Abstract
BackgroundExperimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer.MethodsThe subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a)≥80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined.ResultsCumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15–1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00–2.13).ConclusionsThis is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results.
Highlights
Large-scale prospective cohort studies and their meta-analyses, including our study, have shown that hyperlipoproteinemia(a) is a risk factor for coronary artery disease and stroke [1,2,3,4]
The Jichi Medical School (JMS) Cohort Study The JMS cohort study was comprised of 12 population-based cohorts from the Tohoku to Kyusyu regions in Japan; the study was started in 1992 to clarify the risk factors for cardiovascular and cerebrovascular diseases among the Japanese population
The present study showed that a low Lp(a) level was a risk factor for all-cause, cancer, and miscellaneous-cause deaths
Summary
Large-scale prospective cohort studies and their meta-analyses, including our study, have shown that hyperlipoproteinemia(a) is a risk factor for coronary artery disease and stroke [1,2,3,4]. The apo(a) gene (LPA) and the plasminogen gene share a number of characteristic repeated domains called Kringle. Angiostatin, a degraded product of plasminogen, exerts an anti-neoplastic effect by inhibiting angiogenesis [8]. A phase II study on angiostatin has been performed in patients with non-small cell lung cancer [9]. As LPA has Kringle structures, apo(a) may have an anti-neoplastic effect [10]. A recombinant protein (LK68) of LPA Kringle type IV and V experimentally suppressed tumor growth and capillary density within tumors in mice [11]. Gene therapy inducing an LK68 recombinant gene suppressed the tumor growth of. Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer
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