Identifying an optimal cutpoint for the diagnosis of hypertriglyceridemia in the nonfasting state
Open accessAbstract
BACKGROUND: Nonfasting triglycerides are similar or superior to fasting triglycerides at predicting cardiovascular events. However, diagnostic cutpoints are based on fasting triglycerides. We examined the optimal cutpoint for increased nonfasting triglycerides. METHODS: We obtained baseline nonfasting (<8 h since last meal) samples from 6391 participants in the Women's Health Study who were followed prospectively for ≤17 years. The optimal diagnostic threshold for nonfasting triglycerides, determined by logistic regression models by use of c-statistics and the Youden index (sum of sensitivity and specificity minus 1), was used to calculate hazard ratios (HRs) for incident cardiovascular events. Performance was compared to thresholds recommended by the American Heart Association (AHA) and European guidelines. RESULTS: The optimal threshold was 175 mg/dL (1.98 mmol/L), with a c-statistic of 0.656, statistically better than the AHA cutpoint of 200 mg/dL (c-statistic 0.628). For nonfasting triglycerides above and below 175 mg/dL, after adjusting for age, hypertension, smoking, hormone use, and menopausal status, the HR for cardiovascular events was 1.88 (95% CI 1.52–2.33, P < 0.001), and for triglycerides measured at 0–4 and 4–8 h since the last meal, 2.05 (1.54– 2.74) and 1.68 (1.21–2.32), respectively. We validated performance of this optimal cutpoint by use of 10-fold cross-validation and bootstrapping of multivariable models that included standard risk factors plus total and HDL cholesterol, diabetes, body mass index, and C-reactive protein. CONCLUSIONS: In this study of middle-aged and older apparently healthy women, we identified a diagnostic threshold for nonfasting hypertriglyceridemia of 175 mg/dL (1.98 mmol/L), with the potential to more accurately identify cases than the currently recommended AHA cutpoint.
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For nonfasting samples, the threshold for abnormal TG concentrations is ≥2 mmol/L according to the Women's Health Study, which found that this threshold was optimal for ASCVD prediction.
“For nonfasting samples, laboratories should flag abnormal TG concentrations as ≥2 mmol/L according to the Women's Health Study, which found that this threshold was optimal for ASCVD prediction [91].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [91]
The Results and Discussion identify 175 mg/dL (1.98 mmol/L, approximately 2 mmol/L) as the optimal nonfasting triglyceride cutpoint for predicting incident CVD in the Women’s Health Study. The paper proposes a diagnostic cutpoint, but does not specifically direct laboratories to flag results at that level; its measured outcome is a composite of CVD events rather than an outcome expressly defined as ASCVD. (LLM, conf=0.82)
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- Authors
- White, K. T., Moorthy, M. V., Akinkuolie, A. O., Demler, O., Ridker, P. M., Cook, N. R., & Mora, S.
- Affiliations
- Division of Preventive Medicine
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Mora, Samia
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-01
- Volume
- 61
- Issue
- 9
- Pages
- 1156-1163
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC4554926
- OpenAlex
- W2109221833
- Cited by
- 74
- References
- 45
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 18 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 8 · 2015: 1
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Women's Health Study (HL117861, HL43851, HL 080467, CA 47988)
- National Heart, Lung, and Blood Institute (T32 HL007575)
- National Cancer Institute
- Novartis
- AstraZeneca
- Aegerion
- ISIS
- Boehringer Ingelheim
- Pfizer
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- hypertriglyceridemia, cardiovascular risk, Women's Health Study, middle-aged and older women, cardiovascular events
- MeSH terms
- Cardiovascular Diseases, Fasting, Female, Humans, Middle Aged, ROC Curve, Triglycerides, Hypertriglyceridemia, Postprandial Period
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