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Pubblicazioni recenti - cardiovascular risk
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Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus.
Diabetes Metab J2020 Oct;():. doi: 10.4093/dmj.2020.0057.
Jeon Ja Young, Ha Kyoung Hwa, Kim Dae Jung,
Abstract
Background:
Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.
Methods:
This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs).
Results:
After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.
Conclusion:
SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.
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Glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease. An expert consensus reported by the Chinese Diabetes Society and the Chinese Society of Endocrinology.
Diabetes Metab Res Rev2020 Oct;():e3416. doi: 10.1002/dmrr.3416.
Hong Tianpei, Su Qing, Li Xiaoying, Shan Zhongyan, Chen Li, Peng Yongde, Chen Liming, Yan Li, Bao Yuqian, Lyu Zhaohui, Shi Lixin, Wang Weiqing, Guo Lixin, Ning Guang, Mu Yiming, Zhu Dalong,
Abstract
Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF), or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF, or CKD. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Determinants of cardiovascular risk in 7,000 youth with type 1 diabetes in the Australasian Diabetes Data Network.
J Clin Endocrinol Metab2020 Oct;():. doi: dgaa727.
Couper Jenny J, Jones Timothy W, Chee Melissa, Barrett Helen L, Bergman Philip, Cameron Fergus, Craig Maria E, Colman Peter, Davis Elizabeth E, Donaghue Kim C, Fegan P Gerry, Hamblin P Shane, Holmes-Walker D Jane, Jefferies Craig, Johnson Stephanie, Mok Meng Tuck, King Bruce R, Sinnott Richard, Ward Glenn, Wheeler Benjamin J, Zimmermann Anthony, Earnest Arul,
Abstract
CONTEXT:
Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterised.
OBJECTIVE:
Primary aim was to measure the impact of BMI in youth with type 1 diabetes on cardiovascular risk factors. Secondary aim was to identify other determinants of cardiovascular risk.
DESIGN:
Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (IQR 4-11) years over 41 (IQR 29-56) visits until March 2019.
SETTING:
15 tertiary care diabetes centres in the Australasian Diabetes Data Network.
PARTICIPANTS:
aged 2 - 25 years at baseline, with at least two measures of BMI and blood pressure.
MAIN OUTCOME MEASURE:
Standardised systolic and diastolic blood pressure scores and non-HDL cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome.
RESULTS:
BMI z-score related independently to standardised blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4mmHg and an increase in non -HDL cholesterol (coefficient + 0.16mmol/L, 95%CI 0.13-0.18; p<0.001) and in LDL cholesterol. Females had higher blood pressure z-scores, higher non-HDL and LDL cholesterol, and higher urinary albumin/creatinine than males. Indigenous youth had markedly higher urinary albumin/creatinine (coefficient +2.15 mg/mmol, 95% CI 1.27-3.03; p<0.001) and higher non-HDL cholesterol than non-indigenous youth. Continuous subcutaneous insulin infusion was associated independently with lower non-HDL cholesterol and lower urinary albumin/creatinine.
CONCLUSIONS:
BMI had a modest independent effect on cardiovascular risk. Females and indigenous Australians in particular had a more adverse risk profile.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease.
Cardiorenal Med2020 Oct;():1-13. doi: 10.1159/000509741.
Verbrugge Frederik Hendrik, Martens Pieter, Testani Jeffrey M, Tang W H Wilson, Kuypers Dirk, Bammens Bert,
Abstract
BACKGROUND:
The evolution and prognostic impact of loop diuretic efficiency according to chronic kidney disease (CKD) severity is unclear.
METHODS:
This retrospective cohort study includes 783 CKD patients on oral loop diuretic therapy with a 24-h urine collection available. Acute kidney injury and history of renal replacement therapy were exclusion criteria. Patients were stratified according to Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate class. Loop diuretic efficiency was calculated as urine output, natriuresis, and chloruresis, each adjusted for loop diuretic dose, and compared among strata. Risk for onset of dialysis and all-cause mortality was evaluated.
