Arteries are not rigid pipes. They respond to blood pressure, metabolism, inflammatory processes and the composition of the blood. The blood vessel wall therefore also changes with increasing age. One of the most important changes is arteriosclerosis, in which the structure of the arteries changes over years and so-called plaques can form in the blood vessel wall.
For a long time, arteriosclerosis was understood primarily as a build-up of cholesterol. Today, the picture is much more complex. Important factors include the amount of atherogenic lipoproteins in the blood, their deposition in the blood vessel wall, immune responses and chronic inflammatory processes. High blood pressure, smoking, diabetes, lack of exercise and genetic factors also influence its development.
What is particularly relevant is not only whether a change in a blood vessel has already developed, but also how long the vessels are exposed to certain stresses. This is precisely where an important connection to longevity lies: vascular health is closely linked to the long-term health of the entire organism.
Contents
- What arteriosclerosis actually is
- How a plaque forms in an artery
- The role of LDL cholesterol and other lipoproteins
- Why inflammation drives arteriosclerosis
- Which risk factors influence vascular health
- Arteriosclerosis and healthy ageing
- What can be influenced in everyday life
- How arteriosclerosis is detected and treated
- What research still does not fully understand today
- References
What arteriosclerosis actually is
Arteriosclerosis describes a structural change in the artery wall. It is often referred to colloquially as ‘hardening of the arteries’. However, the term is somewhat misleading, because arteriosclerosis is much more than calcification.
In its most common form, atherosclerosis, cholesterol-containing and other atherogenic lipoproteins accumulate in the inner layer of the artery wall. This is followed by complex responses involving immune cells, connective tissue cells and cells of the blood vessel wall. Over time, an atherosclerotic plaque can develop.
Plaques may initially change the vessel without severely restricting blood flow. Problems arise particularly when a plaque becomes unstable and ruptures. A blood clot can then form on its surface. Depending on where this happens, the result may be a heart attack, an ischaemic stroke or impaired circulation in other organs.
Atherosclerosis does not only affect the coronary arteries. In principle, it can occur in various medium-sized and large arteries. Coronary heart disease, peripheral arterial disease and certain forms of ischaemic stroke therefore belong to the spectrum of atherosclerotic diseases.
Arteriosclerosis is a long-term process
An important finding of modern vascular research is that atherosclerosis does not suddenly begin in older age. Initial changes can develop early in life. However, how quickly they progress and whether they eventually lead to clinically significant disease depends on many factors.
This makes the disease a particularly good example of why cumulative exposure plays a role in healthy ageing. LDL cholesterol elevated over decades, persistently high blood pressure or many years of smoking do not act independently of one another. They can reinforce one another and place stress on the blood vessel wall over a long period.
How a plaque forms in an artery
In simplified terms, the formation of an atherosclerotic plaque can be understood as an interplay between lipoproteins, the blood vessel wall and the immune system.
The inner surface of an artery is lined by the endothelium. This thin layer of cells regulates exchange between the blood and the blood vessel wall, among other functions, and responds to mechanical and chemical signals. When the endothelium is exposed to certain stresses, its behaviour can change.
A central role is played by the deposition of ApoB-containing lipoproteins in the blood vessel wall. These include LDL, VLDL remnants and lipoprotein(a). The more of these particles are present in the blood and the longer the blood vessel wall is exposed to them, the greater the likelihood that particles will be retained in the artery wall.
There, immune cells recognise them. Monocytes migrate into the tissue and develop into macrophages. These take up altered lipids and can develop into so-called foam cells. At the same time, further signalling substances are released that promote a local immune response.
Early fat accumulations can develop into complex plaques over time. They contain lipids, immune cells, connective tissue and cellular debris, among other components. In advanced plaques, a so-called necrotic core can develop.
At the same time, the blood vessel wall tries to control the increasing stress. Smooth muscle cells can migrate into the plaque and form connective tissue structures. This can produce a fibrous cap that separates the lipid-rich area from the bloodstream.
This explains an important distinction: Not every plaque is equally dangerous. What matters is not only its size, but also its composition and stability.
The role of LDL cholesterol and other lipoproteins
Few factors are as important for understanding atherosclerosis as LDL cholesterol. LDL, short for Low Density Lipoprotein, transports cholesterol in the blood. Cholesterol itself is essential to the body, including as a component of cell membranes and as a starting material for certain hormones.
