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Pubblicazioni recenti - cardiovascular risk
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Personalized Prediction of Cardiovascular Benefits and Bleeding Harms From Aspirin for Primary Prevention: A Benefit-Harm Analysis.
Ann Intern Med2019 Sep;():. doi: 10.7326/M19-1132.
Selak Vanessa, Jackson Rod, Poppe Katrina, Wu Billy, Harwood Matire, Grey Corina, Pylypchuk Romana, Mehta Suneela, Choi Yeun-Hyang, Kerr Andrew, Wells Sue,
Abstract
Background:
Whether the benefits of aspirin for the primary prevention of cardiovascular disease (CVD) outweigh its bleeding harms in some patients is unclear.
Objective:
To identify persons without CVD for whom aspirin would probably result in a net benefit.
Design:
Individualized benefit-harm analysis based on sex-specific risk scores and estimates of the proportional effect of aspirin on CVD and major bleeding from a 2019 meta-analysis.
Setting:
New Zealand primary care.
Participants:
245 028 persons (43.6% women) aged 30 to 79 years without established CVD who had their CVD risk assessed between 2012 and 2016.
Measurements:
The net effect of aspirin was calculated for each participant by subtracting the number of CVD events likely to be prevented (CVD risk score × proportional effect of aspirin on CVD risk) from the number of major bleeds likely to be caused (major bleed risk score × proportional effect of aspirin on major bleeding risk) over 5 years.
Results:
2.5% of women and 12.1% of men were likely to have a net benefit from aspirin treatment for 5 years if 1 CVD event was assumed to be equivalent in severity to 1 major bleed, increasing to 21.4% of women and 40.7% of men if 1 CVD event was assumed to be equivalent to 2 major bleeds. Net benefit subgroups had higher baseline CVD risk, higher levels of most established CVD risk factors, and lower levels of bleeding-specific risk factors than net harm subgroups.
Limitations:
Risk scores and effect estimates were uncertain. Effects of aspirin on cancer outcomes were not considered. Applicability to non-New Zealand populations was not assessed.
Conclusion:
For some persons without CVD, aspirin is likely to result in net benefit.
Primary Funding Source:
Health Research Council of New Zealand.
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Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.
Pregnancy Hypertens2019 Sep;18():49-54. doi: S2210-7789(19)30349-6.
Cooper Kylie M, Barrett Trace, McBride Carole A, Badger Gary J, Steiner Johannes, LeWinter Martin M, Bernstein Ira M,
Abstract
OBJECTIVES:
Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women.
STUDY DESIGN:
31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and ? stiffness measures as well as hemodynamic response to volume challenge. 22 underwent cardiac assessment via conventional and stress echocardiography with a focus on diastolic function utilizing tissue/pulse wave Doppler imaging and 3D speckle tracking. Bivariate associations between variables were evaluated using correlation coefficients (Pearson r) and Student's t-tests.
RESULTS:
No participants had echocardiographic values meeting criteria for overt diastolic dysfunction. Baseline global circumferential strain was significantly correlated with distensibility and ? stiffness (n?=?18, r?=?-0.61, p?=?0.007, n?=?18, r?=?0.56, p?=?0.01). Peak deceleration time was correlated with ?stiffness (n?=?9; r?=?0.80, p?=?0.01). Pulse wave velocity was not significantly correlated with cardiac measures (p?>?0.05). Family history of a first or second degree relative with myocardial infarction or hypertension was associated with decreased popliteal artery distensibility (p?=?0.02 and p?=?0.03, respectively).
CONCLUSIONS:
In healthy nulligravid women there is evidence that markers of decreased left ventricular relaxation are associated with increased peripheral vascular stiffness as is a family history of myocardial infarction or hypertension. These findings raise the possibility that the diastolic dysfunction and arterial stiffness observed in the setting of preeclampsia are driven by underlying properties present prior to pregnancy and contribute to lifetime cardiovascular risk.
Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
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Resilience among older cardiovascular disease patients with probable sarcopenia.
Arch Gerontol Geriatr2019 Aug;86():103939. doi: S0167-4943(19)30182-7.
Lee Szu-Ying, Tung Heng-Hsin, Peng Li-Ning, Chen Liang-Kung, Hsu Ching-I, Huang Yen-Ling,
Abstract
AIM AND OBJECTIVES:
The purpose of this study was to investigate the factors associated with resilience among probable sarcopenia older adults with cardiovascular disease.