RESULTS:
Loop diuretic efficiency metrics decreased from KDIGO class IIIB to IV in furosemide users and from KDIGO class IV to V with all loop diuretics (p value <0.05 for all comparisons). The correlation between loop diuretic efficiency and creatinine clearance was moderate at best (Spearman's ? 0.298-0.436; p value <0.001 for all correlations). During median follow-up of 45 months, 457 patients died (58%) and 63 received kidney transplantation (8%), while dialysis was started before in 328 (42%). All loop diuretic efficiency metrics were significantly and independently associated with both the risk for dialysis and all-cause mortality. In KDIGO class IV/V patients, low loop diuretic efficiency (i.e., urine output adjusted for loop diuretic dose ?1,000 mL) shortened median time to dialysis with 24 months and median time to all-cause mortality with 23 months.
CONCLUSION:
Low loop diuretic efficiency is independently associated with a shorter time to dialysis initiation and a higher risk for all-cause mortality in CKD.
© 2020 S. Karger AG, Basel.
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Statins and SARS-CoV-2 disease: Current concepts and possible benefits.
Diabetes Metab Syndr2020 Oct;14(6):2063-2067. doi: S1871-4021(20)30409-4.
Minz Madhu Mary, Bansal Manish, Kasliwal Ravi R,
Abstract
BACKGROUND AND AIMS:
Inflammation-mediated tissue injury is the major mechanism involved in the pathogenesis of coronavirus disease 2019 (COVID-2019), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Statins have well-established anti-inflammatory, anti-thrombotic and immuno-modulatory effects. They may also influence viral entry into human cells.
METHODS:
A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic.
RESULTS:
Statins interact with several different signaling pathways to exert their anti-inflammatory and vasculoprotective effects. They also variably affect cholesterol content of cell membranes and interfere with certain coronavirus enzymes involved in receptor-binding. Both these actions may influence SARS-CoV-2 entry into human cells. Statins also upregulate expression of angiotensin-converting enzyme 2 receptors on cell surfaces which may promote viral entry into the cells but at the same time, may minimize tissue injury through production of angiotensin [1-7]. The net impact of these different effects on COVID-19 pathogenesis is not clear. However, the retrospective clinical studies have shown that statin use is potentially associated with lower risk of developing severe illness and mortality and a faster time to recovery in patients with COVID-19.
CONCLUSIONS:
Early observations suggest beneficial effect of statin use on the clinical outcomes in COVID-19. Prospective randomized studies as well as well-designed laboratory studies are required to confirm these observations and to elucidate the mechanisms of such benefits, if proven.
Copyright © 2020. Published by Elsevier Ltd.
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A review of biosensor technologies for blood biomarkers toward monitoring cardiovascular diseases at the point-of-care.
Biosens Bioelectron2020 Sep;171():112621. doi: S0956-5663(20)30611-4.
Ouyang Mengxing, Tu Dandan, Tong Lin, Sarwar Mehenur, Bhimaraj Arvind, Li Chenzhong, Coté Gerard L, Di Carlo Dino,
Abstract
Cardiovascular diseases (CVDs) cause significant mortality globally. Notably, CVDs disproportionately negatively impact underserved populations, such as those that are economically disadvantaged and often located in remote regions. Devices to measure cardiac biomarkers have traditionally been focused on large instruments in a central laboratory but the development of affordable, portable devices that measure multiple cardiac biomarkers at the point-of-care (POC) are needed to improve clinical outcomes for patients, especially in underserved populations. Considering the enormity of the global CVD problem, complexity of CVDs, and the large candidate pool of biomarkers, it is of great interest to evaluate and compare biomarker performance and identify potential multiplexed panels that can be used in combination with affordable and robust biosensors at the POC toward improved patient care. This review focuses on describing the known and emerging CVD biosensing technologies for analysis of cardiac biomarkers from blood. Initially, the global burden of CVDs and the standard of care for the primary CVD categories, namely heart failure (HF) and acute coronary syndrome (ACS) including myocardial infarction (MI) are discussed. The latest United States, Canadian and European society guidelines recommended standalone, emerging, and add-on cardiac biomarkers, as well as their combinations are then described for the prognosis, diagnosis, and risk stratification of CVDs. Finally, both commercial in vitro biosensing devices and recent state-of-art techniques for detection of cardiac biomarkers are reviewed that leverage single and multiplexed panels of cardiac biomarkers with a view toward affordable, compact devices with excellent performance for POC diagnosis and monitoring.
