The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.
INTRODUCTION
The Global Burden of Disease (GBD) is an international collaboration and the largest comprehensive investigation of global health disease burden ever conducted. Recently, we examined the shifting burden of neurosurgical disease in Vietnam and a handful of other nations. Our preliminary data supported the hypothesis that rapidly modernizing, middle-income nations have a particularly high burden of neurosurgical disease. To determine if this trend applied to middle-income nations at a global level, we extended our previous analysis to include all countries in the GBD database.
METHODS
Using GBD data, we abstracted data for death by cause and prevalence of years lived with disability (YLD) for common neurosurgical pathologies for every nation in the world. Using data from the Global Health Data Exchange, we determined GDP per capita for each nation. We constructed histograms to visually correlate the global burden of neurosurgical disease with GDP per capita.
RESULTS
A total of 16 of the 20 (80%) nations with the highest neurosurgical burden of disease were in the third income quartile, and 18 of the 20 (90%) nations with the highest burden of neurosurgical disease were in the middle 50% for YLD. In terms of deaths, 10 of the 20 (50%) nations were in the third quartile, and 16 of the 20 (80%) were in the middle 50%.
CONCLUSION
The training of a neurosurgeon requires a considerable investment of resources, making it difficult to address any quickly growing neurosurgical disease burden. Middle-income nations have both fewer neurosurgeons per capita and a greater neurosurgical disease burden compared to wealthier nations. Furthermore, neurosurgical pathologies that disproportionately afflict middle-income nations amplify the deleterious effects of any shortage of neurosurgeons. This trend is concerning, and suggests a need for greater international cooperation, focus, and investment in developing neurosurgical resources in middle-income and developing nations.
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