INTRODUCTION:
Resilience has been reported to be positively correlated with the mental health and physical functioning of older adults. Previous research has found that the development of resilience constitutes a form of compensation for loss of physical health. It is important for older adults, especially those with other underlying conditions, such as cardiovascular disease and sarcopenia, to have the ability to overcome adversity during the aging process. Thus, resilience becomes a critical characteristic in achieving a better life.
METHODS:
A cross-sectional study design was used. A demographic questionnaire and the Chinese version of the Resilience Scale (CRS) were used to collect data. Multiple logistic regression was used to evaluate the predictors of low resilience.
RESULTS:
A total of 267 participants were recruited, including 126 females and 141 males. Of the participants, 56% of their scores indicated low resilience. Income, education level, exercise time, primary caregiver, and having hypertension were the predictors of resilience.
CONCLUSION:
The population with sarcopenia is increasing worldwide. Understanding resilience levels among older adults with probable sarcopenia is essential for promoting their mental health. Clinicians can use the results of this study to identify populations at high risk for low resilience and design specific interventions to promote better health outcomes.
Copyright © 2019 Elsevier B.V. All rights reserved.
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Derivation and Validation of an Early Diagnostic Score for Mediastinitis After Cardiothoracic Surgery.
Int J Infect Dis2019 Sep;():. doi: S1201-9712(19)30372-8.
Focaccia Siciliano Rinaldo, Medina Andrea Carolina Rodas, Bittencourt Márcio Sommer, Gualandro Danielle, Uezumi Kiyomi Kato, Santos Marcus Vinicius Barbosa, Pomerantzeff Pablo Maria Alberto, Scarpa Bruna, Leal Tatiana de Carvalho Andreuci Torres, Varejão Strabelli Tania Mara,
Abstract
OBJECTIVES:
The aim of this study was to elaborate on and validate a score for the early diagnosis of mediastinitis after cardiothoracic surgery.
METHODS:
Between 2007 and 2017, patients who experienced thoracic surgical-site infection after cardiothoracic surgery were enrolled. Laboratory, clinical, and chest CT findings were retrospectively analyzed. Patients were followed up until hospital discharge or intra-hospital death. Univariate and multivariate regression analyses were performed.
RESULTS:
950 surgical-site infections were found and analyzed (131 mediastinitis, 819 superficial/deep infections). Of the 131 mediastinitis episodes, 88% required surgical thoracic debridement,Staphylococcus aureus was identified in 43%, and overall mortality was 42%. The following variables were related to mediastinitis diagnosis: sternal diastasis (OR?=?2.5; 95% confidence interval [95%CI]: 1.2-5.3; P?=?0.012), bilateral pleural effusion (OR=1.9; 95%CI: 1.0-3.6; P?=?0.04), leukocyte count ?14,000cells/mm (Bitkover et al., 1999) (OR?=?2.5; 95%CI: 1.3-4.7; P?=?0.006), male sex (OR=2; 95%CI: 1.11-4; P?=?0.022), and positive blood culture (OR=3.0; 95%CI: 1.6-5.6; P?=?0.001). The score predicted with reasonable accuracy mediastinitis in the derivation cohort (AUC-ROC, 0.7476) and the validation cohort (AUC-ROC, 0.7149). Groups with high (31%) and low (5%) risk of mediastinitis were identified.
CONCLUSIONS:
An early diagnostic score in patients with surgical-site infection after cardiothoracic surgery identified groups with a low and high risk for mediastinitis.
Copyright © 2019. Published by Elsevier Ltd.
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The impact of physiological stress conditions on protein structure and trypsin inhibition of serine protease inhibitor Kazal type 1 (SPINK1) and its N34S variant.
Biochim Biophys Acta Proteins Proteom2019 Sep;():140281. doi: S1570-9639(19)30167-0.
