2.5 Primary and secondary prevention of atherosclerosis

Modifiable and non-modifiable risk factors for atherosclerosis

• Non-modifiable

  • Age: Men above the age of 45, Women above the age of 55 — risk increases with age

  • Gender: Males higher risk pre-menopause; female risk rises post-menopause

  • Genetics / Family history: First-degree relative with premature CVD (men less than 55, women less than 65).

  • Race / Ethnicity: Certain groups have higher baseline risk

• Modifiable (major)

  • Hyperlipidaemia: High LDL-C (bad cholesterol), low HDL-C (good cholesterol), high triglycerides (bad cholesterol)

  • Hypertension: BP more than 140/90 or on antihypertensive meds

  • Smoking: Strong dose-response effect

  • Diabetes mellitus: Both type 1 and 2; accelerates atherogenesis (The process of forming atherosclerotic plaques in the arterial wall)

• Additional risk factors (some modifiable)

  • Physical inactivity

  • Obesity / metabolic syndrome

  • Poor diet (high sat/trans fats, low fruit/veg/nuts/whole grains)

  • Chronic inflammation

  • Hyperhomocysteinaemia

  • Abnormal apolipoproteins (The protein components of lipoproteins that help stabilise their structure and act as ligands for receptors), elevated Lipoprotein(a) (an LDL particle with apolipoprotein(a) that raises atherosclerosis and clot risk)

  • Sleep apnoea (A sleep disorder where breathing repeatedly stops and starts, lowering oxygen levels and increasing cardiovascular risk.)

  • Chronic kidney disease

  • Air pollution, gut microbiome changes

Role of secondary prevention in atherosclerosis

• Goal: Prevent recurrence of ACS and other atherosclerotic events

• Rationale:

  • 34% of ACS cases are repeat events

  • Repeat MI mortality ~20% vs ~10% for first MI

• Evidence:

  • ↓ Cholesterol by 10% → ↓ Coronary Heart disease (CHD) by 20-30%

    • Lowering blood cholesterol, especially LDL-C, reduces the amount of lipid available to form plaques. Even a modest 10% drop leads to a large relative reduction in coronary heart disease events because LDL-C is a major driver of atherogenesis.

  • ↓ BP by 5-6mmHg → ↓ Stroke risk by 42%, ↓ Coronary Heart disease (CHD) by 16%

    • Lowering systolic blood pressure slightly reduces the strain on vessel walls, lowering the risk of plaque rupture and haemorrhage. Stroke risk drops more dramatically than CHD risk because high BP is a stronger direct cause of stroke (especially haemorrhagic and lacunar types).

  • Smoking cessation → ↓ Coronary Heart disease (CHD) risk by 50-70%

    • Stopping smoking rapidly improves vascular function, reduces inflammation, and improves lipid profiles. The large risk reduction happens because smoking damages endothelium, increases clotting tendency, and accelerates plaque growth — and removing that trigger has an immediate and long-term benefit.

Post-MI Standard secondary prevention (unless contraindicated)

1. Antiplatelet therapy: Aspirin + ticagrelor/prasugrel/clopidogrel (12 months or longer)

2. High-intensity statin: Atorvastatin 80 mg or rosuvastatin 40 mg

3. ACE inhibitor

4. β-blocker

5. Lifestyle measures: Smoking cessation, physical activity, healthy diet, weight management, depression management

6. Cardiac rehab

7. Education on warning signs

Role of Hyperlipidaemia and Hypercholesterolaemia in Atherosclerosis

• Pathophysiology:

  • ApoB-containing lipoproteins (VLDL, IDL, LDL, Lp(a), chylomicrons) penetrate endothelium → become modified → trigger inflammation → macrophage recruitment → foam cell formation → plaque growth.

  • LDL-C strongly correlates with future coronary events — no safe lower limit found

• Treatment Targets (Australia / ESC 2019):

  • Very high risk (post-ACS): LDL-C <1.8 mmol/L (often <1.4 mmol/L or even <1.0 mmol/L in recurrent events)

  • HDL-C ≥ 1.0 mmol/L; TG <2.0 mmol/L; Non-HDL-C <2.5 mmol/L

• Lipid-Lowering Therapy:

  • Statins (first-line): Inhibit HMG-CoA reductase (Enzyme in liver that makes cholesterol) → Cholesterol production in the liver is inhibited → LDL drop by ~50%

  • Ezetimibe: Blocks intestinal cholesterol absorption (extra 15–25% LDL-C reduction).

  • PCSK9 inhibitors (e.g., evolocumab, alirocumab): Increase LDL receptor recycling (↓ LDL-C by 60–75%).

• Lifestyle:

  • Replace saturated/trans fats with mono/polyunsaturated fats.

  • Increase fibre (5–10 g/day soluble fibre ↓ LDL-C by 5%).

  • Plant sterols/stanols 2 g/day ↓ LDL-C by up to 15%.

  • Mediterranean/DASH diets – synergistic benefit.