What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular disease risk (n=7586). Intervention: Lipoprotein(a) ≤10th percentile vs. Lipoprotein(a) >10th percentile. Primary outcome: Incident CVD events (non-fatal MI, non-fatal stroke, and cardiovascular death) (HR 0.67, 95% CI 0.47-0.95).

What does this research mean for the field?

Preferable levels of non-traditional risk markers, specifically lipoprotein(a) ≤5 mg/dL, a normal ECG, and carotid intima-media thickness ≤0.5 mm, effectively downgrade predicted cardiovascular risk beyond traditional risk factors, with low lipoprotein(a) associated with a 33% lower risk of incident CVD events. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 15, 2022Open Access

Negative Risk Markers for Cardiovascular Risk Evaluation in Chinese Adults

LBLizhan BieYancheng Third People's Hospital JNJingya NiuShanxi Agricultural University SWShujing WuZhejiang Chinese Medical University

Key Result

Lipoprotein(a) ≤5 mg/dL, normal ECG, and CIMT ≤0.5 mm downgraded predicted cardiovascular risk, with lipoprotein(a) ≤5 mg/dL associated with a 33% lower risk of incident CVD events (HR 0.67).

Study Design

Type

Cohort (n=7,586)

Multicenter

Structured PICO

Do negative risk markers (lipoprotein(a) ≤ 5 mg/dL, normal ECG, CIMT ≤ 0.5 mm) improve risk reclassification and downgrade predicted ASCVD risk in Chinese adults?

Population

7,586 Chinese adults aged ≥ 40 years without a history of CVD, mean age 57.9, 37.8% male, median 10-year ASCVD risk 6.7%.

Intervention

Evaluation of negative risk markers including lipoprotein(a) ≤ 10th percentile (5 mg/dL), normal ECG, and carotid intima-media thickness (CIMT) ≤ 25th percentile (0.5 mm) added to traditional CVD risk factors

Comparator

Traditional CVD risk factors alone

Outcome

Composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death at median 4.5 years follow-upcomposite

The presence of negative risk markers such as lipoprotein(a) ≤ 5 mg/dL, normal ECG, and CIMT ≤ 0.5 mm can effectively downgrade predicted 10-year ASCVD risk in Chinese adults, potentially reducing overtreatment in those classified as high-risk by traditional equations.

Main Result

Effect estimate: HR 0.67 (95% CI 0.47-0.95)

Absolute Event Rate: 3.8% vs 5.72%

Limitations

Limited number of CVD events due to a relatively short duration of follow-up
All tests and measurements were conducted only once
CIMT was measured only at the common carotid arteries
The Pooled Cohort Equations used to predict ASCVD risk were developed in western populations
Other potential negative risk markers such as CAC = 0 were not evaluated
Generalizability is limited to Chinese community residents aged ≥40 years

Abstract

Background: The atherosclerotic cardiovascular disease (ASCVD) risk predicted by traditional risk factors is used to guide preventive treatment. We aimed to investigate whether preferable levels of non-traditional emerging risk factors (i.e., negative risk markers) could downgrade the predicted ASCVD risk beyond traditional risk factors. Methods: A total of 7,568 Chinese adults aged ≥ 40 years were followed up during 2010-2015. Negative risk markers including non-traditional lipids, urinary albumin-to-creatinine ratio, electrocardiogram (ECG), and measurements of atherosclerosis were evaluated using diagnostic likelihood ratio (DLR) and continuous net reclassification index (NRI) for their ability to downshift predicted CVD risk in the overall study population and in participants with intermediate (traditional risk factor predicted ASCVD risk 7.5% to 19.9%) or high risk (≥20%). Results: During a median follow-up of 4.5 years, 416 participants developed CVD events including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Among negative risk markers examined, lipoprotein(a) ≤ 10th percentile (5 mg/dL), normal ECG, and carotid intima-media thickness (CIMT) ≤ 25th percentile (0.5 mm) provided moderate CVD risk reclassification and downward changes in pre- to post-test risk on top of the traditional CVD risk factors, especially in high-risk participants. The DLRs were 0.41, 0.75, and 0.41, and the NRIs were 18, 22, and 14% for lipoprotein(a), ECG, and CIMT, respectively in high-risk participants. Conclusions: Lipoprotein(a) ≤ 5 mg/dL, normal ECG, and CIMT ≤ 0.5 mm might be used as negative non-traditional risk markers to correctly downgrade predicted ASCVD risk in Chinese adults.

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