Prior Heart Attack Research Articles

Prevalence, Patient Awareness, Treatment, and Control of Hypertension in Canadian Adults With Common Comorbidities

BackgroundWhether certain medical conditions are associated with blood pressure (BP) treatment and control is unclear. MethodsUsing the Canadian Health Measures Survey (2007-2019), BP was assessed according to the presence of selected comorbidities, including prior heart attack or stroke, dyslipidemia, chronic kidney disease, diabetes mellitus, obstructive sleep apnea, and overweight or obesity. ResultsA total of 5,841,453 people, representing 23.0% (95% confidence interval [CI] 21.7%-24.2%) of Canadian adults, were hypertensive. The adjusted odds ratio (aOR) of having hypertension treated and controlled was higher in people with the following conditions, as compared to people without these conditions: a prior heart attack or stroke (aOR 3.15; 95% CI 2.31-4.31); dyslipidemia (aOR 2.51; 95% CI 1.96-3.21); obstructive sleep apnea (aOR 1.95; 95% CI 1.19-3.21); overweight or obesity (aOR 1.51; 95% CI 1.18-1.94); chronic kidney disease (aOR 1.49; 95% CI 1.13-1.95); and diabetes (aOR 1.44; 95% CI 1.12-1.86). Individuals without any of these comorbidities were less likely to have BP that is treated and controlled (aOR 0.34; 95% CI 0.25-0.48). Moreover, the prevalence of BP treatment and control was low among many people without prior heart attack or stroke, even those with a moderate (aOR 0.25; 95% CI 0.17-0.37) or high (aOR 0.10; 95% CI 0.06-0.16) Framingham risk. ConclusionsLarge differences in levels of BP control exist across comorbidity profiles, and the greatest gaps are seen in individuals without recognized comorbidities, even those who have a moderate-to-high Framingham risk. Efforts to optimize BP control and narrow care gaps, especially in individuals without recognized comorbidities, are necessary to reduce the burden of cardiovascular disease and premature death in Canada.

Association Between Sleep Efficiency Variability and Cognition Among Older Adults: Cross-Sectional Accelerometer Study.

Sleep efficiency is often used as a measure of sleep quality. Getting sufficiently high-quality sleep has been associated with better cognitive function among older adults; however, the relationship between day-to-day sleep quality variability and cognition has not been well-established. We aimed to determine the relationship between day-to-day sleep efficiency variability and cognitive function among older adults, using accelerometer data and 3 cognitive tests. We included older adults aged >65 years with at least 5 days of accelerometer wear time from the National Health and Nutrition Examination Survey (NHANES) who completed the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Word-Learning subtest (CERAD-WL), and the Animal Fluency Test (AFT). Sleep efficiency was derived using a data-driven machine learning algorithm. We examined associations between sleep efficiency variability and scores on each cognitive test adjusted for age, sex, education, household income, marital status, depressive symptoms, diabetes, smoking habits, alcohol consumption, arthritis, heart disease, prior heart attack, prior stroke, activities of daily living, and instrumental activities of daily living. Associations between average sleep efficiency and each cognitive test score were further examined for comparison purposes. A total of 1074 older adults from the NHANES were included in this study. Older adults with low average sleep efficiency exhibited higher levels of sleep efficiency variability (Pearson r=-0.63). After adjusting for confounding factors, greater average sleep efficiency was associated with higher scores on the DSST (per 10% increase, β=2.25, 95% CI 0.61 to 3.90) and AFT (per 10% increase, β=.91, 95% CI 0.27 to 1.56). Greater sleep efficiency variability was univariably associated with worse cognitive function based on the DSST (per 10% increase, β=-3.34, 95% CI -5.33 to -1.34), CERAD-WL (per 10% increase, β=-1.00, 95% CI -1.79 to -0.21), and AFT (per 10% increase, β=-1.02, 95% CI -1.68 to -0.36). In fully adjusted models, greater sleep efficiency variability remained associated with lower DSST (per 10% increase, β=-2.01, 95% CI -3.62 to -0.40) and AFT (per 10% increase, β=-.84, 95% CI -1.47 to -0.21) scores but not CERAD-WL (per 10% increase, β=-.65, 95% CI -1.39 to 0.08) scores. Targeting consistency in sleep quality may be useful for interventions seeking to preserve cognitive function among older adults.

Generalisability of trials on antithrombotic treatment intensification in patients with cardiovascular disease

ObjectiveAssessment of generalisability of guideline-informing trials on antithrombotic treatment intensification to real-world patients with cardiovascular disease (CVD).MethodsInclusion and exclusion criteria of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS),...

