Abstract Body (Do not enter title and authors here): Background and Aims High neutrophil counts, an easily accessible inflammation biomarker, has been linked to risk of cardiovascular disease (CVD), and mortality, but with mixed results. We aimed to summarize published associations between neutrophil counts with risk of CVD and all-cause and cause-specific mortality among generally healthy populations.
Methods We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until March 2024. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of neutrophil counts in relation to risk of CVD and all-cause and cause-specific mortality among general healthy populations. Linear and non-linear dose-response analyses were also performed.
Results Our systematic review and meta-analysis included 22 prospective cohort studies. During a median/mean follow-up period of 3.8 to 18.3 years, 73,934 CVD events and 80,317 deaths occurred among 1,962,191 participants. Higher neutrophil counts were associated with a higher risk of CVD incidence and all-cause mortality, CVD mortality, and non-CVD mortality. The pooled RRs (95%CIs) of highest versus lowest categories of neutrophil counts were 1.32 (1.20, 1.45) for risk of CVD incidence, 1.61 (1.23, 2.11) for all-cause mortality, 1.71 (1.45, 2.01) for CVD mortality, and 1.68 (1.17, 2.40) for non-CVD mortality. Further, per 1 SD increase of neutrophil counts was associated with a 4%, 12%, 14%, and 24% higher risk for CVD events, all-cause mortality, CVD mortality, and non-CVD mortality, respectively. In addition, a secondary dose-response analysis revealed a non-linear association of neutrophil counts with risk of CVD events (P_{non-linearity} = 0.01), but a linear positive association with CVD mortality (P_{non-linearity} = 0.87). The pooled associations of neutrophil counts with CVD risk, and all-cause, CVD, and non-CVD mortality did not differ by age, sex, region, and follow-up duration.
Conclusions Higher neutrophil counts were associated with a substantially higher risk of CVD events and all-cause, CVD, and non-CVD mortality.