Notice that the references frame inflammation as exacerbating or contributory to ASCVD but more as an accelerant and not necessary to as part of the causal chain. It think it may be causal. The evidence is thin because few studies have examined this specific question and generally not thoroughly. Correlational examinations tend to show that inflammation is a significant accelerant in ASCVD. Several studies suggest that only ~20% of significant ASCVD events occur in patients with low inflammation. However when you examine the studies, you see a high level set for the “low inflammation” binary and you see that the classification was made on the basis of a single marker; e.g., CRP<0.10. The is contrary case evidence is interesting. Some individuals identified with exceptionally high levels of destructive lipids have normal arteries and no ASCVD but are distinctive for their very low levels of inflammation. At least one other study obtained better results with an ASCVD population by lowering inflammation than by lowering targeted lipids. My view at the moment is that if your MPO and Lp-PLA2 values are in the lowest decile, your lipid profile, including Lo(a) is virtually irrelevant to the consideration of whether you will develop atherosclerosis. You will not. It remains a step of some distance from there to finding that we would be better off eliminating the sources of arterial inflammation than managing serum lipids and yet another step to concluding that such a strategy could result in the regression of some forms of existing arterial disease.
I think in fact the key interleukin is il-10 which is part of SASP, but is considered anti-inflammatory. However, there is evidence that it causes senescence and AIUI that is through a reduction in the expression of SLC25A1 via NF kappa B. (reduction) operating through the Janus Kinase.
So the link between air pollution and mortality has been known for 70 years. About as long as smoking.
The latest reference I have is from MIT and states that 200,000 premature deaths annually in the US from air pollution. Many of these are from CVD and the point is that these deaths occur earlier but presumably would have happened anyway - just 10 years later (on average).
Radon is responsible for 21,000 US cases annually and presumably many of those don’t die even if most do.
Now radon may also contribute to early death from other things but lung cancer is the only thing I ever hear about.
So I agree with Claude on the ranking but not sure that Radon is the main issue. We have air purifiers in all the bedrooms. My city is slightly above US average on PM2.5.
Right. It is a little ambiguous but I took Claude’s reference to radon to apply to indoor pollution as a particularity. At a time when so many people smoked, I would guess the reference would be to second hand smoking, etc. One breakout on attributions is:
The primary contributors are road transportation, responsible for roughly 53,000 deaths, followed closely by electric power generation, which accounts for about 52,000 deaths.
Other significant sources include industrial activities, contributing approximately 41,000 deaths, and commercial and residential sources (such as commercial solvents, heating, and in home cooking), which cause deaths primarily in densely populated coastal regions. Smaller but notable contributions come from marine transportation, particularly in Southern California (approx. 3,500 deaths), and rail transportation, which has a comparatively slight and uniformly distributed impact. Per capita, I would guess, radon will show great regional variations ranging from very high to virtually non-existent. I have dealt with radon in several homes and had many others where radon was measured only at the background level for the elevation, etc.
- Air pollution is now the second leading risk factor for death worldwide behind high blood pressure, and ahead of tobacco and poor diet.
This is not even cutting edge stuff. Here’s a paper from 2010:
https://www.ahajournals.org/doi/10.1161/cir.0b013e3181dbece1
PM2.5 causes systemic oxidative stress, endothelial dysfunction, autonomic imbalance, and low-grade vascular inflammation
And aside from death, around 30% of childhood asthma is attributable to car exhaust NO2.
Up to 23 million annual asthma emergency room visits globally are attributable to ozone, and 5–10 million attributable to PM2.5.
And for cancer, PM2.5 was formally classified as a Group 1 human carcinogen way back in 2013. 370,000–450,000 lung cancer deaths per year are due to PM2.5, which is about 15–20% of global lung cancer mortality.
And more worryingly, https://pubmed.ncbi.nlm.nih.gov/37020004/ showed that PM2.5 promotes EGFR-mutant lung adenocarcinoma in never-smokers. It can explain around 15% of the lung cancers in never-smokers.
There are also links to diabetes: https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30140-2/fulltext That’s a paper about data from 2016, showing ~3.2 million T2D cases per year are attributable to PM2.5.
For kids, air pollution is associated with 2.7–3.4 million preterm births per year, and ~16% of low-birth-weight infants globally (https://www.sciencedirect.com/science/article/pii/S0013935123024416)
I suppose as somebody interested in longevity, you’re worried about dementia. Well https://www.bmj.com/content/381/bmj-2022-071620 showed that every 2 μg/m³ long-term PM2.5 increases all-cause dementia with a HR of ~1.04.
The evidence seems to weigh air pollution much more strongly than those. And especially water. If you live in a first-world country, your water is just fine. I asked Claude to integrate the findings, and it reckons that total deaths from chemicals in drinking water (lead, arsenic, PFAS etc) are responsible for 3-5% as many deaths as air pollution. Even if you take in total unsafe water (like bacterial contamination, poor sewerage etc), then it would be 20% of air pollution.
It also gives a nice explanation:
Dose and duration. You inhale ~11,000 liters of air per day versus ~2 liters of water. Even at modest PM2.5 concentrations, total delivered dose of particles and adsorbed toxicants to the alveolar surface is enormous, and the alveolar–capillary barrier is ~0.5 μm thick with no first-pass metabolism. Ingested chemicals pass through gut epithelium plus hepatic first-pass clearance, and most are excreted.
We can actually do some basic maths:
- Resting/sleeping adult: ~5–6 L/min
- Light activity (sitting, light office work): ~12 L/min
- Moderate activity (walking, housework): ~25 L/min
- Heavy activity (running, cycling): ~50–80 L/min
So let’s use 15 L/min as a representative number. Based on USA average levels of 9µg/m^3, it means yearly exposure of ~50mg/year. If you live in Dehli, that is 500mg/year.
During a wildfire, PM2.5 levels can rise to 300µg/m3, which will give you 4.5mg per day
The particles are tiny and don’t weigh much, so a better way might be to think about particle number. In the USA, that would be 10¹¹ to 10¹² ultrafine particles per day deep into your lungs.
low dose naltrexone would be my go to here