The association of leptin and incident hypertension in the reasons for geographic and racial differences in stroke (REGARDS) cohort.

Leptin is an adipokine associated with obesity and with hypertension in animal models. Whether leptin is associated with hypertension independent of obesity is unclear. Relative to White adults, Black adults have higher circulating leptin concentration. As such, leptin may mediate some of the excess burden of incident hypertension among Black adults. REGARDS enrolled 30,239 adults aged ≥45 years from 48 US states in 2003-07. Baseline leptin was measured in a sex- and race-stratified sample of 4400 participants. Modified Poisson regression estimated relative risk (RR) of incident hypertension (new ≥140/≥90 mmHg threshold or use of antihypertensives) per SD of log-transformed leptin, stratified by obesity (BMI of 30 kg/m²). Inverse odds ratio weighting estimated the % mediation by leptin of the excess hypertension RR among Black relative to White participants. Among the 1821 participants without prevalent hypertension, 35% developed incident hypertension. Obesity modified the relationship between leptin and incident hypertension (P-interaction 0.006) such that higher leptin was associated with greater hypertension risk in the crude model among those with BMI < 30 kg/m², but not those with BMI ≥ 30 kg/m². This was fully attenuated when adjusting for anthropometric measures. In the crude model, Black adults had a 52% greater risk of incident hypertension. Leptin did not significantly mediate this disparity. In this national U.S. sample, leptin was associated with incident hypertension among non-obese but not obese adults. Future investigations should focus on the effect of weight modification on incident hypertension among non-obese adults with elevated leptin.