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Background
Lipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention.Objectives
This study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations.Methods
This study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells.Results
Overall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL.Conclusions
In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis. 相似文献Materials and methods: Narrative review.
Results: First, pain education is an effective but underused strategy for treating cancer related pain. Second, our neuro-immunological understanding of how stress can influence pain highlights the importance of integrating stress management into the rehabilitation approach for patients having cancer-related pain. The latter is supported by studies that have examined the effectiveness of various stress management programmes in this population. Third, poor sleep is common and linked to pain in patients following cancer treatment. Sleep deprivation results in a low-grade inflammatory response and consequent increased sensitivity to pain. Cognitive behavioural therapy for sleep difficulties, stress management and exercise therapy improves sleep in patients following cancer treatment. Finally, exercise therapy is effective for decreasing pain in patients following cancer treatment, and may even decrease pain-related side effects of hormone treatments commonly used in cancer survivors.
Conclusions: Neuro-immunology has increased our understanding of pain and can benefit conservative pain treatment for adults following cancer treatment.
- Implications for Rehabilitation
Pain education is effective for improving cancer pain; implementation of contemporary pain neuroscience into the educational programme seems warranted.
Various types of stress management are effective for treating patients following cancer treatment.
Poor sleep is common in patients following cancer treatment, and rehabilitation specialists can address this by providing exercise therapy, sleep hygiene, and/or cognitive behavioural therapy.
Exercise therapy is effective for decreasing pain in patients following cancer treatment, including the treatment of pain as a common side effect of hormone treatments for breast cancer survivors.