Plasma Metabolites Link Dietary Patterns to Stroke Risk

Abstract

Objective: While dietary intake is linked to stroke risk, surrogate markers that could inform personalized dietary interventions are lacking. We identified metabolites associated with diet patterns and incident stroke in a nested cohort from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Methods: Levels of 162 metabolites were measured in baseline plasma from stroke cases (n = 1,198) and random controls (n = 904). We examined associations between metabolites and a plant-based diet pattern previously linked to reduced stroke risk in REGARDS. Secondary analyses included 3 additional stroke-associated diet patterns: a Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Southern diet. Metabolites were tested using Cox proportional hazards models with incident stroke as the outcome. Replication was performed in the Jackson Heart Study (JHS). Inverse odds ratio-weighted mediation was used to determine whether metabolites mediated the association between a plant-based diet and stroke risk. Results: Metabolites associated with a plant-based diet included the gut metabolite indole-3-propionic acid (β = 0.23, 95% confidence interval [CI] [0.14, 0.33], p = 1.14 Â 10 À6 ), guanosine (β = À0.13, 95% CI [À0.19, À0.07], p = 6.48 Â 10 À5 ), gluconic acid (β = À0.11, 95% CI [À0.18, À0.04], p = 2.06 Â 10 À3 ), and C7 carnitine (β = À0.16, 95% CI [À0.24, À0.09], p = 4.14 Â 10 À5 ). All of these metabolites were associated with both additional diet patterns and altered stroke risk. Mediation analyses identified guanosine (32.6% mediation, p = 1.51 Â 10 À3 ), gluconic acid (35.7%, p = 2.28 Â 10 À3 ), and C7 carnitine (26.2%, p = 1.88 Â 10 À2 ) as mediators linking a plant-based diet to reduced stroke risk. Interpretation: A subset of diet-related metabolites are associated with risk of stroke. These metabolites could serve as surrogate markers that inform dietary interventions.

Trimethylamine N-Oxide and White Matter Hyperintensity Volume Among Patients With Acute Ischemic Stroke

“…The strengths of this study include the detailed phenotyping of both clinical characteristics and neuroimaging features. Furthermore, the method of metabolite measurement by our group, which uses a targeted metabolomic approach, allows the detection of metabolites with high sensitivity and specificity …”

“…In addition, the metabolite measurements were quality controlled and normalized across batches by including human pooled plasma samples at regular intervals of every 10 injections. All metabolite level values were rank-based inverse normal transformed before statistical analysis since they did not conform to a normal distribution …”

Association of Circulating Metabolites With Racial Disparities in Hypertension and Stroke in the REGARDS Study

“…11 Moreover, we extended these findings to show that many of these metabolites provided a link between dietary patterns and the risk of stroke. 18 In this study, we found that the association with gluconic acid was specific to Black participants. There was no difference in gluconic acid between all Black and White participants, suggesting that there is not an intrinsic biological difference.…”

“…11 Moreover, we extended these findings to show that many of these metabolites provided a link between dietary patterns and the risk of stroke. 18…”

“…This sampling design has been used and described in prior REGARDS studies. 11,[14][15][16][17][18] In this analysis, participants who were lost to follow-up, had a history of stroke at the time of enrollment or had no plasma available for metabolite measurements were excluded. Participants with hemorrhagic stroke or no record of stroke type were also excluded from the final analysis.…”