The global syndemic of metabolic diseases in the young adult population: A consortium of trends and projections from the Global Burden of Disease 2000-2019.

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. RESULTS: In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. CONCLUSION: The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.

IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST Action.

Acute myocardial infarction (AMI) and the heart failure (HF) which may follow are among the leading causes of death and disability worldwide. As such, new therapeutic interventions are still needed to protect the heart against acute ischemia/reperfusion injury to reduce myocardial infarct size and prevent the onset of HF in patients presenting with AMI. However, the clinical translation of cardioprotective interventions that have proven to be beneficial in preclinical animal studies, has been challenging. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic in vivo preclinical assessment of the efficacy of promising cardioprotective interventions prior to their clinical evaluation. To address this, we propose an in vivo set of step-by-step criteria for IMproving Preclinical Assessment of Cardioprotective Therapies ('IMPACT'), for investigators to consider adopting before embarking on clinical studies, the aim of which is to improve the likelihood of translating novel cardioprotective interventions into the clinical setting for patient benefit.

Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.

Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

Invasive Assessment of the Coronary Microcirculation in Reperfused ST-Segment-Elevation Myocardial Infarction Patients: Where Do We Stand?

For patients presenting with an acute ST-segment-elevation myocardial infarction, the most effective therapy for reducing myocardial infarct size and preserving left ventricular systolic function is primary percutaneous coronary intervention (PPCI). However, mortality and morbidity remain significant. This is partly attributed to the development of microvascular obstruction, which occurs in around 50% of ST-segment-elevation myocardial infarction patients post-PPCI, and it is associated with adverse left ventricular remodeling and worse clinical outcomes. Although microvascular obstruction can be detected by cardiac imaging techniques several hours post-PPCI, it may be too late to intervene at that time. Therefore, being able to predict the development of microvascular obstruction at the time of PPCI may identify high-risk patients who might benefit from further adjuvant intracoronary therapies, such as thrombolysis, vasodilators, glycoprotein IIb/IIIa inhibitors, and anti-inflammatory agents that may reduce microvascular obstruction. Recent studies have shown that invasive coronary physiology measurements performed during PPCI can be used to assess the coronary microcirculation. In this article, we provide an overview of the various invasive methods currently available to assess the coronary microcirculation in the setting of ST-segment-elevation myocardial infarction, and how they could potentially be used in the future for tailoring therapies to those most at risk.

ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies.

Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.

Rapid assessment of myocardial infarct size in rodents using multi-slice inversion recovery late gadolinium enhancement CMR at 9.4T.

BACKGROUND: Myocardial infarction (MI) can be readily assessed using late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Inversion recovery (IR) sequences provide the highest contrast between enhanced infarct areas and healthy myocardium. Applying such methods to small animals is challenging due to rapid respiratory and cardiac rates relative to T1 relaxation. METHODS: Here we present a fast and robust protocol for assessing LGE in small animals using a multi-slice IR gradient echo sequence for efficient assessment of LGE. An additional Look-Locker sequence was used to assess the optimum inversion point on an individual basis and to determine most appropriate gating points for both rat and mouse. The technique was applied to two preclinical scenarios: i) an acute (2 hour) reperfused model of MI in rats and ii) mice 2 days following non-reperfused MI. RESULTS: LGE images from all animals revealed clear areas of enhancement allowing for easy volume segmentation. Typical inversion times required to null healthy myocardium in rats were between 300-450 ms equivalent to 2-3 R-waves and ~330 ms in mice, typically 3 R-waves following inversion. Data from rats was also validated against triphenyltetrazolium chloride staining and revealed close agreement for infarct size. CONCLUSION: The LGE protocol presented provides a reliable method for acquiring images of high contrast and quality without excessive scan times, enabling higher throughput in experimental studies requiring reliable assessment of MI.