Atherosclerosis – risk factors and complications

ATHEROSCLEROSIS – RISK FACTORS AND COMPLICATIONS

ATHEROSCLEROSIS

• Atherosclerosis means thickening and hardening of medium sized vessel due to involvement of intima.

• Atherosclerosis term is derived from Greek word “Athero” means “gruel or porridge” and “sclerosis” means “hardening”.

• Incidence – high in developed countries and low in Africa, Asia, Central and south America

• Sites – large and medium sized arteries are involved. Most commonly involved are aorta, coronary arteries, carotid artery and iliac arteries

RISK FACTORS

• Risk factors for atherosclerosis can divided into

  • Non – Modifiable risk factors

  • Modifiable risk factors

  • Other associated risk factors

NON MODIFIABLE RISK FACTORS

• • Increasing age – progresses with age and manifests in middle age (40-60years)

  • Gender – 

    • Males are at increased risk.

    • Premenopausal women are relatively protected except if they are associated with hypertension, hyperlipidemia and diabetes

    • After menopause females also have increased risk.

  • Genetic factors- family history and familial clustering of other established risk like hypertension or diabetes or hyperlipidemia

MODIFIABLE RISK FACTORS

• • Hyperlipidemia

  • Hypertension

  • Diabetes mellitus

  • Cigarette smoking

• Hyperlipidemia

  • Hypercholesterolemia is major risk factor

  • LDL transports cholesterol to peripheral tissue whereas HDL transports cholesterol from the periphery to the liver for excretion in bile. Hence high levels of HDL correlates with reduced risk

  • Omega – 3 fatty acids are abundant in fish oils which are beneficial where as unsaturated fats (produced by hydrogenation of polyunsaturated oils) in baked foods adversely affect cholesterol profiles.

  • Exercise and moderate consumption of ethanol raises HDL where as obesity and smoking lowers it

  • Statins – drugs which lowers circulating cholesterol by inhibiting hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase, the rate limiting step in hepatic synthesis of cholesterol

• Hypertension

  • It is a major risk factor, probably because it causes vessel wall damage due to increased pressure. Increases the risk of IHD by 60%

• Cigarette smoking 

  • One or more packs of cigarette /day increases the risk of ischemic heart disease to 70% to 80%

• Diabetes mellitus – induces hypercholesterolemia and marked increase in the risk of atherosclerosis

ADDITIONAL RISK FACTORS

• Inflammation –

  • C – reactive protein (CRP) is used as marker of inflammation and also marker of risk for MI, stroke and peripheral arterial disease

  • CRP is synthesized in liver and its expression is increased by inflammatory mediators IL-6.

  • CRP binds to bacteria and also activates classical complement cascade

• Hyperhomocysteinemia

• Metabolic syndrome –

  • Characterized by insulin resistance, hypertension, dyslipidemia (increased LDL and decreased HDL), hypercoagulability and a proinflammatory state.

  • Hypercoagulability and proinflammatory state contributes to endothelial dysfunction or thrombus.

• Abnormal apoproteins

• Lipoprotein a [LP(a)] 

  • LP(a) is an altered form of LDL that contains the apoprotein B-100 portion of LDL linked to apolipoprotein A.

  • LP(a) levels are associated with coronary and cerebrovascular disease risk, independent of cholesterol or LDL levels.

• Factors affecting hemostasis – like fibrinolytic agents (Plasminogen activator inhibitor 1), platelet derived factors (thrombin) act as indicators for the risk of vascular pathology

• Lack of exercise

• Stressful life style (type A personality)

• Obesity

• Use of exogenous hormones

COMPLICATIONS OF ATHEROSCLEROTIC PLAQUE

• Atherosclerotic stenosis

• Acute plaque changes – Rupture, ulceration or erosion – of the surface leads to exposure of highly thrombogenic substances which causes thrombosis producing obstruction of the lumen

• Hemorrhage into plaque – occurs due to rupture of the overlying fibrous plaque or blood vessels of neovascularization leading to intraplaque hemorhage producing expansion of the plaque due to hematoma

• Atheroembolism – Plaque rupture release contents of atherosclerotic debris into the blood stream producing microemboli

• Aneurysm formation – atherosclerosis induced pressure or ischemic atrophy of the underlying media, with loss of elastic tissue causes weakness and potential rupture

• Calcification – dystrophic calcification occurs in atherosclerotic plaques

References

1. Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.