Copyright © 2020 Elsevier B.V. All rights reserved.
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Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation.
Placenta2020 Oct;103():134-140. doi: S0143-4004(20)30418-5.
Chang Qing-Xian, Chen Xia, Ming-Xin Yang , Zang Nai-Liang, Li Le-Qian, Zhong Nanbert, Xia Lai-Xin, Huang Qi-Tao, Zhong Mei,
Abstract
BACKGROUNDS:
Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta.
METHODS:
Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 ?M). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate.
RESULTS:
Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo.
CONCLUSIONS:
Our ?ndings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Effects of potato resistant starch intake on insulin sensitivity, related metabolic markers and appetite ratings in men and women at risk for type 2 diabetes: a pilot cross-over randomised controlled trial.
J Hum Nutr Diet2020 Oct;():. doi: 10.1111/jhn.12822.
Sanders L M, Dicklin M R, Palacios O M, Maki C E, Wilcox M L, Maki K C,
Abstract
BACKGROUND:
The intake of certain types of resistant starch (RS) has been associated in some studies with increased whole-body insulin sensitivity. This randomised, cross-over pilot trial evaluated the effect of consuming cooked, then chilled potatoes, a source of RS, compared to isoenergetic, carbohydrate (CHO)-containing control foods, on insulin sensitivity and related markers.
METHODS:
Nineteen adults with body mass index 27.0-39.9 kg m consumed 300 g day RS-enriched potatoes (approximately two potatoes; ~18 g RS) or CHO-based control foods, as part of lunch, evening and snack meals, over a 24-h period. After an overnight fast, insulin sensitivity, CHO metabolism markers, free fatty acids, breath hydrogen levels and appetite were assessed for up to 5 h after the intake of a standard breakfast. The primary endpoint was insulin sensitivity, assessed with the Matsuda index. P < 0.05 (one-sided) was considered statistically significant.
RESULTS:
Insulin sensitivity was not significantly different between the potato and control conditions. The potato intervention resulted in higher postprandial breath hydrogen (P = 0.037), lower postprandial free fatty acid concentrations (P = 0.039) and lower fasting plasma glucose (P = 0.043) compared to the control condition. Fullness ratings were significantly lower after potato versus control (P = 0.002). No other significant effects were observed; however, there was a trend toward lower fasting insulin (P = 0.077) in the potato versus the control condition.
CONCLUSIONS:
The results of this pilot study suggest RS-enriched potatoes may have a favourable impact on carbohydrate metabolism and support the view that additional research in a larger study sample is warranted.
© 2020 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.
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Plasma Amino Acids metabolomic pattern in heart failure patients with either preserved (HFpEF) or reduced ejection fraction (HFrEF): The Relation to established risk variables and prognosis.
Biomed Chromatogr2020 Oct;():e5012. doi: 10.1002/bmc.5012.
Saleem Tahia H, Algowhary Magdy, Kamel Fatma Elzahraa M, El-Mahdy Reham I,
Abstract
Communication between amino acids (AAs) and heart failure (HF) is unclear. We evaluate the plasma metabolomic profile of AAs in HF and its subgroups and alliance with clinical features. This is a case-control study where 90 patients with HF, 63 with reduced ejection fraction (HFrEF), and 27 with preserved ejection fraction (HFpEF), were compared with 60 controls. Quantitative measurement of plasma concentrations of AAs metabolites was performed using AAs Analyzer. Compared with controls, HF patients had significantly higher levels of 9 AAs and significantly lower levels of 7 AAs. Leu, Phe, and Met were the independent predictors of HF that remained significant after adjustment for confounding factors in multivariate analysis. There was a significant difference in 10 AAs, and some clinical features between HFpEF, and HFrEF. The plasma levels of 6 AAs were significantly increased across the different NYHA class but they were not predicting EF and NYHA. There were significant associations between Leu, Phe, and Met with cardiovascular risk variables and prognosis. In conclusion, plasma Leu, Phe, and Met provide early prediction and prognostic values of HF. The plasma AAs could have significant impact on the risk-stratifying HFrEF, and HFpEF and NYHA functional class but do not predict them.