Buchholz Ina, Nagel Felix, Klein Annelie, Wagh Preshit R, Mahajan Ujjwal M, Greinacher Andreas, Lerch Markus M, Mayerle Julia, Delcea Mihaela,
Abstract
One of the most common mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene is the N34S variant which is strongly associated with chronic pancreatitis. Although it is assumed that N34S mutation constitutes a high-risk factor, the underlying pathologic mechanism is still unknown. In the present study, we investigated the impact of physiological stress factors on SPINK1 protein structure and trypsin inhibitor function using biophysical methods. Our circular dichroism spectroscopy data revealed differences in the secondary structure of SPINK1 and N34S mutant suggesting protein structural changes induced by the mutation as an impairment that could be disease-relevant. We further confirmed that both SPINK1 (K of 0.15?±?0.06?nM) and its N34S variant (K of 0.08?±?0.02?nM) have similar binding affinity and inhibitory effect towards trypsin as shown by surface plasmon resonance and trypsin inhibition assay studies, respectively. We found that stress conditions such as altered ion concentrations (i.e. potassium, calcium), temperature shifts, as well as environmental pH lead to insignificant differences in trypsin inhibition between SPINK1 and N34S mutant. However, we have shown that the environmental pH induces structural changes in both SPINK1 constructs in a different manner. Our findings suggest protein structural changes in the N34S variant as an impairment of SPINK1 and environmental pH shift as a trigger that could play a role in disease progression of pancreatitis.
Copyright © 2019. Published by Elsevier B.V.
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A new approach to the diagnosis and treatment of atherosclerosis: the era of the liposome.
Drug Discov Today2019 Sep;():. doi: S1359-6446(19)30349-6.
Kiaie Nasim, Gorabi Armita Mahdavi, Penson Peter E, Watts Gerald, Johnston Thomas P, Banach Maciej, Sahebkar Amirhossein,
Abstract
The consequences of atherosclerotic cardiovascular disease (ASCVD) include myocardial infarction, ischemic stroke, and angina pectoris, which are major causes of mortality and morbidity worldwide. Despite current therapeutic strategies to reduce risk, patients still experience the consequences of ASCVD. Consequently, a current goal is to enhance visualization of early atherosclerotic lesions to improve residual ASCVD risk. The uses of liposomes, in the context of ASCVD, can include as contrast agents for imaging techniques, as well as for the delivery of antiatherosclerotic drugs, genes, and cells to established sites of plaque. Additionally, liposomes have a role as vaccine adjuvants against mediators of atherosclerosis. Here. we review the scientific and clinical evidence relating to the use of liposomes in the diagnosis and management of ASCVD.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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Redox signaling in ischemic postconditioning protection involves PKC? and Erk1/2 pathways and converges indirectly in Nrf2 activation.
Cell Signal2019 Sep;():109417. doi: S0898-6568(19)30213-X.
Díaz-Ruíz Jorge-Luis, Macías-López Arturo, Alcalá-Vargas Francisco, Guevara-Chávez José-Guadalupe, Mejía-Uribe Aída, Silva-Palacios Alejandro, Zúñiga-Muñoz Alejandra, Zazueta Cecilia, Buelna-Chontal Mabel,
Abstract
Ischemic-postconditioning (iPostC) exerts cardioprotection by preserving redox homeostasis in the reperfused heart. This protective effect has been associated with the activation of endogenous antioxidant response driven by transcription factor Nrf2 and with the activation of 'reperfusion injury salvage kinases' (RISK) as PI3K, PKC and Erk1/2. Redox homeostasis is essential for normal cell physiology since reactive oxygen species (ROS) are crucial for processes that involve protein signaling. Thus, it has become clear that not only the perturbation of redox balance to oxidative state is deleterious but also towards a reductive state contributing to pathogenesis of diseases. However, there is still a scarce knowledge about the role of ROS in the cardioprotective signals mediated by RISK in postconditioned hearts. Therefore, we studied the role of ROS as initiator of RISK signaling molecules in iPostC-conferred cardioprotection. With the aim to study the relationship between redox-dependent RISK activation and the downstream activation of the transcription factor Nrf2, we evaluated the effect of redox signaling disruption by the effect of ascorbic acid in iPostC hearts. Our results showed that PKC? and Erk1/2 activation is redox-dependent and that concurs downstream with Nrf2 deficient activation. Besides, using inhibitors we found that neither PI3K nor Erk1/2 are directly related with Nrf2 activation, indicating that these kinases have other targets. We conclude that redox signaling participates in cardioprotection triggered by iPostC through the action of kinase-dependent and -independent mechanisms and concurred with the downstream regulation of Nrf2-mediated antioxidant response to prolonged redox balance during long reperfusion.
Copyright © 2018. Published by Elsevier Inc.
