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Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.

Hypertension is the most significant risk factor for cardiovascular disease and mortality worldwide, affecting 1.3 billion adults. Global disparities in hypertension control are widening with low- and middle-income countries (LMIC) having the fastest growing rates of hypertension and low rates of control. Treatment for hypertension can be challenging, with multiple drug classes and dosing schedules. Combination antihypertensives have been suggested as a solution for their efficacy and potential to improve adherence. Global consumption of combination and non-combination antihypertensives across 75 countries and 2 regions from 2010 to 2021 was estimated using the IQVIA MIDAS database on pharmaceutical sales. Consumption rates were standardized using Standard Units (SUs) and analysed by high-income (HIC), upper-middle income (UMIC), and LMIC income classification. Global median consumption rate of all antihypertensives per 1000 inhabitants per day increased from 184.78 SUs in 2010 to 325.6 SUs in 2021, with HICs consistently having the highest rates. Median consumption rates of combination and non-combination antihypertensives increased across all country income groups but combination drugs were consumed at a lower rate and proportion. LMICs consumed a higher percentage of combination antihypertensives relative to non-combination (45.5%) than UMICs (24.3%) and HICs (24.4%) in 2021. While combination antihypertensives may be preferred for their potential for increased adherence and effectiveness, their global uptake is inconsistent. HICs consume less combination medication relative to non-combination, despite higher overall consumption rates of antihypertensives. LMICs show increasing use of combination medications, indicating a shift towards their use.