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1. CVD IN RESPIRATORY DIORDERS

2. Cardiovascular disease in COPD COPD is a serious public health concern and is frequently associated with CVD. When COPD is associated with CVD, there is reduced health status and increased hospitalization rate and mortality.

3. Link between CVDs and COPD COPD is characterized by an enhanced inflammatory response in the airways, parenchyma and pulmonary vasculature to inhaled substances such as cigarette smoke, particulate matter and air pollutants. Characterized by increased levels of inflammatory markers including C-reactive protein (CRP), IL-1, -6 and -8, fibrinogen, activated leukocytes and TNF-α, with evidence of oxidative stress

4. These cytokines are increased not only in the systemic circulation but also in sputum and bronchoalveolar lavage fluid of COPD patients, suggesting that a spillover of inflammatory mediators from the peripheral lung occurs. COPD and CVD share common cytokines and a similar inflammatory pathophysiology, a link that might be explained by two different views

5. Systemic inflammation may predispose to atherosclerotic plaques, which may justify the high prevalence of myocardial infarction (MI) in COPD patients.

6. Pathophysiological mechanisms leading to increased cardiovascular risk in COPD The two diseases share several common risk factors, and chronic cigarette smoking is undoubtedly the most commonly encountered and identifiable, with ageing increasing the propensity to stroke. Smoking is a widely recognised risk factor for atherosclerosis and atherosclerotic plaque rupture and thus is implicated in the development of HF and CAD.

7. Inhalation of noxious gases and biomass fuel exposure are major factors in persistent lung and arterial wall inflammatory responses, which cause airflow obstruction and promote atherosclerosis and coronary plaque instability. Arterial stiffness, which is a pathophysiological condition common to both CVD and COPD, is a potential predictor of CVD risk in COPD patients.

8. Hypoxia, either sustained in severe COPD or intermittent during exercise or COPD exacerbations, is considered another important factor contributing to CVD risk. Hypoxia induces systemic inflammation and oxidative stress, increases the production of foam cells, upregulates cellular adhesion molecules in endothelial cells and increases CRP levels.

9. In COPD patients, hypoxemia may cause pulmonary vascular remodeling and vasoconstriction, leading to right ventricular diastolic dysfunction. Impairment of the right ventricle may increase pulmonary vascular resistance, which in turn may displace the interventricular septum to the left ventricle and affect ventricular filling, stroke volume and cardiac output.

10. Impact of CVD in COPD patients COPD and CVD share recognized risk factors such as ageing, tobacco smoke, reduced lung function and obesity with no differences in sex for the association with all CVDs,except for angina, CAD and MI, which were found to correlate more with women than with men COPD patients have a 2–5-fold increased risk of CAD, cardiac dysrhythmia, HF, pulmonary vascular disease and peripheral vascular disease (PVD).

11. Biomarkers and predictive models of cardiovascular risk in COPD patients

12. Conclusion CVEs still account for a large proportion of deaths among COPD patients. CVDs often remain asymptomatic, especially in COPD patients whose symptoms can be attributed to the underlying lung disease. A common background of low-grade systemic inflammation links the two disorders, triggered by various stimuli such as air pollutants and cigarette smoke. New applicable approaches and predictive biomarkers are needed to stratify COPD patients at risk for CVEs in order to provide effective and reliable screening procedures .

13. Choose treatment for asthma or COPD in the presence of CVD

14. Risks Benefits

15. The impact of cardiovascular drugs on the lung

16. Risks Benefits

17. Potential mechanisms behind the association of asthma and CAD

18. The role of eosinophils in CAD Eosinophils are key cells in type 2 asthma and allergic disease and may have a n underestimated role in CVD eosinophils contributed to thrombus formation by producing thrombin in response to tissue factor and an active pro-coagulant phospholipid surface Furthermore, eosinophils may increase platelet adhesion to injured endothelium The histological analysis of tissue samples obtained through thrombus aspiration of AMI patients has shown a variable eosinophil infiltration.

19. IL-5, a key cytokine for the migration, activation and proliferation of eosinophils , has also been identified in the thrombi of these patients . These observations suggest that eosinophils may have an active role in the pathogenesis of CAD, particularly contributing to a pro-thrombotic state

20. Sex differences and the risk of CAD in asthma Asthmatic women have a greater mortality risk due to CVD compared with men . In particular, hormonal differences between the sexes may contribute to the immunological and inflammatory process of asthma and CVD . Oestrogen may influence the response to endothelial injury and may enhance pro-inflammatory cytokines and cells, including mast cells Macrophages express oestrogen receptors , which have a role in both asthma and the development of atherosclerotic plaque

21. Asthma and hypertension Patients with asthma have an increased risk of developing hypertension throughout their life compared with non-asthmatics. Conversely, hypertension may be a risk of developing asthma. The mechanisms behind this is likely to be multifactorial and related to socioeconomics , medication use, the presence of obesity, OSA, genetic determinants and many other factors . For example, the use of both ICSs and oral corticosteroids(OCSs ) appears to increase the likelihood of hypertension. Similarly , OCSs can lead to unfavourable metabolic consequences, such as diabetes and dyslipidaemia , and thus cause the endothelial dysfunction and vascular stiffness seen in these conditions, leading to dysregulation of vascular tone and increasing the odds of hypertension.

22. Conclusion Because of the heterogeneity of asthma, multiple mechanisms may be at play behind the associations between asthma and CVD. Emerging evidence suggests that eosinophils and other cellular lines may influence the development of atherosclerosis, but other factors such as smooth muscle hyperreactivity and endothelial dysfunction appear have a pathophysiological role. Other patient characteristics, such as female sex and age of onset of asthma, are relevant with regard to cardiovascular risk. Experts advocate that asthma should be considered a complex airways disease with implications beyond the pulmonary system and recommend a multisystem evaluation using a collaborative multispecialty approach . For now, asthma remains a largely under- recognised risk factor for CVD in medical practice.