Beyond the Apnea-Hypopnea Index: Cardiovascular and Metabolic Phenotyping of Hypertensive Patients with Obstructive Sleep Apnea—A Narrative Review
Georgiana-Mihaela Cebuc Simeanu, Adina Dorina Glodeanu, Diana-Cristina Protasiewicz-Timofticiuc, Alina-Liliana Popa, Adina Mitrea, Ion-Cristian Efrem, Diana Clenciu, Adina-Andreea Mirea, Denisa-Maria Mitroi, Ioana-Gabriela Dragne, Bianca-Florentina Pîrvu, Delia-Viola Reurean-Pintilei, Beatrice Elena Vladu, Ana-Maria Efrem, Ștefania-Liana Nicolescu, Mircea-Catalin FortofoiuObstructive sleep apnea (OSA) is strongly associated with hypertension, yet the apnea–hypopnea index (AHI), while it defines the presence and frequency of respiratory events, predicts cardiovascular risk less reliably in the individual patient than metrics that incorporate the depth and duration of hypoxic exposure. Patients with comparable AHI values can differ substantially in nocturnal hypoxemia, sympathetic activation, ambulatory blood pressure behavior, and target-organ damage, exposing a persistent gap between respiratory classification and cardiovascular prognosis. This review synthesizes current evidence on the mechanisms linking OSA to hypertension, intermittent hypoxia, chemoreflex-mediated sympathetic overactivity, renin–angiotensin–aldosterone system activation, hypoxia-associated insulin resistance and examines emerging metrics, including hypoxic burden, oxygen desaturation index, and ambulatory blood pressure monitoring, that capture cardiovascular risk more accurately than AHI alone. We describe six cardiovascular phenotypes of hypertension in OSA: resistant, nocturnal, non-dipping/reverse-dipping, masked, and morning-surge hypertension, alongside hypertension-mediated target-organ damage, each with distinct mechanisms, prognosis, and treatment response. Because intermittent hypoxia and sympathetic activation are also implicated in insulin resistance and MASLD, this shared metabolic pathway is integrated throughout rather than treated as an incidental comorbidity. Building on this evidence, we propose a phenotype-oriented clinical framework spanning cardiovascular screening, multidomain phenotyping, risk stratification, and personalized therapy intended to complement, not replace, AHI-based diagnosis and current hypertension guidelines. This framework is presented as a conceptual, expert-derived proposal intended to structure clinical reasoning, and it has not been derived from or validated in an independent cohort. We conclude with future directions, including digital biomarkers, multimodal imaging, and artificial intelligence-assisted phenotyping, as pathways toward precision cardiovascular medicine in hypertensive patients with OSA.