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Significant Improvements in Mortality after the Fontan Operation in Children with Down Syndrome.
Ann Thorac Surg2019 Sep;():. doi: S0003-4975(19)31381-5.
Sarno Lauren A, Walters Henry L, Bondarenko Igor, Thomas Ronald, Kobayashi Daisuke,
Abstract
BACKGROUND:
Down syndrome (DS) is considered a risk factor for mortality associated with the Fontan operation. The objective was to show the contemporary short-term outcome of the Fontan operation for a functionally univentricular heart in patients with DS and non-DS, along with an analysis of significant predictors for in-hospital mortality.
METHODS:
This was a retrospective study using the Society of Thoracic Surgeons Congenital Database to assess in-hospital mortality and its predictors in patients with DS and non-DS undergoing the Fontan operation over 16 years (2001-2016). The primary outcome was in-hospital mortality. Statistical analysis was performed using univariable and multivariable logistic regression models.
RESULTS:
Our study cohort consisted of 12,074 patients (81 DS and 11,993 non-DS). The overall in-hospital mortality rate significantly improved in the recent era (2009 - 2016): 2.4% to 1.3%, p<0.001. The DS group had a higher in-hospital mortality rate (12.3% vs. 1.6%, p<0.001) with an odds ratio of 8.6 [95% confidence interval: 4.4 to 17.0]. The DS group had a higher 30-day mortality rate, a longer median post-operative length of stay, and a higher incidence of post-operative complications. The multivariable model showed that DS was the strongest predictor of in-hospital mortality with an odds ratio of 11.6 [95% confidence interval 5.1 to 26.4], adjusted for other significant variables including era effect, weight and primary cardiac diagnosis.
CONCLUSIONS:
The in-hospital mortality for the Fontan operation significantly improved in the contemporary era. Down syndrome was a significant risk factor for in-hospital morbidity and mortality associated with the Fontan operation.
Copyright © 2019. Published by Elsevier Inc.
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Effects of Consuming Almonds on Insulin Sensitivity and Other Cardiometabolic Health Markers in Adults With Prediabetes.
J Am Coll Nutr2019 Sep;():1-10. doi: 10.1080/07315724.2019.1660929.
Palacios Orsolya M, Maki Kevin C, Xiao Di, Wilcox Meredith L, Dicklin Mary R, Kramer Melvyn, Trivedi Rupal, Burton-Freeman Britt, Edirisinghe Indika,
Abstract
This study was designed to assess the effects of replacing high-carbohydrate (CHO) foods with raw almonds on insulin sensitivity and cardiometabolic health markers in overweight or obese adults with prediabetes. This randomized crossover study consisted of two 6-week dietary intervention periods, separated by a???4-week washout. Subjects incorporated 1.5?oz of raw almonds twice daily or isocaloric CHO-based foods into their diets, with instructions to maintain body weight. Dietary intakes as well as insulin sensitivity, CHO metabolism indices, lipoprotein lipids and particles, and inflammatory markers were assessed. Thirty-three subjects (17 male, 16 female), mean age 48.3?±?2.2?years and body mass index 30.5?±?0.7?kg/m, provided evaluable data. Compared to CHO, almonds resulted in significantly (?
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Internal Jugular Vein as Alternative Access for Implantation of a Wireless Pulmonary Artery Pressure Sensor.
Circ Heart Fail2019 Aug;12(8):e006060. doi: 10.1161/CIRCHEARTFAILURE.119.006060.
Abraham Jacob, McCann Patrick, Wang Lian, Schnell Heringer Amanda, Paulsen Jeff, Chappell Jay, Remick Joshua, Westerdahl Daniel, Lewis Rebecca, Callis Katherine, Spinelli Kateri J, Klein Liviu,
Abstract
BACKGROUND:
A wireless pulmonary artery pressure sensor (CardioMEMS) is approved for implantation via the femoral vein. The internal jugular vein (IJ) is an attractive alternative access route commonly used in pulmonary artery catheterization.
