86 research outputs found

    Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?

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    Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i

    Peripheral Arterial Disease in Patients Presenting with Acute Coronary Syndrome in Six Middle Eastern Countries

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    To describe prevalence and impact of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS), data were collected over 5 months from 6 Middle Eastern countries. Patients were divided into 2 groups (with and without PAD). Out of 6705 consecutive ACS patients, PAD was reported in 177 patients. In comparison to non-PAD, PAD patients were older and more likely to have cardiovascular risk factors. They were more likely to have high Killip class, high GRACE risk score, and non-ST elevation ACS (NSTEACS) at presentation. Thrombolytics, antiplatelet use, and coronary intervention were comparable in both groups. When presented with ST-elevation myocardial infarction (STEMI), patients with PAD had worse outcomes, while in NSTEACS; PAD was associated with higher rate of heart failure in comparison to non-PAD patients. In diabetics, PAD was associated with 2-fold increase in mortality when compared to non-PAD (P = 0.028). After adjustment, PAD was associated with high mortality in STEMI (adjusted OR 2.6; 95% CI 1.23–5.65, P = 0.01). Prevalence of PAD in ACS in the Gulf region is low. Patients with PAD and ACS constitute a high risk group and require more attention. PAD in patients with STEMI is an independent predictor of in-hospital death

    The “obesity paradox” in patients with atrial fibrillation:Insights from the Gulf SAFE registry

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    BACKGROUND: The prognostic impact of obesity on patients with atrial fibrillation (AF) remains under-evaluated and controversial. METHODS: Patients with AF from the Gulf Survey of Atrial Fibrillation Events (Gulf SAFE) registry were included, who were recruited from six countries in the Middle East Gulf region and followed for 12 months. A multivariable model was established to investigate the association of obesity with clinical outcomes, including stroke or systemic embolism (SE), bleeding, admission for heart failure (HF) or AF, all-cause mortality, and a composite outcome. Restricted cubic splines were depicted to illustrate the relationship between body mass index (BMI) and outcomes. Sensitivity analysis was also conducted. RESULTS: A total of 1,804 patients with AF and recorded BMI entered the final analysis (mean age 56.2 ± 16.1 years, 47.0% female); 559 (31.0%) were obese (BMI over 30 kg/m(2)). In multivariable analysis, obesity was associated with reduced risks of stroke/systematic embolism [adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI), 0.18–0.89], bleeding [aOR 0.44, 95%CI, 0.26–0.74], HF admission (aOR 0.61, 95%CI, 0.41–0.90) and the composite outcome (aOR 0.65, 95%CI, 0.50–0.84). As a continuous variable, higher BMI was associated with lower risks for stroke/SE, bleeding, HF admission, all-cause mortality, and the composite outcome as demonstrated by the accumulated incidence of events and restricted cubic splines. This “protective effect” of obesity was more prominent in some subgroups of patients. CONCLUSION: Among patients with AF, obesity and higher BMI were associated with a more favorable prognosis in the Gulf SAFE registry. The underlying mechanisms for this obesity “paradox” merit further exploration

    Polyvascular Disease in Patients Presenting with Acute Coronary Syndrome: Its Predictors and Outcomes

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    We evaluated prevalence and clinical outcome of polyvascular disease (PolyVD) in patients presenting with acute coronary syndrome (ACS). Data for 7689 consecutive ACS patients were collected from the 2nd Gulf Registry of Acute Coronary Events between October 2008 and June 2009. Patients were divided into 2 groups (ACS with versus without PolyVD). All-cause mortality was assessed at 1 and 12 months. Patients with PolyVD were older and more likely to have cardiovascular risk factors. On presentation, those patients were more likely to have atypical angina, high resting heart rate, high Killip class, and GRACE risk scoring. They were less likely to receive evidence-based therapies. Diabetes mellitus, renal failure, and hypertension were independent predictors for presence of PolyVD. PolyVD was associated with worse in-hospital outcomes (except for major bleedings) and all-cause mortality even after adjusting for baseline covariates. Great efforts should be directed toward primary and secondary preventive measures

    Use of guideline-recommended management in established coronary heart disease in the observational DYSIS II study

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    Abstract Background Guidelines recommend lifestyle modification and medications to control risk factors in coronary heart disease (CHD). Using data from the observational DYSIS II study, we sought to evaluate the use of guideline-recommended treatments at discharge for acute coronary syndromes or in the chronic phase for CHD, and participation in rehabilitation/secondary prevention programs. Methods and results Between 2013 and 2014, 10,661 patients (3867 with ACS, 6794 with stable CHD) were enrolled in 332 primary and secondary care centers in 18 countries (Asia-Pacific, Europe, Middle East/Africa). Patients with incident ACS were younger and more likely to be smokers than patients with recurrent ACS or stable CHD (both p  Conclusions The high prevalence of risk factors in all CHD patients and reduced rates of secondary prevention medications in stable CHD offer areas for improvement. Translational aspects The findings of DYSIS II may reinforce the importance of adopting a healthy lifestyle and prescribing (by clinicians) and adhering (by patients) to evidence-based medications in the management of coronary heart disease, not only during the short-term but also over the longer term after a cardiac ischemic event. The results may help to increase the proportion of ACS patients who are referred to cardiac rehabilitation centres

    Demystifying Smoker's Paradox: A Propensity Score-Weighted Analysis in Patients Hospitalized With Acute Heart Failure.