A persistently elevated supply of atherogenic lipoproteins in the blood becomes problematic. The scientific evidence for this is unusually extensive. Genetic investigations, observational studies and randomised clinical trials independently conclude that LDL plays a causal role in the development of atherosclerotic cardiovascular disease.
This is not solely about the amount of cholesterol. The number of particles transporting cholesterol and other lipids into the blood vessel wall is also crucial. ApoB is a structural protein of these particles and can therefore serve as an approximate measure of the number of atherogenic lipoprotein particles.
Why the duration of exposure matters
With LDL, it is not only the current blood value that is relevant. The duration of exposure also plays a role.
Someone with elevated LDL values over many years experiences greater cumulative exposure of the artery wall than someone whose values are lower for most of their life. Genetic studies support this concept particularly clearly.
This does not mean that a single cholesterol value determines an individual's fate. Cardiovascular risk arises from the interplay of various factors. Nevertheless, cumulative LDL exposure explains why vascular health early in life is relevant to long-term prevention.
Not all cholesterol should be assessed in the same way
Other lipoproteins play a role alongside LDL. These include triglyceride-rich remnant lipoproteins and lipoprotein(a), or Lp(a) for short.
Lipoprotein(a) is particularly interesting because its concentration is largely genetically determined and elevated values are associated with a higher risk of atherosclerotic cardiovascular disease. Unlike LDL, Lp(a) changes comparatively little over the course of life in most people.
The European Atherosclerosis Society therefore regards elevated Lp(a) concentrations as a relevant additional risk factor. At the same time, it is important to interpret the current evidence correctly: although a causal relationship between Lp(a) and cardiovascular disease is well established, the direct clinical benefit of specifically lowering Lp(a) is still being investigated.
Why inflammation drives arteriosclerosis
Cholesterol alone does not explain atherosclerosis. Today, it is regarded as a chronic inflammatory process in the blood vessel wall.
As soon as atherogenic lipoproteins accumulate in the tissue, cells of the innate and later also the adaptive immune system respond. Macrophages, T cells and other immune cells influence plaque development. Numerous messenger substances are released in the process, which can sustain inflammatory processes.
The CANTOS study provides a particularly illustrative example. This randomised clinical trial examined people who had already suffered a heart attack and continued to have elevated levels of the inflammatory marker hsCRP. Canakinumab was used to specifically block the interleukin-1β signalling pathway.
The study showed that targeted inhibition of inflammation could reduce cardiovascular events, even though canakinumab did not lower LDL concentrations. At the same time, significant side effects occurred. The results therefore did not demonstrate that general suppression of the immune system would be useful. Rather, they showed that inflammation itself is a biologically relevant part of atherosclerosis.
This was an important step for research. The disease cannot be understood solely as a problem of fat metabolism.
When a plaque becomes unstable
A plaque can remain relatively stable for years. A particularly dangerous change occurs when the protective fibrous cap becomes thinner and more vulnerable.
Immune cells activated by inflammation can release enzymes that break down components of connective tissue. This can reduce plaque stability. If the surface ruptures, the blood comes into contact with thrombogenic components of the plaque. Clotting is activated and a thrombus can form.
In this way, a previously perhaps unremarkable change in a blood vessel can lead to an acute blockage within a short time.
This also explains why simply measuring a narrowing of a blood vessel does not reflect the entire risk. Plaque stability and inflammatory activity are also relevant.
Which risk factors influence vascular health
Atherosclerosis has no single cause. Rather, it arises from the interplay of genetic predisposition, age, metabolism, blood pressure, lifestyle and other biological factors.
The most important modifiable factors include:
- elevated concentrations of atherogenic lipoproteins
- high blood pressure
- smoking
- diabetes and impaired glucose metabolism
- lack of exercise
- excess weight and, in particular, poor metabolic health
- certain dietary habits
- chronic kidney disease
There are also factors that cannot be influenced, or can only be influenced to a limited extent. These include age and genetic predisposition. Familial forms of markedly elevated LDL values can also significantly alter the risk.
High blood pressure
High blood pressure places mechanical stress on the blood vessel wall. The endothelium is continuously exposed to higher pressure forces, while the structure of the arteries can also change.
Current European guidelines consider the relationship between blood pressure and cardiovascular risk to be continuous. There is therefore not merely an abrupt transition between ‘healthy’ and ‘ill’. As blood pressure exposure increases and persists for longer, cardiovascular risk also changes.
Smoking
Tobacco smoke affects blood vessels on several levels. It can promote oxidative stress and inflammatory processes, impair endothelial function and influence blood clotting.
