Lipoprotein(a) and the risk of recurrent coronary heart disease: the Dubbo Study

Abstract

Objective

Elevated Lipoprotein(a) [Lp(a)] has not been firmly established as a risk factor for recurrent coronary heart disease (CHD). The present analysis explored this relationship in senior citizens.

Methods

This was a longitudinal study in 607 subjects, all with prevalent CHD, mean age 71 years, followed for 16 years. Baseline examinations of lipids and other CHD risk factors were conducted in 1988–89 in Dubbo, Australia. The independent contribution of Lp(a) to a further CHD event was examined in proportional hazards regression models.

Results

There were 399 incident CHD cases. Median Lp(a) in CHD cases was 130 mg/L (Interquartile range 60–315) and in non-cases 105 mg/L (45–250) (p < .07, U-Test). 26% of CHD cases and 19% of non-cases had Lp(a) 300 + mg/L; 18% of CHD cases and 8% of non-cases had Lp(a) 500 + mg/L. Lp(a) in Quintile 5 of its distribution (355 + mg/L), using Lp(a) Quintile 1 (<50mg/L) as reference, significantly predicted recurrent CHD with Hazard Ratio 1.53 (95% CI 1.11–2.11, p = .01). Prediction was independent of other risk factors. Lp(a) 500 + mg/L versus lower, significantly predicted recurrent CHD with Hazard Ratio 1.59 (1.16–2.17, p < .01). Prediction was similarly significant for Lp(a) 300 + mg/L versus lower, with Hazard Ratio 1.37 (1.09–1.73, p < .01).

Conclusion

Elevated Lp(a) is an independent and significant predictor of recurrent CHD in senior citizens. Upper reference Lp(a) levels of 500 mg/L (≈125nmol/L) or 300 mg/L (≈75nmol/L) both appear to be appropriate. The clinical benefit of therapy to reduce elevated Lp(a) remains to be confirmed.

PLAIN LANGUAGE SUMMARY

Lipoprotein(a) [Lp(a)], a type of “bad cholesterol”, has been shown to be an important cause of coronary artery disease (CAD). In the long-term Dubbo Study of senior citizens in Australia, Professor Simons’ team have previously shown that citizens with Lp(a) readings greater than 276 mg/L had a 46% greater chance of a first CAD problem (e.g. a heart attack) compared with those having much lower readings. This new study asked whether Lp(a) might also increase the chance of a second or repeat episode of CAD in citizens who had already manifested CAD. In 607 senior citizens with previous CAD followed for 16 years, those with Lp(a) readings greater than 355 mg/L had a 53% greater chance of manifesting another CAD problem compared with those having much lower readings. The team concluded that Lp(a) remains an important cause of repeat CAD in senior citizens. The benefit of emerging treatments to lower Lp(a) remains to be confirmed in ongoing research.

Keywords:

• Recurrent coronary heart disease
• Lipoprotein(a)
• senior citizens
• cohort study

Transparency

Declaration of funding

Novartis Pharmaceuticals Australia Pty Ltd provided an educational grant in support of the present analysis, but made no input to its design or preparation of the manuscript.

Declaration financial/other relationships

LAS reports previous research funding and speaker fees from manufacturers of lipid-modifying drugs, funding unrelated to the Dubbo Study. JS reports no conflicting financial interests. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

This analysis was conceived and conducted by both authors who have been associated with the Dubbo Study since its inception. Both authors contributed to the manuscript and approved the final version.

Data availability statement

The Dubbo Study database can be made available to other academic investigators by agreement with the study authors.