This article is protected by copyright. All rights reserved.
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Unprotected discharge: absence of stroke prevention strategies in patients with atrial fibrillation admitted for bleeding.
J Interv Card Electrophysiol2020 Oct;():. doi: 10.1007/s10840-020-00903-x.
Gorgis Sarah, Dabbagh Mohammed F, Mishra Kajali, Ahluwalia Guneet, Hana Aeman, Fram Georgi, Dhillon Dilshan, Lemor Alejandro, Khan Arfaat, Miller Daniel, Kaatz Scott, O'Neill William W, Wang Dee Dee,
Abstract
PURPOSE:
Patients with atrial fibrillation or flutter (AF) on anticoagulation (AC) for stroke prevention are at an increased risk of bleeding. A common clinical dilemma is deciding when to safely restart AC following a bleed. Although studies have shown better outcomes with re-initiation of AC after hemostasis, there are clinical barriers to restarting AC. Left atrial appendage occlusion (LAAO) is a safe and efficacious alternative for patients who are unable to tolerate AC following major bleeding. We aimed to evaluate the rate of stroke prevention strategies instituted at time of discharge in patients with AF on AC who had been hospitalized for a bleeding event.
METHODS:
We retrospectively identified patients with AF on AC admitted for bleeding between January 2016 and August 2019. The type of AC, form of bleeding, and CHADSVASc were collected. Stroke prevention strategies upon discharge and at 3 months were noted.
RESULTS:
One hundred seventy-four patients with AF on AC were hospitalized with a bleeding event, of which 10.9% died. Among patients who survived, AC was restarted in 45.2% of patients, 9.7% were referred for LAAO, and 45.1% were discharged without stroke prevention strategy. At 3 months, 32.6% of patients still had no documented stroke prophylaxis. Those referred for LAAO had, on average, higher CHADSVASc (5?±?1 vs 4?±?1, p?=?0.007).
CONCLUSIONS:
A significant number of patients with AF hospitalized for bleeding were discharged with no plan for stroke prophylaxis. Despite its safety and efficacy, LAAO appears to be an underutilized alternative in AF patients with high bleeding risk.
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The Association of Vitamin D and Vitamin K Status with Subclinical Measures of Cardiovascular Health and All-Cause Mortality in Older Adults: The Hoorn Study.
J Nutr2020 Oct;():. doi: nxaa293.
Dal Canto Elisa, Beulens Joline W J, Elders Petra, Rutters Femke, Stehouwer Coen D A, van der Heijden Amber A, van Ballegooijen Adriana J,
Abstract
BACKGROUND:
A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited.
OBJECTIVES:
Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians.
METHODS:
We performed an observational prospective study on 601 participants of the Hoorn Study (mean ± SD age: 70 ± 6 y, 50.4% women, BMI: 27.2 ± 4.0 kg/m2), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D?(stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders.
RESULTS:
Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m2.7; 95% CI: 1.8, 10.0 g/m2.7). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status.
CONCLUSIONS:
A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk.
© The Author(s) 2020. Published by Oxford University Press on behalf of American Society for Nutrition.
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Assessment of Dietary Acculturation in East Asian Populations: A Scoping Review.
Adv Nutr2020 Oct;():. doi: nmaa127.
Lee Sarah D, Kellow Nicole J, Choi Tammie S T, Huggins Catherine E,
Abstract
East Asian immigrants face multiple challenges upon arrival in their destination country, including an increased risk of future diabetes and cardiovascular disease development. The adoption of food and eating patterns of their host country (i.e., dietary acculturation) may contribute to this increased disease risk. To effectively examine the dietary acculturation-disease risk relationship in East Asian immigrants, sensitive tools are necessary; however, there has been no systematic review of the methods used to assess dietary acculturation in this population. A systematic scoping review of the literature was undertaken to address this gap. A systematic search was conducted in December 2019 and returned a total of 6140 papers. Manuscripts were screened independently by 2 reviewers, resulting in the final inclusion of 30 papers reporting on 27 studies. Robust measures of dietary acculturation were lacking, with only 6 studies using validated tools. Most studies used self-reported cross-sectional surveys to determine how the individual's diet had changed since immigrating, with responses provided on Likert scales. Only 3 quantitative longitudinal studies used prospective measures of diet change, through serial food-frequency questionnaires. Qualitative studies explored dietary acculturation and factors influencing change in diet through semi-structured interviews and focus groups. This review found there is no consensus in the literature on how to most effectively measure the magnitude and process of dietary acculturation in East Asian populations. There is a need for robust, longitudinal, and mixed-method study designs to address the lack of evidence and develop more comprehensive tools measuring dietary acculturation. Improving the assessment methods used to measure dietary acculturation is critical in helping to monitor the impact of interventions or policies aimed at reducing diet-related disease risk in East Asian immigrant populations.
© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.
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Extent of arterial calcification by conventional vitamin K antagonist treatment.
PLoS One2020 ;15(10):e0241450. doi: 10.1371/journal.pone.0241450.
Hasific Selma, Ųvrehus Kristian Altern, Gerke Oke, Hallas Jesper, Busk Martin, Lambrechtsen Jess, Urbonaviciene Grazina, Sand Niels Peter Rųnnow, Nielsen Jens Steen, Diederichsen Louise, Pedersen Kenneth Bruun, Carter-Storch Rasmus, Ilangkovan Nivethitha, Mickley Hans, Rasmussen Lars Melholt, Lindholt Jes Sandal, Diederichsen Axel,
Abstract
BACKGROUND AND AIMS:
Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD).
METHODS:
We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ?400) was investigated by ordered logistic regression adjusting for covariates.
RESULTS:
The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category.
CONCLUSIONS:
Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.
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Prescription-based prediction of baseline mortality risk among older men.
PLoS One2020 ;15(10):e0241439. doi: 10.1371/journal.pone.0241439.
Gedeborg Rolf, Garmo Hans, Robinson David, Stattin Pär,
Abstract
BACKGROUND:
Understanding the association between patients' history of prescribed medications and mortality rate could optimize characterization of baseline risk when the Charlson Comorbidity Index is insufficient.
METHODS:
Using a Swedish cohort of men selected randomly as controls to men with prostate cancer diagnosed 2007-2013, we estimated the association between medications prescribed during the previous year and mortality rates, using Cox regression stratified for age.
RESULTS:
Among the 326,450 older men with median age of 69 years included in this study, 73% were categorized as free of comorbidity according to the Charlson Comorbidity Index; however, 84% had received at least one prescription during the year preceding the follow-up. This was associated with a 60% overall increase in mortality rate (hazard ratio [HR] = 1.60, 95% confidence interval [CI] 1.56 to 1.64). Some drugs that were unexpectedly associated with mortality included locally acting antacids (HR = 4.7, 95% CI 4.4 to 5.1), propulsives (HR = 4.7, 95% CI 4.4 to 5.0), vitamin A and D (HR = 4.6, 95% CI 4.3 to 4.9), and loop diuretics, for example furosemide (HR = 3.7; 95% CI 3.6 to 3.8). Thiazide diuretics, however, were only weakly associated with a mortality risk (HR = 1.5; 95% CI 1.4 to 1.5). Surprisingly, only weak associations with mortality were seen for major cardiovascular drug classes.
CONCLUSIONS:
A majority of older men had a history of prescribed medications and many drug classes were associated with mortality rate, including drug classes not directly indicated for a specific comorbidity represented in commonly used comorbidity measures. Prescription history can improve baseline risk assessment but some associations might be context-sensitive.
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The effect of air-pollution and weather exposure on mortality and hospital admission and implications for further research: A systematic scoping review.
PLoS One2020 ;15(10):e0241415. doi: 10.1371/journal.pone.0241415.
Abed Al Ahad Mary, Sullivan Frank, Dem?ar Ur?ka, Melhem Maya, Kulu Hill,
Abstract
BACKGROUND:
Air-pollution and weather exposure beyond certain thresholds have serious effects on public health. Yet, there is lack of information on wider aspects including the role of some effect modifiers and the interaction between air-pollution and weather. This article aims at a comprehensive review and narrative summary of literature on the association of air-pollution and weather with mortality and hospital admissions; and to highlight literature gaps that require further research.