Smoking is therefore not merely an additional risk factor alongside cholesterol and blood pressure. It can alter various biological processes simultaneously.
Diabetes and metabolism
Persistently impaired glucose metabolism also affects vascular health. In diabetes, several unfavourable factors often occur together, including elevated glucose values, changes in lipid metabolism, high blood pressure and chronic inflammatory processes.
Research shows that diabetes can intensify certain mechanisms of atherosclerosis. These include changes in the blood vessel wall, oxidative stress and an altered immune response.
This helps explain why metabolic health is so relevant to vascular health.
Arteriosclerosis and healthy ageing
The cardiovascular system is one of the biological systems in which ageing processes become particularly apparent. With increasing age, vascular stiffness, endothelial function, mitochondrial function and immune regulation change, among other things.
Current research into the Hallmarks of Cardiovascular Aging describes several interconnected processes, including mitochondrial dysfunction, cellular senescence, changes in autophagy, epigenetic changes and chronic inflammatory processes.
Atherosclerosis cannot simply be equated with normal ageing. Age is a risk factor, but not an inevitable diagnosis. What matters is how strongly additional stresses affect the blood vessels and how individual genetic and biological factors take effect.
The connection between atherosclerosis and the so-called inflammaging hypothesis is particularly interesting. This describes the age-related shift of the immune system towards a more chronically inflammatory state. Inflammatory processes can in turn influence vascular ageing and plaque development.
Mitochondrial function also plays a role. Mitochondria supply energy to cells and are also involved in regulating oxidative stress and cellular signalling pathways. Changes in mitochondrial function can therefore influence the resilience of vascular cells.
Research is increasingly trying to consider these processes together. Vascular ageing is an interplay between different biological systems that extends far beyond cholesterol alone.
What can be influenced in everyday life
People who want to support their vascular health over the long term do not need a single ‘anti-arteriosclerosis measure’. It is more useful to keep the most important modifiable risk factors in view.
Exercise
Regular physical activity influences several factors simultaneously. Among other things, it affects blood pressure, glucose metabolism, physical fitness and body weight.
Exercise does not always have to involve intensive training. The first priority is to integrate regular activity into everyday life. Strength training can be a useful addition, particularly because muscle mass and physical performance play an important role in general health with increasing age.
Diet
For vascular health, the overall dietary pattern matters more than a single ‘superfood’ ingredient.
A diet high in vegetables, fruit, wholegrain products, pulses, nuts and unsaturated fatty acids fits the dietary patterns frequently recommended for cardiovascular prevention.
At the same time, it is worth looking at the quality of fats. A high proportion of saturated fatty acids can contribute to higher LDL values in some people. However, the effect depends on the overall dietary pattern and what replaces the saturated fatty acids.
Know your blood pressure and blood sugar
High blood pressure often causes no clear symptoms for a long time. Occasional checks can therefore be useful, particularly if other risk factors are present.
The same applies to metabolism. Blood glucose and HbA1c can provide clues about how glucose metabolism functions over the long term.
Do not judge cholesterol solely by how you feel
A healthy lifestyle is important, but does not replace an individual medical risk assessment. A closer look can be useful particularly with significantly elevated LDL cholesterol or a family history.
Depending on the personal situation, alongside LDL-C, ApoB and Lp(a) can also provide additional information. Which values are actually useful depends on the individual risk profile.
Smoking
For smoking, the conclusion is comparatively clear: stopping smoking is one of the most important modifiable measures for cardiovascular health.
Here too, it is not about a single mechanism. Avoiding tobacco reduces a whole range of stresses on blood vessels, blood clotting and metabolism.
How arteriosclerosis is detected and treated
Atherosclerosis can exist for years without typical symptoms. A diagnosis is therefore not made on the basis of a single symptom alone.
An individual assessment begins with medical history and known risk factors. Depending on the situation, blood pressure, blood lipids, glucose metabolism and other laboratory values are examined.
Imaging methods can provide additional information for certain questions. These include ultrasound examinations of the carotid arteries or methods for assessing blood vessels and coronary calcium. However, such investigations are not automatically useful for every healthy person. Their significance depends on the specific question and the individual's baseline risk.
When treatment becomes necessary
Treatment depends on which disease is already present and how high the individual risk is.
A central approach is to lower atherogenic lipoproteins. Statins are among the best-studied medicines for this purpose. Depending on the starting situation, other active substances such as ezetimibe or PCSK9 inhibitors may be used.
