Independent and Joint Associations of Lipoprotein(a) and Homocysteine with Carotid–Femoral Pulse-Wave Velocity in Adults with Treated Hypertension: A Single-Centre Cross-Sectional Study

Background/Objectives: Carotid–femoral pulse-wave velocity (cfPWV) is the reference-standard non-invasive measure of central arterial stiffness and a validated marker of cardiovascular risk in hypertension. While lipoprotein(a) [Lp(a)] and homocysteine have each been implicated in vascular injury, their independent and combined associations with arterial stiffness in treated hypertension remain uncertain. In this study, we examined the associations of Lp(a), homocysteine, and peripheral artery disease (PAD) with cfPWV and assessed whether concomitant elevation of Lp(a) and homocysteine was associated with excess arterial stiffness. Methods: We conducted a single-centre, cross-sectional study of 366 consecutive adults with treated hypertension attending a tertiary hypertension centre and associated vascular service between February 2016 and October 2019. cfPWV was measured non-invasively through applanation tonometry using the SphygmoCor XCEL system. Multivariable robust linear regression was used to assess associations with cfPWV after adjustment for age, sex, body mass index, mean 24 h systolic blood pressure (BP), diabetes mellitus, chronic kidney disease, smoking status, low-density lipoprotein cholesterol, and PAD. Joint associations and interactions on multiplicative and additive scales were also evaluated. Results: Of 366 participants, 99 (27.0%) had high arterial stiffness, defined as cfPWV ≥ 10 m/s. After full adjustment, cfPWV increased by 0.13 m/s per 0.1 g/L increase in Lp(a) (95% CI, 0.08 to 0.18; p < 0.001) and by 0.26 m/s per 5 μmol/L increase in homocysteine (95% CI, 0.02 to 0.49; p = 0.03). Participants with concomitantly elevated Lp(a) and homocysteine had the highest adjusted cfPWV, with a mean difference of 1.56 m/s versus the low-Lp(a)/low-homocysteine group (95% CI, 1.00 to 2.13; p < 0.001). No meaningful multiplicative or additive interaction was observed. Conclusions: In adults with treated hypertension, higher Lp(a), higher homocysteine, and PAD were independently associated with greater central arterial stiffness. Concomitant elevation of Lp(a) and homocysteine identified participants with the highest cfPWV without evidence of synergistic interaction, supporting a complementary vascular-risk model.