ReviewFrontiers in cardiovascular medicine2026
The insulin resistance-systemic vascular resistance-isolated diastolic hypertension axis: a metabolic framework for an overlooked hypertension phenotype.
Review in Frontiers in cardiovascular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Isolated diastolic hypertension (IDH) is defined as elevated diastolic blood pressure (DBP) with systolic blood pressure (SBP) below guideline-specific thresholds for hypertension. IDH is more prevalent in young and middle-aged adults and generally declines with age, yet its prognostic significance and optimal management remain debated. Hemodynamically, IDH differs from isolated systolic hypertension in that it is typically characterized by increased systemic vascular resistance (SVR) with relatively preserved large-artery compliance, consistent with a resistance-vessel-dominant phenotype. Accumulating evidence links insulin resistance (IR) and compensatory hyperinsulinemia to mechanisms that promote SVR elevation. In this review, we propose an insulin resistance-systemic vascular resistance-IDH (IR-SVR-IDH) axis as a mechanistic and clinically actionable framework for a metabolically enriched subtype of IDH. We synthesize evidence across three interacting pathways: (i) neural mechanisms involving sympathetic activation and downstream renin-angiotensin-aldosterone system signaling; (ii) vascular mechanisms characterized by endothelial insulin resistance, impaired nitric oxide bioavailability, inflammation, and microvascular remodeling; and (iii) renal mechanisms related to preserved sodium-retaining effects of insulin, salt sensitivity, and volume expansion. Clinically, pragmatic IR surrogates-including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-glucose (TyG) index, and metabolic score for insulin resistance (METS-IR)-are associated with IDH risk and may facilitate metabolic enrichment and risk stratification. Emerging outcome data indicate that metabolic status modifies IDH-associated cardiovascular risk, underscoring the importance of integrated blood pressure and metabolic phenotyping. By integrating hemodynamic and metabolic characterization, this framework supports a precision-oriented approach to an often overlooked hypertension phenotype.
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