METHODS AND RESULTS:
Retrospective chart review was performed for all sensor implants from 10 providers at 4 centers from September 2016 to June 2018. To compare procedural outcomes and discharge efficiency between groups, multivariate analyses incorporating potential confounders were performed. Seventy-three (28%) patients had femoral access, and 189 (72%) had IJ access; demographics were similar between the groups. Complications, including one case of hematoma and 4 cases of mild hemoptysis, and 30-day mortality (2%-3%) did not differ between groups. Provider preference for IJ access substantially increased over time, with IJ accounting for 90% of cases in 2018. After risk-adjustment, IJ cases had 20% (5%-33%) shorter fluoroscopy time (=0.01) and 24% (7%-38%) lower contrast volume (=0.008). Compared with outpatient femoral cases, outpatient IJ cases had 62% (52%-69%) faster needle-to-door time and were 34 times (6-235) more likely to have same-day discharge (<0.001 for both).
CONCLUSIONS:
IJ access for CardioMEMS implant is a safe alternative associated with superior procedural and discharge outcomes. Implanters at 4 high-volume centers adopted IJ access as the preferred implant approach.
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Prognostic Value of Coronary Microvascular Function Measured Immediately After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: An International Multicenter Study.
Circ Cardiovasc Interv2019 Sep;12(9):e007889. doi: 10.1161/CIRCINTERVENTIONS.119.007889.
Nishi Takeshi, Murai Tadashi, Ciccarelli Giovanni, Shah Sonia V, Kobayashi Yuhei, Derimay François, Waseda Katsuhisa, Moonen Avalon, Hoshino Masahiro, Hirohata Atsushi, Yong Andy S C, Ng Martin K C, Amano Tetsuya, Barbato Emanuele, Kakuta Tsunekazu, Fearon William F,
Abstract
BACKGROUND:
The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease.
METHODS:
We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR?25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated.
RESULTS:
During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16-2.105; =0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11-2.28; =0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76-3.35; =0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67-6.63; =0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77-2.54; =0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99-2.43; =0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96-3.36; =0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events.
CONCLUSIONS:
IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.
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Effect of Baseline Left Ventricular Ejection Fraction on 2-Year Outcomes After Transcatheter Aortic Valve Replacement: Analysis of the PARTNER 2 Trials.
Circ Heart Fail2019 Aug;12(8):e005809. doi: 10.1161/CIRCHEARTFAILURE.118.005809.
Furer Ariel, Chen Shmuel, Redfors Bjorn, Elmariah Sammy, Pibarot Philippe, Herrmann Howard C, Hahn Rebecca T, Kodali Susheel, Thourani Vinod H, Douglas Pamela S, Alu Maria C, Fearon William F, Passeri Jonathan, Malaisrie S Chris, Crowley Aaron, McAndrew Thomas, Genereux Philippe, Ben-Yehuda Ori, Leon Martin B, Burkhoff Daniel,
Abstract
BACKGROUND:
Impaired left ventricular function is associated with worse prognosis among patients with aortic stenosis treated medically or with surgical aortic valve replacement. It is unclear whether reduced left ventricular ejection fraction (LVEF) is an independent predictor of adverse outcomes after transcatheter aortic valve replacement.
METHODS AND RESULTS:
Patients who underwent transcatheter aortic valve replacement in the PARTNER 2 trials (Placement of Aortic Transcatheter Valves) and registries were stratified according to presence of reduced LVEF (<50%) at baseline, and 2-year risk of cardiovascular mortality was compared using Kaplan-Meier methods and multivariable Cox proportional hazards regression. Of 2991 patients, 839 (28%) had reduced LVEF. These patients were younger, more often males, and were more likely to have comorbidities, such as coronary disease, diabetes mellitus, and renal insufficiency. Compared with patients with normal LVEF, patients with low LVEF had higher crude rates of 2-year cardiovascular mortality (19.8% versus 12.0%, <0.0001) and all-cause mortality (27.4% versus 19.2%, <0.0001). Mean aortic valve gradient was not associated with clinical outcomes other than heart failure hospitalizations (hazard ratio [HR], 0.99; CI, 0.99-1.00; =0.03). After multivariable adjustment, patients with reduced versus normal LVEF had significantly higher adjusted risk of cardiovascular death (adjusted HR, 1.42, 95% CI, 1.11-1.81; =0.005), but not all-cause death (adjusted HR, 1.20; 95% CI, 0.99-1.47; =0.07). When LVEF was treated as continuous variable, it was associated with increased 2-year risk of both cardiovascular mortality (adjusted HR per 10% decrease in LVEF, 1.16; 95% CI, 1.07-1.27; =0.0006) and all-cause mortality (adjusted HR, 1.09; 95% CI, 1.01-1.16; =0.02).
