The Residual Risk Odyssey

Q: What are the key findings of this study?

In young, healthy adults, elevated Lipoprotein(a) in the highest quintile was associated with a higher incidence of any coronary heart disease (1.82 per 1,000 person-years) compared to the lowest quintile (1.03 per 1,000 person-years).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Atherosclerotic cardiovascular disease (ASCVD) (n=3920). Intervention: Elevated Lipoprotein(a) [Lp(a)] vs. Low Lipoprotein(a) [Lp(a)] (lowest quintile). Primary outcome: Incident any CHD.

Robert S. Rosenson; Sascha N. Goonewardena

doi:10.1016/j.jacc.2021.04.103

July 26, 2021Journal of the American College of CardiologyOpen Access

The Residual Risk Odyssey

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Key result

Top-quintile Lp(a) is linked to ~77% higher incident CHD in young, healthy adults.

n=3,920

Key Points

Investigate how circulating lipoprotein(a) levels and associated proteomic profiles relate to subclinical atherosclerosis, systemic inflammation, and long-term coronary heart disease risk.
Analyzed 3,920 CARDIA participants without baseline coronary heart disease followed for a median of 27.1 years, including a subcohort of 2,303 individuals with proteomic profiling.
Derived a 62-protein score using LASSO regression in CARDIA and externally validated the signature among 37,996 individuals in the UK Biobank over a median follow-up of 13.6 years.
Incidence of any and hard coronary heart disease was 1.82 and 1.43 per 1,000 person-years in the highest lipoprotein(a) quintile versus 1.03 and 0.93 per 1,000 person-years in the lowest quintile.
In joint adjusted models, the proteomic score remained independently associated with Year 25 incident coronary artery calcification (standardized β = 0.40, P < 0.0001) and hs-CRP (standardized β = 0.11, P = 0.00015).
In the UK Biobank validation cohort, the recalibrated proteomic score significantly predicted baseline CRP (fully adjusted P = 1.42 × 10–54), incident any coronary heart disease (fully adjusted P = 0.001), and all-cause mortality (fully adjusted P < 0.01).

Study Design

Type

Cohort (n=3,920)

Multicenter

Yes

PICO

P

Population

3,920 young, healthy adults aged 18-30 years at baseline, free of prior coronary heart disease, followed for a median of 27.1 years to assess the association between Lp(a) levels and incident cardiovascular events.

E

Exposure / Comparator

Elevated Lipoprotein(a) [Lp(a)] vs Low Lipoprotein(a) [Lp(a)] (lowest quintile)

O

Primary Outcome

Incident any CHD

Main Result

Absolute Event Rate: 1.82% vs 1.03%

Limitations

Observational design precludes strict determinations of causality.
Targeted Olink CVD panels limit the novelty of pathway-level findings since they are already enriched for cardiovascular proteins.
Lack of information on oxidized phospholipid content of Lp(a) which may link proteomic features to distinct Lp(a) properties.
Differences in baseline characteristics and proteomics platforms required external score recalibration rather than direct validation in the UK Biobank.
Did not correct for Lp(a)-C in standard determinants of LDL-C.
Potential residual confounding despite careful covariate adjustment.

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Implication

Elevated Lp(a) may flag higher long-term CHD risk in young adults; leaves open whether measurement or targeting improves outcomes.

Abstract

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Cite This Study

Rosenson et al. (2021) conducted a cohort in Atherosclerotic cardiovascular disease (ASCVD) (n=3,920). Elevated Lipoprotein(a) [Lp(a)] vs. Low Lipoprotein(a) [Lp(a)] (lowest quintile) was evaluated on Incident any CHD. In young, healthy adults, elevated Lipoprotein(a) in the highest quintile was associated with a higher incidence of any coronary heart disease (1.82 per 1,000 person-years) compared to the lowest quintile (1.03 per 1,000 person-years).

synapsesocial.com/papers/6acf1544e9cf455829e37422 https://doi.org/10.1016/j.jacc.2021.04.103

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The Residual Risk Odyssey

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

The Residual Risk Odyssey

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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