Neutrophil-based inflammatory indices and cardiovascular mortality in adults with hypertension: incremental prognostic value beyond the PREVENT equations and heterogeneity by race. A secondary analysis of NHANES 2005–2018 linked to the National Death Index
Year: 2026
Type: study-registration
Abstract: This preregistration describes a secondary analysis of the US National Health and Nutrition Examination Survey (NHANES, seven cycles from 2005–2006 to 2017–2018) linked to the National Death Index through 31 December 2019. Purpose. The systemic immune-inflammation index (SII; platelets × neutrophils / lymphocytes) and the neutrophil-to-lymphocyte ratio (NLR) are calculated from a routine full blood count. Previous NHANES studies reported that higher values are associated with cardiovascular death in adults with hypertension, but none tested whether these indices improve risk prediction beyond established risk equations, whether they perform equally in Black adults, who have lower neutrophil counts on average because of the Duffy-null variant, or whether the association persists when blood pressure is controlled. These questions matter most in low-resource settings, such as much of sub-Saharan Africa, where a blood count is often the only laboratory test available. Design. Prospective cohort analysis of about 10,500 adults aged 30–79 years with hypertension and no prior cardiovascular disease. The primary outcome is cardiovascular death; the secondary outcome is all-cause death. We will (1) estimate survey-weighted, design-based Cox models adjusted for the PREVENT predictors and socioeconomic factors; (2) assess incremental predictive value beyond the PREVENT predictors using optimism-corrected C-statistics, calibration, net reclassification and decision curve analysis; (3) compare distributions, associations and predictive value between non-Hispanic Black and non-Hispanic White adults; and (4) examine adults with treated, controlled blood pressure. Missing covariates will be multiply imputed. Pre-specified sensitivity analyses address reverse causation, competing risks, C-reactive protein, alternative hypertension definitions and unmeasured confounding. Expected outcomes. Estimates of the association and of the added prognostic value of SII and NLR, with evidence on whether thresholds derived in mixed populations are appropriate for people of African ancestry. The registered protocol, data dictionary and analysis code (with SHA-256 checksums) are archived with this registration. Results will be reported according to STROBE and TRIPOD+AI, and submitted to PLOS Medicine.
Source: Open Science Framework
Author: Raúl Fernandes Tchitali
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223442312