Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice

Aims: Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via re- oxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite]. Methods: We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70ml-shot of active beetroot juice (Beet- It®) and either (i) 250 ml grapefruit juice (“Active Beet+GFJ”), or (ii) 250 ml water (Buxton®, “Active Beet+H2O”); or (iii) Placebo Beet+GFJ. Results: The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ versus Active Beet+H2O (P=0.02), and pulse pressure, PP (P=0.0003). Peak mean differences in SBP and PP were seen at T=5 hours: -3.3mmHg (95% CI -6.43 to -0.15) and at T=2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ versus Active Beet+H2O (P=0.006), as was salivary nitrite production (P=0.002) and saliva volume (-0.34 ml/min (95% CI -0.05 to - 0.68)). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2O (P=0.03). This article is protected by copyright. All rights reserved. Conclusions: Grapefruit juice enhanced beetroot juice’s effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension

Association of cardiometabolic microRNAs with COVID-19 severity and mortality

AIMS: Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. METHODS AND RESULTS: We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. CONCLUSION: Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response

COVID-19 and the heart

BACKGROUND: There is evidence for a bi-directional relationship between COVID-19 and the cardiovascular (CV) system. SOURCE OF DATA: Published literature. AREAS OF AGREEMENT: Pre-existing heart failure (HF) increases the risk of mortality with COVID-19. CV complications are recognized, including increased rates of acute coronary syndromes, HF, arrhythmia and myocarditis. Drugs targeting the angiotensin system are safe and may provide prognostic benefit. AREAS OF CONTROVERSY: Vaccination as a cause of myocarditis remains a key area of contention. GROWING POINTS: As the pandemic progresses, we are gaining more data about the long-term effects of COVID-19 on the CV system: long COVID, and medium-to-long-term increases in CV risk. AREAS TIMELY FOR DEVELOPING RESEARCH: Large-scale longitudinal studies will shed light on long-term CV outcomes with COVID-19. Furthermore, the differential effects of COVID-19 variants on the CV system must be investigated

Interaction Between Race, Ethnicity, Severe Mental Illness, and Cardiovascular Disease

Severe mental illnesses, such as schizophrenia or bipolar disorder, affect ≈1% of the population who, as a group, experience significant disadvantage in terms of physical health and reduced life expectancy. In this review, we explore the interaction between race, ethnicity, severe mental illness, and cardiovascular disease, with a focus on cardiovascular care pathways. Finally, we discuss strategies to investigate and address disparities in cardiovascular care for patients with severe mental illness

Severe mental illness: cardiovascular risk assessment and management

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.</p

Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19

BACKGROUND: The relative association between cardiovascular (CV) risk factors, such as diabetes and hypertension, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear. METHODS: We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1st March and 30th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained. RESULTS: Among 1721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients < 70 years of age (adjusted HR 2.43 [95% CI 1.16–5.07]), but not in those ≥ 70 years (aHR 1.14 [95% CI 0.77–1.69]). RF-CVD were not independently associated with mortality in either age group (< 70 y aHR 1.21 [95% CI 0.72–2.01], ≥ 70 y aHR 1.07 [95% CI 0.76–1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p < 0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group. Trial registration n/a. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02137-9