[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Blood vessels](https://durgical.com/en/general-pathology/areas/vessels/) › Atherosclerosis: risk factors

# Atherosclerosis: risk factors

- Topic

Age, sex and genes cannot be changed; cholesterol, blood pressure, smoking and diabetes can, and together they explain most heart attacks.

Updated Nov 12, 2026

## Key points

- Big four modifiable risks: high LDL, hypertension, smoking, diabetes; two together roughly quadruple risk.
- Familial hypercholesterolemia (LDL receptor mutations) shows how LDL alone can cause early coronary disease.
- HDL is protective; high triglyceride-rich lipoproteins add risk.
- High-sensitivity C-reactive protein is a marker of risk, not a proven cause.
- Lipoprotein(a) is genetically set and independently raises coronary and aortic-valve risk.
- Clonal hematopoiesis of indeterminate potential (TET2, DNMT3A mutations in blood cells) raises atherosclerotic risk.

## What it is

Atherosclerosis comes from the sum of many risk factors, and they multiply rather than add. Constitutional factors are age, male sex (until menopause narrows the gap) and family history. The four major modifiable factors are high LDL cholesterol, hypertension, cigarette smoking and diabetes. Inflammation (measured by C-reactive protein), lipoprotein(a), metabolic syndrome, inactivity, stress, high homocysteine and clonal hematopoiesis add further risk.

## Atherosclerosis risk factors grouped by how they act

| Factor | Type | How it promotes plaque |
| --- | --- | --- |
| Age and male sex | Constitutional | Longer exposure; estrogen delays disease in women until menopause |
| Family history and genes | Constitutional | Polygenic risk and single-gene lipid disorders |
| [High LDL cholesterol](https://durgical.com/en/conditions/atherosclerosis-and-dyslipidaemia/) | Modifiable | LDL enters and is trapped and oxidised in the intima |
| [Hypertension](https://durgical.com/en/conditions/arterial-hypertension/) | Modifiable | Shear and pressure injure endothelium; promotes hypertrophy |
| Cigarette smoking | Modifiable | Oxidants, endothelial dysfunction, prothrombotic state |
| [Diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) | Modifiable | Hyperglycemia and advanced glycation end products, dyslipidemia |
| Inflammation (high CRP) | Additional | Marks active vascular inflammation |
| Lipoprotein(a), homocysteine, metabolic syndrome, inactivity | Additional | Pro-thrombotic and pro-atherogenic effects |

## Clinical notes

- Risk calculators combine these factors to decide on prevention; a single high factor in a young person points to a genetic disorder.
- In Colombia and Latin America, hypertension, obesity and diabetes are rising and drive most cardiovascular deaths.

## Memory aid

The four horsemen of the plaque are LDL, pressure, smoke and sugar; they ride together and their damage multiplies.

## Test yourself

Think of the answer, then tap the question to see it.

## What are the four major modifiable risk factors for atherosclerosis?

High LDL cholesterol (hyperlipidemia), hypertension, cigarette smoking and diabetes mellitus.

## Is C-reactive protein a cause of atherosclerosis?

No; it is a strong independent marker of risk that reflects vascular inflammation, but it is not proven to cause plaque.

## Which genetic disorder of the LDL receptor causes coronary disease in youth?

Familial hypercholesterolemia.

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## Elsewhere in DurgiPedia

- [LDL (low-density lipoprotein)](https://durgical.com/en/biochemistry/topics/ldl/)
- [Homocysteine](https://durgical.com/en/biochemistry/molecules/homocysteine/)
- [Lipoprotein metabolism](https://durgical.com/en/biochemistry/topics/lipoprotein-metabolism/)
- [Apolipoprotein E (ApoE)](https://durgical.com/en/biochemistry/enzymes/apolipoprotein-e/)

## Connections

## Related 5

- [How an atheroma forms: the response-to-injury model step by step](https://durgical.com/en/general-pathology/how-an-atheroma-forms-the-response-to-injury-model-step-by-step/)
- [Atherosclerotic plaque: stable vs vulnerable](https://durgical.com/en/general-pathology/atherosclerotic-plaque-stable-vs-vulnerable/)
- [Tobacco: how smoking injures tissue](https://durgical.com/en/general-pathology/tobacco-how-smoking-injures-tissue/)
- [Obesity: leptin, adipokines and its consequences](https://durgical.com/en/general-pathology/obesity-leptin-adipokines-and-its-consequences/)
- [Systemic effects of inflammation: fever, acute-phase proteins, leukocytosis, sepsis](https://durgical.com/en/general-pathology/systemic-effects-of-inflammation-fever-acute-phase-proteins-leukocytosis-sepsis/)

## Related conditions 6

- [Atherosclerosis and dyslipidaemia](https://durgical.com/en/conditions/atherosclerosis-and-dyslipidaemia/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)
- [Myocardial Infarction (Heart Attack)](https://durgical.com/en/conditions/myocardial-infarction/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Atherosclerosis | Arteriosclerosis | MedlinePlus](https://medlineplus.gov/atherosclerosis.html) (MedlinePlus, US National Library of Medicine, 2025); [Familial hypercholesterolemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia/) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/atherosclerosis-risk-factors/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/atherosclerosis-risk-factors/