METHODS:
We conducted a scoping literature review. The search on two databases (PubMed and Web-of-Science) from 2012 to 2020 using three conceptual categories of "environmental factors", "health outcomes", and "Geographical region" revealed a total of 951 records. The narrative synthesis included all original studies with time-series, cohort, or case cross-over design; with ambient air-pollution and/or weather exposure; and mortality and/or hospital admission outcomes.
RESULTS:
The final review included 112 articles from which 70 involved mortality, 30 hospital admission, and 12 studies included both outcomes. Air-pollution was shown to act consistently as risk factor for all-causes, cardiovascular, respiratory, cerebrovascular and cancer mortality and hospital admissions. Hot and cold temperature was a risk factor for wide range of cardiovascular, respiratory, and psychiatric illness; yet, in few studies, the increase in temperature reduced the risk of hospital admissions for pulmonary embolism, angina pectoris, chest, and ischemic heart diseases. The role of effect modification in the included studies was investigated in terms of gender, age, and season but not in terms of ethnicity.
CONCLUSION:
Air-pollution and weather exposure beyond certain thresholds affect human health negatively. Effect modification of important socio-demographics such as ethnicity and the interaction between air-pollution and weather is often missed in the literature. Our findings highlight the need of further research in the area of health behaviour and mortality in relation to air-pollution and weather, to guide effective environmental health precautionary measures planning.
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Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl.
PLoS One2020 ;15(10):e0240166. doi: 10.1371/journal.pone.0240166.
Robinson Jennifer G, Jayanna Manju Bengaluru, Bairey Merz C Noel, Stone Neil J,
Abstract
BACKGROUND:
The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials.
OBJECTIVES:
Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy.
METHODS:
MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ?4%, 3-3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models.
RESULTS:
Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups.
CONCLUSIONS:
Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ?100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.
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COVID-19 myocarditis and prospective heart failure burden.
Expert Rev Cardiovasc Ther2020 Oct;():. doi: 10.1080/14779072.2021.1844005.
Shchedrygina Anastasia, Nagel Eike, Puntmann Valentina O, Valbuena-Lopez Silvia,
Abstract
INTRODUCTION:
COVID-19 is causing considerable morbidity and mortality worldwide. Serious respiratory complications aside, the heart is also frequently involved. The mechanisms and the extent of the myocardial injury, along with the short and long-term cardiovascular (CV) outcomes in COVID-19 survivors remain unclear.
AREAS COVERED:
myocardial injury has been found in a considerable proportion of hospitalized COVID-19 patients and is associated with a worse prognosis. The late onset of CV complications with myocarditis-like changes revealed by CMR have been reported in COVID-19 survivors. Previous observational studies on viral myocarditis provide evidence of a significant incomplete recovery with residual dysfunction and remodeling of left ventricle. Incomplete recovery is thought to be the result of persistent myocardial inflammation due to a post-viral autoimmune response. Considering the significant inflammatory nature of COVID-19, COVID-19 survivors may be at risk of developing persistent residual myocardial injury, the sequelae of which are unclear.
EXPERT COMMENTARY:
COVID-19 is an emerging threat for the heart. The extent of CV injury, along with the short and long-term sequelae, requires further investigation. The early detection of residual myocardial changes in COVID-19 survivors is of utmost importance in order to identify those patients at risk CV complication development.
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Serum concentration of vitamin A and its relationship with body adiposity, oxidative stress, and cardiovascular risk in women with recommended dietary intake of vitamin A.
Nutr Hosp2020 Oct;():. doi: 10.20960/nh.03129.
