**Abstract**

In this chapter we will discuss more about the role of homocysteine in atherosclerosis and also association between serum homocysteine with extracranial carotid atherosclerosis. Carotid atherosclerosis comprises an increase in carotid intima-media (CIMT) thickening, plaque formation and carotid stenosis. Atherogenic property of homocysteine was discovered in 1969. Atherosclerosis is initiated by endothelial dysfunction. One of the causes of endothelial abnormality is homocysteine. The development of aggregates of homocysteinylated lipoproteins with microorganisms obstructs the vasa vasorum in vulnerable plaques. In one study, serum homocysteine in the highest quartile was independently associated with extracranial carotid artery stenosis ≥50%. In another study, raised serum homocysteine was also independently associated with severe extracranial carotid stenosis in both genders. In other studies, serum homocysteine was significantly associated with carotid artery stenosis in internal carotid arteries and external carotid arteries as well as the degree of stenosis. The hypertensive patients who had raised serum homocysteine were reported to have higher risk of developing asymptomatic extracranial carotid artery stenosis.

**Keywords:** homocysteine, carotid, extracranial, atherosclerosis, stenosis

#### **1. History**

Premature atherosclerosis was first reported by McCully in 1969 [1]. He described it on two infant patients with raised homocysteine with similar arterial changes [1]. These two patients had large- and medium-sized arterial narrowing [1]. The histology was focal fibrosis of intima and media layers, focal proliferation of perivascular connective tissue of small arteries, as well as prominent internal elastic membranes in medium- and small-sized arteries [1].

Since then, numerous studies on homocysteine have been conducted. The level of homocysteine-cysteine mixed disulphide after a methionine load was shown to be slightly higher in the patients with coronary artery disease (CAD) in 1976 [2]. In addition, the fasting level of serum homocysteine was 31% higher in the patients with all vascular diseases than in controls [3]. Raised serum homocysteine was

found to be an independent risk factor for vascular diseases with odds ratios (OR) of 1.5 to 1.8 for every increase of 5 μmol/L in serum homocysteine [4]. In a metaanalysis, raised serum homocysteine was an independent predictor of ischaemic stroke and CAD in the healthy population [5].