CONCLUSIONS:
In this patient-level pooled analysis of PARTNER 2 patients who underwent transcatheter aortic valve replacement, baseline LVEF was an independent predictor of 2-year cardiovascular mortality.
CLINICAL TRIAL REGISTRATION:
URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01314313, NCT02184442, NCT03222128, and NCT02184441.
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Association Between Low-Dose Rivaroxaban With or Without Aspirin and Ischemic Stroke Subtypes: A Secondary Analysis of the COMPASS Trial.
JAMA Neurol2019 Sep;():. doi: 10.1001/jamaneurol.2019.2984.
Perera Kanjana S, Ng Kelvin K H, Nayar Sumiti, Catanese Luciana, Dyal Leanne, Sharma Mukul, Connolly Stuart J, Yusuf Salim, Bosch Jackie, Eikelboom John W, Hart Robert G,
Abstract
Importance:
The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes.
Objective:
To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes.
Design, Setting, and Participants:
This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27?395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017.
Interventions:
Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day).
Main Outcomes and Measures:
Risk of ischemic stroke subtypes during follow-up.
Results:
A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P?=?.005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P?=?.006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P?=?.07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P?=?.61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P?=?.06) but was not associated with reducing other stroke subtypes.
Conclusions and Relevance:
For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice.
Trial Registration:
ClinicalTrials.gov identifier: NCT01776424.
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Change in Physical Activity and Cardiac Structure over 10 Years: The Multi-Ethnic Study of Atherosclerosis.
Med Sci Sports Exerc2019 Oct;51(10):2033-2040. doi: 10.1249/MSS.0000000000002027.
Florido Roberta, Zhao D I, Ndumele Chiadi E, Bluemke David A, Heckbert Susan R, Allison Matthew A, Ambale-Venkatesh Bharath, Liu Chia-Ying, Lima Joao, Michos Erin D,
Abstract
INTRODUCTION:
Physical activity (PA) is inversely associated with risk of heart failure and cardiovascular disease (CVD), whereas increased left ventricular (LV) mass and mass to volume (m:v) ratio are unfavorable CVD risk factors. We assessed whether changes in leisure time PA were associated with longitudinal changes in cardiac structure in a community-based population.
METHODS:
We included 2779 Multi-Ethnic Study of Atherosclerosis participants, free of baseline CVD, who had available data on PA and cardiac magnetic resonance imaging at examinations 1 (2000-2002) and 5 (2010-2012). Physical activity was measured by a Typical Week PA Survey and converted to MET-minutes per week of moderate+vigorous activity. We used linear mixed effect models to estimate the associations of baseline and change in PA with baseline and change in cardiac structure, adjusting for CVD risk factors and body size.
RESULTS:
At baseline, the mean age was 59 yr, 53% were women, and 58% of nonwhite race/ethnicity. During average 10-yr follow-up, and after accounting for baseline PA levels, the highest quintiles of PA increase were significantly associated with increases in LV mass (2.3 g; 95% confidence interval [CI], 0.4-4.2), LV end-diastolic volume (4.7 mL; 95% CI, 2.4-7.0), and stroke volume (3.3 mL; 95% CI, 1.6-5.1), but lower M:V ratio (-2.9; 95% CI, -5.0 to -0.8) compared with the lowest quintiles. Increasing exercise PA was associated with increases in LV diameter and reductions in M:V ratio, whereas occupational PA was associated with increases in m:v ratio. Increasing PA over 10 yr was also associated with greater risk of eccentric dilated LV hypertrophy at examination 5.
CONCLUSIONS:
After accounting for baseline PA, greater positive changes in leisure-time PA levels were associated with a more eccentric-type of LV remodeling pattern over 10 yr. The clinical implications of such findings remain to be determined.
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Diabetes Distress, Depressive Symptoms and Cardiovascular Health in Adults with Type 1 Diabetes.
Nurs Res2019 Sep;():. doi: 10.1097/NNR.0000000000000387.
McCarthy Margaret M, Whittemore Robin, Gholson Georica, Grey Margaret,
Abstract
BACKGROUND:
The prevalence of adults with type 1 diabetes (T1D) is increasing, and their risk of cardiovascular disease (CVD) is high. Comorbid diabetes distress and depressive symptoms may affect their cardiovascular health.
