| Li et al. (2025) meta-analysis | ePWV associated with increased cardiovascular events and mortality; no established cutoff; clinical utility not assessed. |
| Sequí-Domínguez et al. (2020) meta-analysis | cfPWV predictive for cardiovascular and all-cause mortality (pooled DORs/AUC reported); incremental value and clinical utility not reported. |
| Multiple systematic reviews/meta-analyses (2017-2025) on CIMT | CIMT associated with future CVD and carotid plaque but provides modest incremental reclassification beyond traditional risk factors; clinical utility unclear. |
| Emerging Risk Factors Collaboration (Di Angelantonio et al., 2012) | Adding emerging lipid markers (apoB, Lp(a), Lp-PLA2) to total cholesterol and HDL-C did not significantly improve CVD risk prediction. |
| Lp(a) and stroke recurrence (Palaiodimou et al. 2025) | Elevated Lp(a) associated with stroke recurrence (OR 1.69, 95% CI 1.09–2.63) and poor functional outcome (OR 2.09, 95% CI 1.40–3.11). |
| Lp(a) and long-term MACE (Berman et al. 2024) | In cohort of 16,419, 71st–90th percentile Lp(a) adjusted HR 1.21 and 91st–100th percentile HR 1.26 for MACEs; measurement clinical utility not established. |
| Women's Health Study (Ridker et al. 2024) | Top vs bottom quintile HR for first MACE: Lp(a) 1.33 (95% CI, 1.21–1.47); authors note Lp(a) is genetically determined and measurement recommended once. |
| Lp-PLA2 meta-analyses (Hu et al. 2019; Tian et al. 2017; Li 2017a) | Elevated Lp-PLA2 associated with small increased relative risks for stroke and ischemic stroke (RRs/HRs vary by mass vs activity); overall clinical utility not established. |
| Multiprotein panels (systematic reviews, Neumann 2024, Hayes 2023) | Biomarkers/panels show associations with events and some high AUCs in select cohorts, but generally add minimal improvement to established risk models and clinical utility is unproven. |
| Endothelial function (PAT/flow-mediated dilation) evidence (Cooper 2021; Schnabel 2021; Venuraju 2019; Hamburg 2008) | Studies report conflicting or null associations with composite CVD events; PAT measures not predictive for composite CVD in large cohorts though lower PAT ratio linked to higher incident stroke in some analyses; overall insufficient evidence of clinical utility for risk prediction. |
| PAT association with CVD/stroke (Cooper et al.; sensitivity analyses) | In Framingham analyses PAT ratio not associated with composite CVD events but higher PAT ratio associated with lower incident stroke risk (sensitivity analyses); results inconsistent and clinical utility not established. |
| Schnabel et al. (2021) | Peripheral vascular function measures (flow-mediated dilation, PAT) did not show clinically relevant associations with incident CVD or mortality in a large community cohort; routine measurement not supported. |
| Endo PAT 2000 FDA clearance (K032519) | Cleared as a diagnostic aid for detection of coronary artery endothelial dysfunction in patients with ischemic signs/symptoms undergoing angiography evaluation; not intended for general population screening. |
| Guideline statements (ESC/EAS 2025; NLA 2024; ACC/AHA; AACE; ASCP; USPSTF) | Guidelines recommend measuring Lp(a) at least once (ESC/EAS, NLA); generally discourage routine use of CIMT, arterial stiffness, PAT, and expanded lipid panels for population screening; apoB considered in selected contexts. |