The increasing prevalence of childhood
hypertension constitutes an important risk factor for cardiovascular
disease (CVD), contributing to long-term morbidity and mortality and
imposing substantial healthcare costs.1
Among potential mechanisms, early-life immune activation, characterized
by low-grade inflammatory and immune-cell responses, may contribute to
endothelial dysfunction and vascular remodeling, initiating processes
that predispose individuals to long-term cardiovascular sequelae. We
recently reported transcriptional alterations indicative of cytotoxic (PRF1, GZMB, IL2RB) and inflammatory responses (IL1B, FOS) in blood from adolescents with elevated blood pressure (BP).2
This reflects circulating immune cell activation, but does not permit
tissue-specific attribution. Urinary proteins, in contrast, provide a
complementary downstream biological readout that may capture
inflammatory signals at the circulation-vascular/renal interface, and
thus may serve as noninvasive indicators of early target-organ-related
processes.Given the distinct pathophysiological characteristics and CVD risk profiles of the BP subphenotypes3,4—isolated
diastolic hypertension (IDH), isolated systolic hypertension, and
combined systolic and diastolic hypertension (SDH)—we hypothesize that
early-life BP-related immune activation is associated with endothelial
dysfunction, and subphenotype-specific subclinical inflammation before
the formal diagnosis of hypertension.IDH,
recently defined as a distinct entity in the 2023 European Society of
Hypertension guideline, remains insufficiently characterized in early
life.3
It is more prevalent in adolescents than in adults and often
underdiagnosed. Although its contribution to CVD sequelae remains
inconclusive,3 IDH has been shown to predict chronic kidney disease risk,4 supporting the investigation of IDH during adolescence.We
quantified 10 inflammatory protein markers (LEGENDplex Human Vascular
Inflammation Panel 1-U, BioLegend) in spot urine samples from
15-year-old adolescents of the GINIplus birth cohort study (n=3199;
ethical approvals: Bavarian Board of Physicians: 10090; Board of
Physicians of North-Rhine-Westphalia: 2010424/2015491; Figure [A]).
Participants reporting physician-diagnosed hypertension at the 20-year
follow-up or a urinary tract infection within 4 weeks before sampling
were excluded. After restricting analyses to individuals with complete
BP, protein, and confounder data, 1502 participants remained (Figure [A] and [B]). BP was measured twice on the right arm, and the mean of the 2 valid measurements was used.2
Elevated BP subphenotypes, isolated systolic hypertension, IDH, SDH
(≥P95th), and normotension (