Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease<subtitle>Large-Scale Prospective Data</subtitle>

Abstract

Background: Large-scale prospective data are needed to determine whether associations between lipoprotein(a) (Lp[a]) and coronary heart disease (CHD) risk are independent of established risk factors, to characterize the shape of this relationship, and to quantify associations in relevant subgroups. Methods: Levels of Lp(a) were measured in samples obtained at baseline from 2047 patients who had first-ever nonfatal myocardial infarction or who died of CHD during the study and from 3921 control participants in the Reykjavik Study (n=18 569), as well as in paired samples obtained 12 years apart from 372 participants to quantify within-person fluctuations. Results: Baseline Lp(a) levels had little or no correlation with known cardiovascular risk factors, such as age, sex, total cholesterol level, and blood pressure. The Lp(a) values were highly consistent from decade to decade, with a regression dilution ratio (calculated on the log scale) of 0.92 (95% confidence interval, 0.85-0.99). The odds ratio for CHD, unaltered after adjustment for several established risk factors (age, sex, smoking status, blood pressure, total cholesterol, triglycerides level, diabetes mellitus, and body mass index), was 1.60 (95% confidence interval, 1.38-1.85) in a comparison of extreme thirds of baseline Lp(a) levels. Odds ratios were progressively higher with increasing Lp(a) levels and did not vary materially by several individual-or study-level characteristics. Conclusions: There are independent, continuous associations between Lp(a) levels and risk of future CHD in a broad range of individuals. Levels of Lp(a) are highly stable within individuals across many years and are only weakly correlated with known risk factors. Further assessment of their possible role in CHD prevention is warranted.

The relationship between lipoprotein(a) and coronary artery disease, as well as its variable nature following myocardial infarction

“…Epidemiological studies show that Lp(a) is an independent risk factor for the development of premature coronary artery disease (CAD) and cerebrovascular disease, and that, at high levels, it is correlated with atherosclerosis [2][3][4][5][6].…”

Transesophageal Echocardiographic Evaluation of Atherosclerosis

“…One decade after our report detailed above, Peltier et al supported our data in a study using a similar TEE method in a larger population. 25) However, because lipoprotein (a)-lowering medications have not been developed, and because the correlation between coronary atherosclerosis and lipoprotein (a) is controversial, [26][27][28] medical intervention to decrease lipoprotein (a) has not progressed in the meantime. The other serum marker of aortic atherosclerosis that was found using this method was fibrinogen, 29) but it was not applied to therapeutic strategies for aortic atherosclerosis.…”

Serum Lipoprotein (a) as an independent marker of cardiovascular risk in patients with Essential Hypertension

“…The role of Lp(a) [lipoprotein(a)] as an independent biomarker of vascular risk has been investigated for more than 20 years, but recently the European Atherosclerosis Society (EAS) has issued a new consensus statement endorsing routine measurement of Lp(a) among patients with moderate to high risk of cardiovascular disease 2 . Many prospective epidemiological studies have reported positive associations of baseline Lp(a) concentration with coronary heart disease (CHD) risk 3 , but very limited case-control studies studied the association between elevated Lipoprotein (a) and essential hypertension that frequently occurs in conjunction with metabolic disturbances and in particular with atherogenic dyslipidemia 4 . The Lp (a) was described for the first time in 1963 by Berg.…”

“…5 It consists of a set of lipoproteins with different molecular weights (from 350 to 900 KD) 6 , in which particles of Low density lipoprotein (LDL) are bonded to apoprotein(a) (apo(a)), which has a Cringle structure with a high level of homology to plasminogen 5 . The physiological function of this lipoprotein is still unknown but the importance attributed to it has increased considerably in the light of the evidence that high plasma concentrations of Lp(a) are not only associated with an increased risk of vascular diseases such as CHD and the re-stenosis of coronary bypass but are also considered an independent risk factor for these pathologies 3 . Lipoprotein (a) [Lp (a)] is considered as a risk factor for vascular diseases, especially those associated with renal failure.…”