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Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

Objective: This study aims to examine the incidence of pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes, and their relationship in US Medicaid-funded women., Methods: Medicaid is a government-sponsored health insurance programme for low-income families in the USA. We report the incidence of pregnancy-related cardiometabolic conditions (hypertensive disorders and diabetes in, or complicated by, pregnancy) and severe cardiovascular outcomes (myocardial infarction, stroke, acute heart failure, cardiomyopathy, cardiac arrest, ventricular fibrillation, ventricular tachycardia, aortic dissection/aneurysm and peripheral vascular disease) among Medicaid-funded women with a birth (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code O80 or O82) over the period January 2015-June 2019, from the states of Georgia, Ohio and Indiana. In this cross-sectional cohort, we examined the relationship between pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes from pregnancy through to 60 days after birth using multivariable models., Results: Among 74 510 women, mean age 26.4 years (SD 5.5), the incidence per 1000 births of pregnancy-related cardiometabolic conditions was 224.3 (95% CI 221.3 to 227.3). The incidence per 1000 births of severe cardiovascular conditions was 10.8 (95% CI 10.1 to 11.6). Women with pregnancy-related cardiometabolic conditions were at greater risk of having a severe cardiovascular condition with an age-adjusted OR of 3.1 (95% CI 2.7 to 3.5)., Conclusion: This US cohort of Medicaid-funded women have a high incidence of severe cardiovascular conditions during pregnancy. Cardiometabolic conditions of pregnancy conferred threefold higher odds of severe cardiovascular outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The content of various tocopherols was determined in normal plasma and red blood cells. alpha-Tocopherol concentrations ranged form 6.6 to 15.0 (mean 9.6) mug/ml in plasma and from 0.9 to 1.8 (mean 1.4) mug/ml in red blood cells. gamma-Tocopherol ranged from 0.7 to 2.7 (mean 1.6) mug/ml in plasma and fron 0.1 to 0.4 (mean 0.24) mug/ml in red blood cells. Only a minute amount (smaller than 0.3 mug/ml) of each of alpha-tocotrienol, beta-tocopherol, gamma-tocotrienol and delta-tocopherol was found in plasma but none in red blood cells. No delta-tochotrienol was detected in either plasma or red blood cells. Of the total tocopherols, alpha form accounted 83 per cent in plasma and 87 per cent in red blood cells and gamma from represented 13 per cent in each system. The recovery of added 14-C-alpha-tocopherol averaged 87 per cent and 69 per cent, respectively, for plasma and red blood cells. All alpha-tocopherol in the red blood cells was found to be localized in the membrane fraction.