
206. 6:48because if I don't, the comments
207. 6:49certainly will. The studies that we've
208. 6:51looked at, they used the older shingles
209. 6:53vaccine called Zostavax. So, that
210. 6:55particular vaccine is a live, weakened
211. 6:57virus. That vaccine has been retired in
212. 6:59most of the world. So, the CDC
213. 7:01guidelines in the US, for instance, they
214. 7:03specify the recombinant vaccine called
215. 7:05Shingrix. Shingrix is a fundamentally
216. 7:07different product. It's just got a piece
217. 7:09of the virus, not the whole thing. So, a
218. 7:11fair question is, do the off-target
219. 7:14benefits seen with the older Zostavax
220. 7:16vaccine, do they carry over to this new
221. 7:18vaccine that's offered today? The honest
222. 7:20answer is probably yes, but our evidence
223. 7:23here is a notch weaker. An Oxford team
224. 7:25used the moment in 2017 when the United
225. 7:28States switched from the older Zostavax
226. 7:30to Shingrix as a quasi-natural
227. 7:32experiment. They compared roughly
228. 7:34100,000 Shingrix recipient to roughly
229. 7:37100,000 Zostavax recipient, matched on
230. 7:40baseline characteristics, and followed
231. 7:42them up for 6 years. Shingrix was
232. 7:44associated with about a 17% more
233. 7:46dementia-free time than Zostavax,
234. 7:49meaning that in the starter set,
235. 7:50Shingrix looked at least as protective
236. 7:52and possibly even more so. Now, two
237. 7:55caveats on this. First, this is an
238. 7:57observational study again, and second,
239. 7:59one of the senior authors has a
240. 8:00consulting relationship with GSK, which
241. 8:03is the manufacturer of Shingrix. Now,
242. 8:05the team says that GSK had no role to
243. 8:07play in the specific study, and I do
244. 8:09take them at their word, but it's the
245. 8:10kind that you should know. So, where to
246. 8:13from here? Well, this is what I advise
247. 8:15my patients. If they're 50 years and
248. 8:16older and they haven't been vaccinated
249. 8:18against shingles, the case for getting
250. 8:20Shingrix has just gotten stronger. The
251. 8:22original reason to try and avoid a
252. 8:24shingles flare-up and prevent painful
253. 8:26and sometimes debilitating rashes and
254. 8:28lingering nerve pain that can follow it
255. 8:29and even blindness, that is a reasonable
256. 8:31one. But the dementia signal added
257. 8:34further weight, and now the
258. 8:35cardiovascular signal adds even more
259. 8:37weight to get the Shingrix vaccine. Now,
260. 8:39one thing that your GP might not
261. 8:41emphasize is that Shingrix, to put it
262. 8:43politely, is a vaccine that you'll feel.
263. 8:45So, the injection site soreness,
264. 8:47fatigue, headaches, and sometimes a
265. 8:48fever, they're common after both doses.
266. 8:51So, roughly one in six recipients had
267. 8:52reactions severe enough to interfere
268. 8:54with their next-day daily activities.
269. 8:56It's not an emergency, it's just the
270. 8:58immune system doing what the adjuvant is
271. 9:00designed to make it do, but it's worth
272. 9:02knowing in advance. So, a practical tip
273. 9:04is to make sure that you have your
274. 9:05vaccines done on a Friday afternoon, so
275. 9:08the worst of the reaction lands on a
276. 9:09Saturday and not during a work week. And
277. 9:12if you've already had the older Zostavax
278. 9:14vaccine years ago, the CDC recommends
279. 9:16getting the two-dose Shingrix course
280. 9:18anyway. Shingrix is more effective at
281. 9:20preventing shingles itself, and the
282. 9:21off-target evidence that we've got for
283. 9:23the recombinant vaccine, it looks at
284. 9:25least as strong. But what I would not
285. 9:27tell my patients is that this is not a
286. 9:28reason to chase down a vaccine that you
287. 9:30might not be eligible for. The
288. 9:32evidence-base is strong enough in my
289. 9:33view to be another reason not to skip
290. 9:35Shingrix when your turn comes along, but
291. 9:38it's not strong enough to recommend
292. 9:39off-label vaccination for 40-year-olds,
293. 9:41for instance. So, there is a real
294. 9:43difference, and I do want to be careful
295. 9:44about it. There's one extra detail about
296. 9:46Goldacre's work that I do want to leave
297. 9:48you with. When he first noticed the
298. 9:50Welsh birthday cutoff in those records,
299. 9:52he wasn't looking for a vaccine that
300. 9:53lowered dementia. He was looking at how
301. 9:55policy decisions get made when supplies
302. 9:58are limited. The dementia finding, it
303. 9:59came as a surprise to him. The
304. 10:01cardiovascular finding came as a
305. 10:03surprise to a different team in Korea
306. 10:05looking at a completely different
307. 10:06population. So, sometimes the most
308. 10:08useful evidence in medicine, it doesn't
309. 10:10come from the trial that it was designed
310. 10:12for. It came from a date on a birth
311. 10:14certificate. And speaking of accidents,
312. 10:16there's a $2 lozenge that by every
313. 10:18randomized controlled trial we have,
314. 10:20beats every cold medicine on the shelf,
315. 10:21and it was discovered by accident in
316. 10:231979. And I cover the evidence in detail
317. 10:26in this next video here.