*5.7.3 Serum folate levels*

*Lifestyle and Epidemiology - The Double Burden of Poverty and Cardiovascular Diseases...*

mia in all age groups in urban, peri-urban and rural areas in SA is concerning.

**5.6 Haemostasis**

**5.7 Homocysteine metabolism**

homocysteine increase superoxide (O2

*5.7.2 Serum vitamin B6 levels*

*5.7.1 Homocysteine*

(EC), [24] 6.5% peri-urban children (FS), and 6.9% peri-urban children (Gauteng) had high serum glucose levels. An increased prevalence of diabetes was reported for developing countries, [85] and it can be concluded that the prevalence of hyperglycae-

The development of coronary artery disease and myocardial infarction has both atheromatous and thrombotic components. Haemostasis is a finely balanced system of clot formation and fibrinolysis. [86–88] Fibrinogen is recognised as an independent risk marker of CVD. Fibrinogen, because of its mass, also has a direct effect on the blood viscosity and a physical functional effect on platelet aggregation. [65, 89] Studies have indicated an increased level of plasma fibrinogen in black South Africans. [12, 57, 90] An increase of one gram per litre in plasma fibrinogen doubles the risk of CVD. [89] The fibrinogen levels were measured in two of the communities. High fibrinogen levels were observed in 68.0% of the elderly [57] (**Table 2**) and 14.8% of the rural children (**Table 3**), indicating an increased risk for CVD.

Several mechanisms have been proposed to clarify the link between homocysteine and pro-thrombotic state. The oxidative damage to the endothelium, combined with inhibition of the vasculo-protective function of nitric oxide, enhances thrombogenecity. [91] Homocysteine is metabolised by (a) the trans-sulphuration pathway which results in the production of cystathionine - a process that requires vitamin B6 and the main route of metabolism is via a methionine-conserving pathway - a process that requires methyltetrahydrofolate (from folic acid) and vitamin B12 as co-factor or alternatively (b) by the remethylation pathway taking place in the kidney and liver (where betaine is utilised instead of folate). [92–95] An association between elevated plasma homocysteine and the development of atherosclerosis has been confirmed. [96] Studies in animal models have shown that elevated homocysteine promoted atherosclerosis by increased oxidative stress impaired endothelial function and increased thrombogenecity. [92, 93, 95–99] Epidemiological retrospective and prospective clinical studies established homocysteine as a potent independent risk factor for atherothrombotic vascular disease. [91, 92, 100] Additionally,

stress, causing an inflammatory state and increased atherosclerosis and ischemia reperfusion. Oxidative stress in return inhibits the cobalamine metabolism and enhances the cycle. [101, 102] The frequency of hyperhomocysteienaemia as an independent risk factor for atherothrombotic vascular disease [91, 92, 100] was found in 66.4% and 1.6% of the urban elderly [57] and rural children respectively. Thus, although homocysteine measurement did not form part of the objectives in all our communities, prevalence of hyperhomocysteienaemia in the urban elderly (Gauteng) (**Table 2**) and the rural children (EC) (**Table 3**) is an additional confirmation of an increased risk for CVD in the low income South African population.

Vitamin B6 acts as coenzyme in the irreversible trans-sulfuration of homocysteine to cysteine. Higher vitamin B6 level are associated with lower homocysteine levels. Fat metabolism requires carnitine, obtained either directly [103] through diet or via

—) levels resulting in increased oxidative

**52**

Low serum folate levels is a cardiovascular risk marker independently from homocysteine level. [109] Folate, as a donor of one-carbon units, is essential for methylation and affects numerous metabolisms involved in CVD [110] and accurate replication of deoxyribonucleic acid (DNA) and its repair. If DNA repair capacity of the cell is exceeded by the rate of damage to the genome, serious defects in cellular and tissue physiology occur, resulting in degenerative diseases including CVD. [111] The four mechanisms by which folate is involved in reducing atherosclerosis are: (1) Optimising methylation cycle and thereby directly reducing the homocysteine levels; (2) Acting directly as an antioxidant; (3) Interacting with enzyme endothelial nitric oxide synthase; (4) Affecting cofactor bioavailability of nitric oxide. Apart from being an independent cardiovascular risk marker, decreased serum folate levels also Indicate a decreased cell regeneration. [112] The serum folate levels were only available for two of the communities and 4.8% and 7.6% had low folate levels in the elderly [57] (**Table 2**) and rural children (EC) (**Table 3**) respectively. Study communities included in this study are therefore at risk for CVD and the general effect of ineffective cell recovery.