OBJECTIVES:
The purpose of this study was to describe the relationship between diabetes distress and depressive symptoms with cardiovascular health factors.
METHODS:
This was a cross-sectional survey of a sample of adults with T1D. Valid and reliable instruments were used to collect the data on sociodemographics, diabetes-related complications, psychological factors, and cardiovascular health factors. Independent sample t-tests, analysis of variance, chi-square analyses, and linear regression were used to compare the cardiovascular health factors among the three levels of diabetes distress scores and the two levels of depressive symptom scores.
RESULTS:
Our sample included 83 adults with a mean age of 45.2 years and a mean duration of T1D of 20 years. The majority scored low in the Diabetes Distress Scale while 18% scored moderate and 18% scored high. Twenty-two percent had increased levels of depressive symptoms. There were significant correlations between diabetes distress and fear of hypoglycemia, depressive symptom scores, hemoglobin A1c, and total cholesterol. Depressive symptom scores were significantly correlated with hemoglobin A1c. Hemoglobin A1c and total cholesterol were significantly higher in those with higher levels of diabetes distress. There were no significant differences in cardiovascular health between those who scored below or above the cut point for depressive symptoms, but there was a finding toward higher mean body mass index, hemoglobin A1c, and a lower weekly step count in those who had elevated depressive symptoms. In the linear regression, only diabetes distress was significantly associated with hemoglobin A1c.This is a sample with elevated diabetes distress and depressive symptoms, both of which may affect their risk of CVD.
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Cardiometabolic risk reduction after metabolic surgery.
Curr Opin Cardiol2019 Sep;():. doi: 10.1097/HCO.0000000000000683.
Pareek Manan, Bhatt Deepak L,
Abstract
PURPOSE OF REVIEW:
Metabolic surgery provides the largest and most durable weight loss in persons with obesity. There is abundant randomized evidence to show its superiority over medical treatment alone, in achieving improved glycemic control.
RECENT FINDINGS:
Recent trials have also demonstrated a significant reduction in cardiovascular risk factor burden, whereas data from observational studies suggest an ability to reduce overt cardiovascular events and mortality.
SUMMARY:
In this review, we briefly describe the surgical procedures involved and their indications. We further provide a summary of the effects of metabolic surgery on weight loss, glycemic control, and clinical outcomes.
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Multi-drug approaches to NASH: what's in the development pipeline?
Expert Opin Investig Drugs2019 Sep;():. doi: 10.1080/13543784.2020.1668926.
Johnston Michael P, Patel Janisha, Byrne Christopher D,
Abstract
Introduction The pandemic of obesity over the last two decades has triggered a rise in prevalence of non-alcoholic fatty liver disease (NAFLD). NAFLD is associated with liver-related- and cardiovascular complications. Despite this, the first licensed drug for NAFLD is yet to be approved. Given the scale of the problem and unmet needs, there is a myriad of agents in the development pipeline. Areas covered We discuss promising agents in early phase clinical trials and categorize these agents based on their action on steatosis, steatohepatitis and fibrosis. Furthermore, given the multisystemic nature of NAFLD, we consider the effects of these agents on the liver, their cardiometabolic effects, and the potential future strategies of combination therapies. Expert opinion The paradigm for the ideal drug is the targeting of both steatohepatitis and fibrosis and the amelioration of cardiometabolic risk factors. New drugs that confer benefit in NASH, must also be tested for their effects on T2DM and CVD. The treatment of NASH will become analogous to the treatment of hypertension; it is very likely that multiple classes of drugs targeting different mechanistic pathways will be necessary because no single agent is likely to control all aspects of this complex liver disease.
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Time in range is associated with carotid intima-media thickness in type 2 diabetes.
Diabetes Technol Ther2019 Sep;():. doi: 10.1089/dia.2019.0251.
Lu Jingyi, Ma Xiaojing, Shen Yun, Wu Qiang, Wang Ren, Zhang Lei, Mo Yifei, Lu Wei, Zhu Wei, Bao Yuqian, Vigersky Robert, Jia Weiping, Zhou Jian,
Abstract
BACKGROUND:
Time in range (TIR) is an emerging metric of glycemic control and was reported to be associated with microvascular complications of diabetes. We sought to investigate the association of TIR obtained from continuous glucose monitoring (CGM) with carotid intima-media thickness (CIMT) as a surrogate marker of cardiovascular disease (CVD).
