Atherosclerosis Associated Risk Factors

Atherosclerosis: a slowly progressive disease of arteries, marked by elevated fibro-fatty intimal plaques, formed by lipid deposition, SMC proliferation and synthesis of ECM in the intima.

Constitutional risk factors:

• Age: risk Increases with advancing age

• Sex: females seem to be protected before menopause

• Familial disposition

Controllable major risk factors:

Hyperlipidemia: lipids in atheromatous plaques consist mainly of cholesterol; Raised cholesterol (by drugs) -> atheroma and the risks of complications.

Risk of atherosclerosis is correlated with the level of serum low-density lipoprotein (LDL), formed from the catabolism of very-low-density lipoprotein (VLDL). LDL carries 70% of total serum cholesterol thus high levels of which are important risk factors i.e.:

• Total cholesterol: >6.2mmol/L (normal <5.2)>

• LDL cholesterol: > 4.2mmol/L (normal <3.4)>

Elevated LDL levels  accelerated atherosclerosis.

Hyperlipidemia and hypercholesterolemia may be caused by:

• Familial abnormalities (of LDL receptor gene or in various apolipoprotein genes)

• Diet high in cholesterol and saturated fat

• Diabetes mellitus (a major risk factor in itself)

• Hypothyroidism

Others including uraemia, nephrotic syndrome and obstructive liver disease

On the contrary, risk of atherosclerosis is inversely related to the level of high-density lipoprotein (HDL), involved in reverse transport of cholesterol from cells; potentially helps clear cholesterol from vessel wall lesions and thus has a protective effect. HDL levels may be:

• Increased by exercise and moderate alcohol intake

• Decreased by smoking and obesity

Hypertension:

• Major risk factor especially in >40 year olds

• BP>160/95 results in 5 incidence of IHD compared to BP<140/90>

Diabetes mellitus:  risk of developing MI 2 (hypercholesterolemia)

Smoking:

• >1 packs a day for some years will  death rate from IHD by ^2

• Stop smoking will lower risk

Note: multiple risk factors have additive effects:

• 2 major risk factors increse risk of IHD by ^4

• 3 major risk factors Increase risk of IHD by ^7

Other minor risk factors:

• Obesity (>30% overweight)

• Sedentary lifestyle with low physical activity

• Stress or type A personality behaviour (aggressive competitive)

• ^ homocystine levels ^ ^ lipoprotein

• High CHO diet  hardened unsaturated fat intake

• Post menopausal oestrogen deficiency

Note: it follows that the risks can be reduced by measures that manage or prevent the ‘controllable’ risk factors.

Category: Pathology Notes