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    Background Smoker's paradox has been observed with several vascular disorders, yet there are limited data in patients with acute heart failure (HF). We examined the effects of smoking in patients with acute HF using data from a large multicenter registry. The objective was to determine if the design and analytic approach could explain the smoker's paradox in acute HF mortality. Methods and Results The data were sourced from the acute HF registry (Gulf CARE [Gulf Acute Heart Failure Registry]), a multicenter registry that recruited patients over 10 months admitted with a diagnosis of acute HF from 47 hospitals in 7 Middle Eastern countries. The association between smoking and mortality (in hospital) was examined using covariate adjustment, making use of mortality risk factors. A parallel analysis was performed using covariate balancing through propensity scores. Of 5005 patients hospitalized with acute HF, 1103 (22%) were current smokers. The in-hospital mortality rates were significantly lower in current smoker's before (odds ratio, 0.71; 95% CI, 0.52-0.96) and more so after (odds ratio, 0.47; 95% CI, 0.31-0.70) covariate adjustment. With the propensity score-derived covariate balance, the smoking effect became much less certain (odds ratio, 0.63; 95% CI, 0.36-1.11). Conclusions The current study illustrates the fact that the smoker's paradox is likely to be a result of residual confounding as covariate adjustment may not resolve this if there are many competing prognostic confounders. In this situation, propensity score methods for covariate balancing seem preferable. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01467973.Gulf CARE (Gulf Acute Heart Failure Registry) is an investigator- initiated study conducted under the auspices of the Gulf Heart Association and funded by Servier, Paris, France; and (for centers in Saudi Arabia), by the Saudi Heart Association (The Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia [research group number: RG -1436- 013]). This does not alter our adherence to policies on sharing data and materials; and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The publication of this article was funded by the Qatar National Library

    Clinical presentation and outcomes of peripartum cardiomyopathy in the Middle East: a cohort from seven Arab countries

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    Aims: Published data on the clinical presentation of peripartum cardiomyopathy (PPCM) are very limited particularly from the Middle East. The aim of this study was to examine the clinical presentation, management, and outcomes of patients with PPCM using data from a large multicentre heart failure (HF) registry from the Middle East. Methods and results: From February to November 2012, a total of 5005 consecutive patients with HF were enrolled from 47 hospitals in 7 Middle East countries. From this cohort, patients with PPCM were identified and included in this study. Clinical features, in-hospital, and 12 months outcomes were examined. During the study period, 64 patients with PPCM were enrolled with a mean age of 32.5 ± 5.8 years. Family history was identified in 11 patients (17.2%) and hypertension in 7 patients (10.9%). The predominant presenting symptom was dyspnoea New York Heart Association class IV in 51.6%, class III in 31.3%, and class II in 17.2%. Basal lung crepitations and peripheral oedema were the predominant signs on clinical examination (98.2% and 84.4%, respectively). Most patients received evidence-based HF therapies. Inotropic support and mechanical ventilation were required in 16% and 5% of patients, respectively. There was one in-hospital death (1.6%), and after 1 year of follow-up, nine patients were rehospitalized with HF (15%), and one patient died (1.6%). Conclusions: A high index of suspicion of PPCM is required to make the diagnosis especially in the presence of family history of HF or cardiomyopathy. Further studies are warranted on the genetic basis of PPCM.Gulf CARE is an investigator-initiated study conducted under the auspices of the Gulf Heart Association and funded by Servier, Paris, France, and (for centres in Saudi Arabia) by the Saudi Heart Association [The Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia (Research Group Number RG-1436-013)]. This does not alter our adherence to policies on sharing data and materials, and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    World Heart Federation Cholesterol Roadmap 2022.

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    BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVD) including myocardial infarction, stroke and peripheral arterial disease continue to be major causes of premature death, disability and healthcare expenditure globally. Preventing the accumulation of cholesterol-containing atherogenic lipoproteins in the vessel wall is central to any healthcare strategy to prevent ASCVD. Advances in current concepts about reducing cumulative exposure to apolipoprotein B (apo B) cholesterol-containing lipoproteins and the emergence of novel therapies provide new opportunities to better prevent ASCVD. The present update of the World Heart Federation Cholesterol Roadmap provides a conceptual framework for the development of national policies and health systems approaches, so that potential roadblocks to cholesterol management and thus ASCVD prevention can be overcome. METHODS: Through a review of published guidelines and research papers since 2017, and consultation with a committee composed of experts in clinical management of dyslipidaemias and health systems research in low-and-middle income countries (LMICs), this Roadmap identifies (1) key principles to effective ASCVD prevention (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMICs; and (4) potential strategies for overcoming these. RESULTS: Reducing the future burden of ASCVD will require diverse approaches throughout the life-course. These include: a greater focus on primordial prevention; availability of affordable cholesterol testing; availability of universal cholesterol screening for inherited dyslipidaemias; risk stratification moving beyond 10-year risk to look at lifetime risk with adequate risk estimators; wider availability of affordable cholesterol-lowering therapies which should include statins as essential medications globally; use of adequate doses of potent statin regimens; and combination therapies with ezetimibe or other therapies in order to attain and maintain robust reductions in LDL-C in those at highest risk. Continuing efforts are needed on health literacy for both the public and healthcare providers, utilising multi-disciplinary teams in healthcare and applications that quantify both ASCVD risk and benefits of treatment as well as increased adherence to therapies. CONCLUSIONS: The adverse effects of LDL-cholesterol and apo B containing lipoprotein exposure are cumulative and result in ASCVD. These are preventable by implementation of different strategies, aimed at efficiently tackling atherosclerosis at different stages throughout the human life-course. Preventive strategies should therefore be updated to implement health policy, lifestyle changes and when needed pharmacotherapies earlier with investment in, and a shift in focus towards, early preventive strategies that preserve cardiovascular health rather than treat the consequences of ASCVD
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