The Treatment of Coronary Heart Disease: An Update: Part 1: An Overview of the Risk Factors for Cardiovascular Disease


Curr Med Res Opin. 2001;17(1) 

In This Article

New Cardiovascular Risk Factors

In addition to established risk factors, several other variables have been identified as predictors of vascular disease. Table 2 shows some of the most important new cardiovascular risk factors.

LVH is defined as a left ventricular mass exceeding 131 g/m2 of body surface area in men and 100 g/m2 in women and is the response of the heart to chronic pressure or volume overload[56]. Its incidence increases with age, BP and obesity[55]. LVH is independently associated with increased incidence of cardiovascular disease, cardiovascular and all-cause mortality, and stroke[57,58]. Effective BP control in hypertensive patients, along with non-pharmacological interventions such as weight reduction, sodium restriction and aerobic physical exercise, can reduce left ventricular mass[59,60,61]. There are no conclusive data that the reduction of left ventricular mass can improve cardiovascular outcome independently of the decrease in BP. Moreover, there are no standard universally accepted criteria for LVH, limiting the application of this risk factor in routine clinical practice[62]. However, LVH is associated with an increased risk of cardiac events within single studies.

A number of epidemiological and observational studies have suggested that increased fasting total homocysteine levels (> 15 mmol/l) are independently associated with CVD, myocardial infarction, peripheral vascular disease,cerebrovascular disease, stroke, cardiac allograft vasculopathy and CVD death[63,64,65]. However, the prospective studies have yielded controversial results concerning the potential importance of the increased homocysteine levels[64,66,67,68,69].

Genetic and nutritional factors, such as deficiencies in folate, vitamin B12 and vitamin B6, are associated with increased serum levels of homocysteine, while in patients with hyperhomocysteinaemia, supplementation with these vitamins can decrease homocysteine levels[65,70,71,72,73]. Large randomised clinical trials are underway to examine the potential benefits of decreasing homocysteine levels.

Controversy exists with regard to the role of elevated Lp(a) levels as a risk factor for vascular disease. Some prospective and retrospective studies have suggested an independent association between the increased Lp(a) levels (> 30 mg/dl) and the presence of CVD,myocardial infarction, cerebrovascular disease,restenosis after balloon angioplasty, or saphenous vein bypass graft disease, and cardiac allograft vasculopathy[74,75,76,77,78,79]. It also seems that increased Lp(a)levels can enhance the deleterious effects of hypercholesterolaemia[80]. However, other studies failed to show any association between Lp(a) and vascular disease[80,81,82,83,84]. A number of factors could explain the conflicting results, including problems relating to the standardisation of the assays used and to sample handling[85,86,87]. Furthermore, there are no data showing that the decrease in Lp(a) levels is associated with a decrease in the incidence of cardiovascular or cerebrovascular disease[88,89]. The value of the routine screening for, and/or treating Lp(a) excess, is therefore still debatable. However,Lp(a) levels should probably be taken into account inpatients with CVD without established risk factors.Finally, in hypercholesterolaemic patients with increased Lp(a) levels, the decrease in LDL cholesterol levels is followed by neutralisation of the atherogenic potential of Lp(a)[90].

The exact role of increased triglyceride (TG) levels as a risk factor for atherosclerosis is not clear. A growing body of evidence, including a meta-analysis of 17 population-based prospective studies, as well as the results of the Copenhagen Male Study, suggest that hypertriglyceridaemia is an independent risk factor for CAD[91,92]. However, in multivariate analysis after adjustment for other risk factors, especially HDL cholesterol, the predictive power of the increased TGs is substantially reduced[93,94].Furthermore, there is a significant variation of fasting TGs[95]. Of particular importance is the relation of increased TGs with low HDL-C levels, high levels of small-dense LDL particles, and a procoagulant state[96,97]. Interestingly, indirect data from prospective clinical trials have pointed out that the reduction of TGs results in a significant decrease in CVD events[98,99,100,101,102]. It may be reasonable to attempt reduction in serum TGs in high-risk patients as well as in those with established vascular disease. Nonpharmacological measures are the cornerstone for the treatment of hypertriglyceridaemia, while in some patients, drugs (mainly fibrates) are necessary to restore normotriglyceridaemia[103].

A number of studies have clearly shown the association of increased plasma fibrinogen levels with cardiovascular disease[104,105]. Interestingly, preliminary results from the Bezafibrate Infarction Prevention(BIP) study have pointed out that the reduction of the increased fibrinogen levels in CAD patients could decrease the incidence of cardiac death and ischaemic stroke[106]. The substantial variability of plasma fibrinogen levels owing to a number of factors including the assay used, socioeconomic and metabolic factors, etc limit the wide application of this coagulation factor as a risk factor in every-day clinical practice[107,108,109,110]. It should be mentioned that smoking cessation, weight loss, regular exercise,moderate alcohol consumption and fibrates can significantly reduce plasma fibrinogen levels[105,111,112,113,114].

Several other factors participating in blood coagulation have been associated with CVD risk,including factor VII levels, plasminogen activator inhibition (PAI-1) and increased platelet aggregation[115,116,117]. Compelling evidence from randomised controlled trials now exists on the beneficial effect of antiplatelet agents (mainly aspirin) in the prevention of cardiovascular events in patients with established vascular disease[118]. However, there is no unequivocal evidence on the beneficial effect of aspirin in the primary prevention of CVD taking into account the long-term risks of therapy. It should be mentioned that in well-controlled treated hypertensive patients, as well as in men at particularly high risk, aspirin results in a significant decrease in cardiovascular events[118,119].

In one extensive trial, the long-term administration of clopidrogel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke,myocardial infarction or vascular death[120].

The oxidative modification of LDL plays a central role in the atherosclerosis process[121]. However, the role of antioxidant therapy for the prevention of vascular disease is not well established. In fact, while epidemiological and observational studies have shown that high intakes of vitamins E, C and A may provide protection against cardiovascular disease, the results of placebo-controlled primary prevention studies failed to show any benefit from the use of antioxidant vitamins[122,123,124]. Nevertheless, some secondary prevention studies have suggested potential beneficial effects of antioxidants[123,125].

Ongoing prospective primary and secondary clinical trials will delineate the role of antioxidants in the prevention of CAD. It is worth mentioning that dietary modification, such as mono-unsaturated fatty acids (as well as flavonoids) present in red wine,vegetables, fruits, tea, etc could significantly decrease the oxidative stress[126].

Recent data suggest the potential links between infectious agents and cardiovascular diseases.Numerous infectious agents have been considered as possible causes of vascular injury and inflammation for the development of vascular disease [cytomegalo virus,Chlamydia pneumoniae, Helicobacter pylori and herpes simplex virus (HSV)][127,128,129,130]. However, there area number of questions concerning the extent to which these micro-organisms play a role in the pathogenesis of atherosclerosis.

It has recently been stated that atherosclerosis is clearly an inflammatory disease and does not result simply from the accumulation of lipids[131]. Evidence linking inflammation to atherosclerosis stems from studies focusing on acute and chronic phases of CAD. Thus, markers of inflammation, such as Creactive protein, have recently been described as a potential predictor for future cardiovascular and cerebrovascular events[132,133,134]. Furthermore, elevated acute-phase reactants and cytokine production with a focal predominance of inflammatory cells have been found in patients with unstable coronary syndromes[135]. The circulating levels of these inflammatory markers are altered by treatment with lipid lowering drugs, such as pravastatin[136,137,138,139].


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