All About EVA

Vascular ageing describes changes in the structural and mechanical properties of the vascular wall which lead to increased arterial stiffness. Stiffness of the arteries is now recognized not only as a key component of vascular ageing, but as one of the most important structural biomarkers of overall biological age (1).

Arterial stiffening is largely due to endothelial dysfunction, with substantial medial fibrosis and a variable degree of calcification. Reduced compliance in large arteries then exposes smaller vessels to increased down-stream hydraulic and laminar stresses which promote the closure or loss of arterioles and capillaries, altered tissue perfusion and end-organ damage (2).

All of this brings us to EVA, which stands for Early Vascular Aging, and describes arteries that are stiffer than they ‘should’ be at any given age. NVA is normal vascular ageing (shouldn’t it really be NOVA?) and SUPERNOVA is Supernormal (delayed) Vascular Aging.

As diabetes, dyslipidemia, hypertension and likely obesity increase arterial stiffness (3-5), more people are falling out of the SUPERNOVA and NVA categories, and into the EVA sump. Smokers tend to be EVA candidates also (6) – and if you vape, you may still be in trouble (6, 7).

EVA is associated with systolic hypertension, coronary artery disease, stroke, heart failure and atrial fibrillation, which are leading causes of mortality, and is strongly linked with increased risk of cardiovascular disease in general (ie 8-10). NB: The fact that arterial stiffness predicts atrial fibrillation (11) may simply reflect the fact that both conditions are driven by chronic inflammation and fibrosis.

Keeping your arteries elastic for longer seems, therefore, like an excellent idea (8, 9). But how do you do it?

Arterial stiffening involves various sub-routines. These include not only the endothelial dysfunction, medial fibrosis and calcification referred to above but also the degradation and loss of elastin fibers, increased collagen with crosslinking of collagen and other structural fibers, and changes in vascular smooth muscle tone. All of these are driven by interactions between chronic inflammatory (12), glycative (13), carbamylative (14), oxidative (15) and carbonylative (16, 17) stresses, and all of these stresses are encouraged by the modern, industrial diet.

Hypertension is a contributory or at least convergent factor (2, 18), emphasizing yet again the importance of blood pressure control which is, at the population level, poor to very poor (19). And the most important cause of high blood pressure is of course chronic inflammatory stress, aka endothelial dysfunction.

Endotoxaemia driven by colonic dysbiosis appears to be another causative factor of arterial stiffening (20-22), and is another depressingly common feature of modern life, thanks to the murderous behavior of the multinational food companies (23). Downgraded butyrate formation, a result and feature of modern dysbiosis, may play into this (24).

EVA is not routinely measured, so there is little direct epidemiological evidence of trend. However, the increasing numbers of humans with risk factors for EVA (ie 25, 26) surely means that the condition is multiplying, and on course to drag our appalling public health down still further.

Once arterial stiffening has developed, increased hydrodynamic stress feeds back to the heart, compromising and damaging the myocardium, and forward to the capillary beds, causing particular damage in highly perfused tissues such as the brain and the kidneys.

There is a nasty feedback loop here. Chronic kidney disease promotes vascular ageing, makes arterial stiffness worse (27) and appears to accelerate multiple aspects of the ageing process (28, 29). Increased protein denaturation in vessel walls (via uricaemia and increased carbamylative stress) is likely involved in this loop. Diabetes is somewhat similar to CKD in that it also increases ageing, protein denaturation and cross-linkage, but predominantly via increased glycative stress (30, 31).

No need, however, for therapeutic fatalism.

Vascular micro- and macro-anatomy is a regionally specialized part of the extra-cellular matrix, and as such can potentially be rehabilitated; the ECM is a dynamic tissue which continuously undergoes controlled remodeling in response to changing demands (32). Even the long-lived structural proteins in vessel walls turn over, albeit slowly; and in a less destructive milieu, will eventually be replaced by less damaged and more elastic components (33, 34, 55).

If our focus is on public health, and we want to shift the population from EVA towards NVA and then SUPERNOVA, this has to start with reducing the burden of obesity, hypertension, diabetes and chronic kidney disease. This means substantial changes in diet and lifestyle for the many, and will require coherent support and leadership from industry and government.

Not going to happen.

From Aurelien, a subtle and creative thinker who knows the system from the inside: ‘Sadly, the problem with the system is less that it won’t change, than it cannot change. Its leaders are not very bright, they are saturated with their own ideology, and are so incompetent that if they did miraculously understand the need for change, it would be impossible for them to use the enfeebled machinery that remains to actually get anything done.’ (35 and, for those interested in such things, 36).

Some major players in the food space are starting to think about producing genuinely functional and vaso-protective foods. However, product development, regulatory wrangling and market strategizing will all take time.

In the meantime, for those with a personal interest in going Supernova, the path is quick and easy. Examples have already been set; from the elastic-sided Tsimane of Bolivia (37), who have very little cardiovascular disease, to the only slightly less exotic survivors of the Leningrad siege (38, 39).

The Tsimane consume a high nutrient-density, anti-inflammatory and fiber-rich diet and engage in high levels of physical activity, a lifestyle which ensures a near-absence of obesity, diabetes, hypertension and arterial calcification (ie 40, 41). Their arteries are up to 86% more elastic than their more rigid US counterparts (37), which goes some way to explaining why they are so much less likely to dement (42, 43).

The Leningrad papers (38, 39) describe now elderly subjects who experienced severe calorie restriction very early in life, during the period September 1942 to January 1944. This kind of calorie restriction has long been associated with prolongation of life span (in survivors), and epigenetic changes in vascular responsiveness to stress now emerge as a likely component in that prolongation.

It is worth noting that the individuals highlighted in the Leningrad report (38) consumed very little ultra-processed foods – and, taking all the above factors into account, one can assemble a roadmap to joining the ranks of the SUPERNOVA family.

1. Minimize your intake of ultra-processed foods, a general food category strongly linked to diabetes (44), cardiovascular disease (45), hypertension (46), death (47) and other negative outcomes.
2. Minimize your intake of sugars and refined digestible starch (48, 49), use a proven anti-inflammatory regime (47), maintain eubiosis (20-22) and good hydration (50). Switch from table salt to PanSalt (51) or my second choice, GoodSalt (52), proven anti-hypertensive salt substitutes (52).
3. Mind your microbes. The colonic microbiota is deeply implicated in the regulation of arterial stiffness (34), and should be fed with prebiotic fibers and polyphenols (34, 54).
4. Add nutrients which directly reduce cross-link formation and therefore arterial stiffness, such as the polyphenol rosemarinic acid (55). This interesting phytonutrient occurs in lemon balm, rosemary, sage, oregano, thyme and peppermint.
5. In obese subjects, calorie restriction and weight loss are likely to help increase arterial elasticity (56, 57). In diabetics, normalizing blood sugar (preferably via diet and exercise) will pay dividends (567 58).
6. Consider EVOO. The Mediterranean diet is linked to delayed vascular ageing (ie 59) and high polyphenol Extra-Virgin Olive Oil, an important constituent in the Med diet, has vaso-protective properties (ie 60). NB This last paper showed that EVOO lowered systolic blood pressure but the duration of dosing, at a mere three weeks, was in my view insufficient to alter arterial compliance.

Finally, the mechanisms which degrade arterial elasticity are broadly similar to those which contribute to ageing of other tissues such as skin. Conversely, a regime designed to push you from EVA up into the Supernova category will also tend to increase the elasticity of your skin. You might therefore be able to measure increased elasticity not only by checking your blood pressure, but also via the skin pinch test.

You may even see it in the mirror.

Next week: The Outer Limits.

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