The importance of consistent LDL reduction is illustrated by the FOURIER study, among others. In this randomised study of more than 27,000 people with existing atherosclerotic cardiovascular disease, additional treatment with the PCSK9 inhibitor evolocumab led to a marked reduction in LDL cholesterol and fewer cardiovascular events.
Such studies are important because they show that LDL is not merely a marker that occurs alongside atherosclerosis. Targeted changes in LDL levels can influence the clinical course.
However, which treatment is appropriate in an individual case depends on factors such as age, existing disease, baseline LDL value, family history and overall cardiovascular risk.
What research still does not fully understand today
The basic principles of atherosclerosis are now well understood. At the same time, numerous questions remain open.
One concerns the individual susceptibility of the blood vessel wall. Two people can have similar LDL values yet develop vascular changes of different severity. Genetic factors, immune responses, lipoprotein composition and properties of the blood vessel wall could play a role.
Researchers are also studying how plaques can be specifically stabilised or made to regress. Imaging studies show that intensive lowering of atherogenic lipoproteins can beneficially alter plaque burden and composition. However, complete regression is not the aim of every treatment and cannot be expected for every plaque.
Another area of research concerns the immunobiology of atherosclerosis. The immune system does not merely respond to deposited lipids; it can actively influence further plaque development. New research approaches therefore examine immune cells, inflammatory signalling pathways and communication between the blood vessel wall and the immune system.
The connection to biological ageing is also increasingly being investigated. Senescent cells, mitochondrial changes, epigenetic processes and chronic inflammation could influence one another. However, which of these processes actually represent the most important targets for future treatments in humans has not yet been conclusively established.
What matters is not a single value
Atherosclerosis is not a condition that can be reduced to a cholesterol value, a blood pressure value or a single biomarker.
Individual risk arises from an interplay between time, lipoproteins, blood pressure, metabolism, inflammation, genetics and lifestyle. This is precisely why the long-term perspective is so important.
For healthy ageing, this means above all taking vascular health seriously before symptoms appear. Many relevant processes begin long before clinically recognisable disease. At the same time, a single laboratory value cannot tell us how a person's blood vessels will develop.
Modern atherosclerosis research therefore paints a nuanced picture: the disease is complex, but some of its central drivers have been studied very thoroughly. Long-term exposure to atherogenic lipoproteins in particular is among the most strongly established factors. Together with blood pressure control, not smoking, regular exercise and an overall favourable metabolic state, this provides an approach focused on the long-term maintenance of vascular health rather than a single health hack.
References
- Borén, J., Chapman, M. J., Krauss, R. M. et al. (2020). Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 41(24), 2313–2330.
- Ference, B. A., Ginsberg, H. N., Graham, I. et al. (2017). Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 38(32), 2459–2472.
- Döring, Y., van der Vorst, E. P. C., Weber, C. (2024). Targeting immune cell recruitment in atherosclerosis. Nature Reviews Cardiology, 21, 824–840.
- Baumer, Y., Irei, J., Boisvert, W. A. (2025). Cholesterol crystals in the pathogenesis of atherosclerosis. Nature Reviews Cardiology, 22, 315–332.
- Khan, A., Roy, P., Ley, K. (2024). Breaking tolerance: the autoimmune aspect of atherosclerosis. Nature Reviews Immunology, 24, 670–679.
- Abdellatif, M., Rainer, P. P., Sedej, S., Kroemer, G. (2023). Hallmarks of cardiovascular ageing. Nature Reviews Cardiology, 20, 754–777.
- Sarraju, A., Nissen, S. E. (2024). Atherosclerotic plaque stabilization and regression: a review of clinical evidence. Nature Reviews Cardiology, 21, 487–497.
- Ridker, P. M., Everett, B. M., Thuren, T. et al. (2017). Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine, 377, 1119–1131.
- Sabatine, M. S., Giugliano, R. P., Keech, A. C. et al. (2017). Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine, 376, 1713–1722.
- Kronenberg, F., Mora, S., Stroes, E. S. G. et al. (2022). Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal, 43(39), 3925–3946.
- Visseren, F. L. J., Mach, F., Smulders, Y. M. et al. (2021). 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 42(34), 3227–3337.
- McEvoy, J. W., McCarthy, C. P., Bruno, R. M. et al. (2024). 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. European Heart Journal, 45(38), 3912–4018.
- Khan, A. W., Jandeleit-Dahm, K. A. M. (2025). Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches. Nature Reviews Cardiology, 22, 482–496.
More articles
Matching products