Bento Claudia, Matos Andrea, Cordeiro Adryana, Ramalho Andréa,
Abstract
Evidence indicates a role of vitamin A in the regulation of fat mass influencing obesity and cardiovascular diseases. A cross-sectional study in 200 women, paired by age and by the recommended dietary intake of vitamin A. Subjects were divided into four groups according to body mass index (BMI): 80 eutrophic (E), 40 overweight (OW), 40 class I obesity (OI) and 40 class II obesity (OII). Lipid and glycemic profiles were measured and oxidative stress was evaluated through serum concentrations of uric acid, glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBARS). The cutoff points for deficiency of serum retinol and ?-carotene levels were < 1.05 µmol/L and 40 µg/dL, respectively. For the recommended dietary intake of vitamin A it was 700 µg/day. Retinol and ?-carotene deficiency was found in the E group at 5 % and 15 %, respectively, reaching 77.5 % and 82.5 % in the OII group. A correlation was observed between serum concentrations of retinol and ?-carotene and glycemic, lipid, and markers of oxidative stress profiles in the groups studied. It was observed that OI and OII subjects who had retinol and ?-carotene deficiency presented a risk that was 16 and 20.7 times greater, respectively, of having a diagnosis with DM2 as compared to E subjects with adequate concentrations of vitamin A. Increased demand of vitamin A may be related to increased BMI, body adiposity, and oxidative stress even when a recommended intake of vitamin A is reached.
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Oxygen transport and utilisation during exercise in cystic fibrosis: Contributors to exercise intolerance.
Exp Physiol2020 Oct;():. doi: 10.1113/EP088106.
Saynor Zoe L, Gruet Mathieu, Rodriguez-Miguelez Paula, Harris Ryan A,
Abstract
NEW FINDINGS:
What is the topic of this review? This review highlights the central and peripheral mechanisms that alter oxygen transport and utilisation and thereby contribute to exercise limitation in people with cystic fibrosis, considering also viable therapeutic targets for intervention. What advances does it highlight? Although traditionally considered a respiratory condition, pathological intramuscular and cardiovascular changes in people with cystic fibrosis appear to be key determinants of exercise intolerance up until the later stages of respiratory disease. Even young, habitually active patients with normal lung function experience multisystemic abnormalities, which play a role in exercise intolerance.
ABSTRACT:
Cystic fibrosis (CF) is a complex condition, commonly associated with exercise limitation. The mechanisms responsible for this in CF are of interest, given that lower aerobic fitness is associated with an increased risk of being hospitalised with pulmonary exacerbation, a poorer quality of life and prognosis. Pathophysiological changes in lung function are considered central to CF, and may contribute to exercise limitation. However, it is now clear that the pathogenesis of exercise limitation in this population is multifactorial, with alterations in cardiovascular, muscle and pulmonary function contributing. Whilst some of these changes are attributable to respiratory disease per se, the CF transmembrane conductance regulator protein is also found in skeletal muscle and the vascular endothelium and can directly alter central and localised oxygen delivery, as well as the ability to effectively extract and utilise oxygen at the myocyte level. Since intense exercise poses considerable challenges to arterial oxygen content and/or blood flow and its supply to the working skeletal muscle, evaluating the exercise physiology of people with CF has helped us understand the mechanisms underlying exercise intolerance. Through several investigations over recent years, we have collectively demonstrated that people with CF exhibit reduced skeletal muscle oxygen extraction and utilisation during exercise, with a lesser contribution from haemodynamic or chronotropic mechanisms. Taken together, our findings highlight the importance of targeting mechanisms of skeletal muscle oxygen utilisation in CF to improve exercise tolerance and we offer potential therapeutic interventional strategies. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.
JAMA Netw Open2020 Oct;3(10):e2023242. doi: 10.1001/jamanetworkopen.2020.23242.
Khera Rohan, Pandey Ambarish, Ayers Colby R, Carnethon Mercedes R, Greenland Philip, Ndumele Chiadi E, Nambi Vijay, Seliger Stephen L, Chaves Paulo H M, Safford Monika M, Cushman Mary, Xanthakis Vanessa, Ramachandran Vasan S, Mentz Robert J, Correa Adolfo, Lloyd-Jones Donald M, Berry Jarett D, de Lemos James A, Neeland Ian J,
Abstract
Importance:
Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.
Objective:
To assess performance of the PCE across clinical BMI categories.
Design, Setting, and Participants:
This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37?311 participants. Data were analyzed from August 2017 to July 2020.
Exposures:
Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (?35).
Main Outcomes and Measures:
Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino ?2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE.
Results:
Among 37?311 participants (mean [SD] age, 58.6 [11.8] years; 21?897 [58.7%] women), 380?604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13?601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ?20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics.
Conclusions and Relevance:
These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.
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