Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis

https://doi.org/10.1016/j.numecd.2020.07.002Get rights and content

Highlights

  • Remnant cholesterol is nowadays of great scientific interest.

  • Remnant cholesterol is associated with cardiovascular events and all-cause mortality.

  • Competitive risks analysis allows probing the complex relationship between causes of death.

  • Remnant cholesterol is a strong risk factor for cause-specific cardiovascular deaths.

Abstract

Background and aims

Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs).

Methods and results

Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L).

Conclusions

RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

Section snippets

Methods

Details about study populations have been published elsewhere [[25], [26], [27]]. Briefly, two different prospective cohort studies conducted by the Laboratory of Epidemiology and Biostatistics of the National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital (Castellana Grotte, Bari, Italy) were included. The MICOL Study [28] is a random sample study drawn from the electoral list of Castellana Grotte (≥30 years old) in 1985 and followed up in 1992, 2005–2006 and 2013–2016.

Baseline and follow-up characteristics

The study population included 5729 subjects from the MICOL II/Panel Study (3428) plus NUTRIHEP (2301). This study-base generated 86,049.99 person-years of observation. Median follow-up was 11.80 (IQR 10.75–28.58) years.

At the end of follow-up, 4868 subjects (84.9%) were alive/censored, whereas 861 (15.1%) had died. Causes of death were: 234 CVDs (27.2%), 245 CDs (28.5%) and 271 OCDs (31.5%). It was not possible to trace the cause of death (death certificate not found) for 111 subjects (12.8%).

Discussion

This competitive risk analysis investigated and quantified the effect of RC on cause-specific mortality. RC is a strong risk factor for CVDs. The estimates have been adjusted for several confounding factors to obtain more valid and precise measures. The novel aspect of this study is the competing risks survival analysis performed to estimate the risk and rate of RC on CVDs, CDs, and OCDs and the setting of study (general population).

Scientific evidence about the association between RC and

Funding

This work was supported by: MICOL II: This research was supported by a grant from the Ministry of Health, Italy (Progetto Finalizzato Ministero della Sanita Numero 11 Gazzetta Ufficiale Nr. 263 (Serie Generale), de1 7-X1-92). MICOL III: This research was supported by a grant from the Ministry of Health, Italy (Progetto Finalizzato del Ministero della Salute, ICS 160.2/RF 2003), 2004/2006). MICOL IV: This research was supported by a grant from the Ministry of Health, Italy (Ricerca Corrente DDG

Declaration of Competing Interest

None declared.

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