METHODS:
Data from 2, 215 patients with type 2 diabetes were cross-sectionally analyzed. TIR of 3.9-10.0 mmol/L was evaluated with CGM. CIMT was measured using high-resolution B-mode ultrasonography and abnormal CIMT was defined as a mean CIMT ? 1.0mm. Logistic regression models were used to examine the independent association of TIR with CIMT.
RESULTS:
Compared with patients with normal CIMT, those with abnormal CIMT had significantly lower TIR (P < 0.001). The prevalence of abnormal CIMT progressively decreased across the categories of increasing TIR (P for trend <0.001). In a fully adjusted model controlling for traditional risk factor of CVD, each 10% increase in TIR was associated with 6.4% lower risk of abnormal CIMT. Stratifying the data by sex revealed that TIR was significantly associated with CIMT in males but not in females. In a subset of patients (n=612) with complete data on diabetic retinopathy and albuminuria, we found that the relationship between TIR and CIMT remained to be significant, regardless the status of microvascular complications.
CONCLUSIONS:
TIR is associated with CIMT in a large sample of patients with type 2 diabetes, suggesting a link between TIR and macrovascular disease.
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Double missense mutations in cardiac myosin-binding protein C and myopalladin genes: A case report with diffuse coronary disease, complete atrioventricular block, and progression to dilated cardiomyopathy.
Ann Noninvasive Electrocardiol2019 Sep;():e12687. doi: 10.1111/anec.12687.
Mastroianno Sandra, Palumbo Pietro, Castellana Stefano, Leone Maria Pia, Massaro Raimondo, Potenza Domenico Rosario, Mazza Tommaso, Russo Aldo, Castori Marco, Carella Massimo, Di Stolfo Giuseppe,
Abstract
Cardiomyopathies caused by double gene mutations are rare but conferred a remarkably increased risk of end-stage progression, arrhythmias, and poor outcome. Compound genetic mutations leading to complex phenotype in the setting of cardiomyopathies represent an important challenge in clinical practice, and genetic tests allow risk stratification and personalized clinical management of patients. We report a case of a 50-year-old woman with congestive heart failure characterized by dilated cardiomyopathy, diffuse coronary disease, complete atrioventricular block, and missense mutations in cardiac myosin-binding protein C (MYBPC3) and myopalladin (MYPN). We discuss the plausible role of genetic profile in phenotype determination.
© 2019 Wiley Periodicals, Inc.
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Diabetes-Associated Dementia Risk and Competing Risk of Death in the Three-City Study.
J Alzheimers Dis2019 Sep;():. doi: 10.3233/JAD-190427.
Frison Eric, Dufouil Carole, Helmer Catherine, Berr Claudine, Auriacombe Sophie, Chêne Geneviève,
Abstract
Diabetes is associated with a higher dementia and mortality risk. However, few studies have accounted for death when estimating the association between diabetes and dementia. We estimated absolute and relative risks of all-cause dementia according to diabetes exposure status in older adults while accounting for competing risk of death using illness-death models. Effect modification by specific characteristics (age, gender, education, cardiovascular risk factors, body mass index, cardiovascular history, depressive symptomatology, impaired renal function, and APOE?4 genotype) was also investigated. We analyzed the Three-City study data, a French population-based cohort of adults aged 65 years and above who were followed up for 12 years from 1999-2001. Among 8,328 participants selected in the analytical sample (median age, 73.3 years; 60.3% women), 809 (9.3%) presented with diabetes at baseline. Over a median follow-up period of 8.3 years, 836 participants developed incident dementia. Baseline diabetes was associated with a higher risk of dementia: hazard ratio, 1.79 [95% confidence interval, 1.46-2.19]. No effect modification was shown. Diabetes was associated with a higher 12-year absolute risk of dementia and a lower dementia-free life expectancy (e.g., 14.5% [11.2-18.1] versus 8.7% [7.6-10.2], and 13.4 [12.7-14.1] years versus 16.5 [16.0-17.1] years, respectively, for a 70-year-old woman with the highest level of education). These findings support the potential impact of preventing diabetes on reducing dementia risk in older adults, with a 2-3-year higher dementia-free life expectancy for individuals without diabetes, and inform the design of future interventional trials.
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