Aspirin and Statins Reduce the Risk of Stroke in Women with Endometriosis (S3.002)

<h3>Objective:</h3> To determine (1) the risk of stroke in women with endometriosis and (2) the effect of aspirin and statins on that risk. <h3>Background:</h3> Endometriosis is an inflammatory chronic gynecologic condition that affects approximately 10% of reproductive aged women. Previous research suggests that endometriosis increases stroke risk, but the role of medications known to prevent stroke in modifying this risk is uncertain. <h3>Design/Methods:</h3> We retrospectively analyzed data from the California Teachers Study, a large prospective cohort of female teachers followed continuously since 1995, excluding those with prior stroke or heart attack. This analyses’ exposure was self-reported history of endometriosis, and the outcome was hospitalization for any stroke (ischemic stroke, intracerebral and subarachnoid hemorrhage). Study covariates were self-reported use of aspirin and statin, race-ethnicity, hysterectomy, and vascular risk factors: hypertension, diabetes mellitus, obesity, migraine, current or prior tobacco use, malignancy, and oral contraceptive use. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for stroke by age among women with and without history of endometriosis after adjustment for demographics and vascular risk factors. We examined association of aspirin and statin use with stroke among women with endometriosis. <h3>Results:</h3> Of 121,993 women, 13,938 (11.4%) reported a history of endometriosis. Women with endometriosis had slightly higher rates of vascular risk factors than women without endometriosis. Adjusted risk of stroke in the endometriosis group was higher than in the non-endometriosis group (HR 1.20, CI 1.09–1.28). Stroke occurred at a younger age among women with endometriosis (77.9 vs 80.2, p&lt;0.01). Within the endometriosis group, stroke risk in users of aspirin (HR 0.80, CI 0.69–0.92) or statins (HR 0.74, CI 0.62–0.88) was lower than that of non-users. <h3>Conclusions:</h3> In a large cohort study, history of endometriosis was associated with increased stroke risk and, among women with endometriosis, aspirin and statin use decreased this risk. <b>Disclosure:</b> Dr. Seitz has stock in Baxter International Inc. (&lt;0.0003% ownership), Bristol-Myers Squibb Company (&lt;0.0001%), Colgate-Palmolive Company (&lt;0.0002%), CVS Health Corporation (&lt;0.0002%), Johnson &amp; Johnson (&lt;0.00004%), Eli Lilly and Company (&lt;0.00005%), Proctor &amp; Gamble Company (&lt;0.00005%), UnitedHealth Group Incorporated (&lt;0.00002%), Walgreen Boots Alliance, Inc. (&lt;0.0002%), White Mountains Insurance (&lt;0.002%). Ms. Bull has stock in United Bank. Ms. Bull has received research support from Weill Cornell Medical College. Dr. Parikh has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for cases of neurological illness. The institution of Dr. Parikh has received research support from Leon Levy Foundation. The institution of Dr. Parikh has received research support from Florence Gould Foundation. The institution of Dr. Parikh has received research support from NY State Empire Clinical Research Investigator Program. The institution of Dr. Parikh has received research support from NIA. The institution of Dr. Parikh has received research support from Medtronic. Dr. Navi has nothing to disclose. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as a Consultant for GLG. Dr. Merkler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Neurohospitalist. Dr. Merkler has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for n/a. The institution of Dr. Merkler has received research support from AHA. The institution of Dr. Merkler has received research support from Weill Cornell Medical College. Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim. The institution of Dr. Liberman has received research support from NIH.

Validity of CHA2DS2-VASc score in patients with malignancies

Abstract Introduction Anticoagulation for patients with atrial fibrillation/flutter (AF) after risk stratification based on CHA2DS2-VASc score (congestive heart failure, hypertension, age group, Diabetes Mellitus, prior stroke, transient ischemic attack or thromboembolism, prior heart attack, peripheral artery disease or aortic plaque and patient's gender) has been the gold standard practice to prevent cerebrovascular accidents (CVA). Purpose Since patients with malignancies are at increased risk of thrombophilia, we tried to study if cancer patients with atrial fibrillation are at increased risk for CVA beyond what should be expected based on their comorbidities. Methods We used the Nationwide Readmissions Database (NRD) database for the years 2016–2019. First, we extracted all cases with a diagnosis of atrial fibrillation/flutter. Exclusion criteria included patients younger than 18-year-old. We studied the comorbidities and calculated CHA2DS2-VASc score. Then, we compared the risk for admission with an acute CVA in patients with and without any diagnosis of malignancies (solid cancer, leukemia, lymphoma or metastatic disease). Patients with carcinoma in situ were considered non-cancer patients. Corrected logistic regression and Chi-square tests using survey procedures in SAS 8.1 were applied to accommodate for complex sampling (Rao-Scott design). Results We identified 1,748,619 weighted admissions with AF equally distributed across the years. 5% were patients with malignancies. The mean age was 74-year-old for cancer patients and 71-year-old for non-cancer patients with quite equal gender distribution (43–49% were female). Patients with a diagnosis of cancer has high inpatient mortality (13%). Every additional point in CHA2DS2-VASc score was associated with increased odds of admission with CVA. Having a diagnosis of cancer was not associated with increased odds of admission with CVA (odd ratio for 95% confidence interval 1.0 [0.95–1.1]). Patients with history of VTE (assuming they are on anticoagulation) or who are on chronic anticoagulation have lower risk of admission with acute CVA if they have AF. Conclusions Although malignancies is associated with hypercoagulable status including higher risk for stroke, deep venous thrombosis and pulmonary embolism, our cross-sectional study indicates that CHA2DS2-VASc score is still a reliable tool for risk stratification in patients with atrial fibrillation. More longitudinal studies are needed. Funding Acknowledgement Type of funding sources: None.

Longitudinal association of handgrip strength with all-cause and cardiovascular mortality in older adults using a causal framework.

To date, there is no study addressing the time-varying confounding bias in the association of handgrip strength (HGS) with all-cause or cardiovascular mortality. Therefore, we conducted marginal structural models (MSM) to provide causal estimations on the associations of HGS with all-cause and cardiovascular mortality in a representative sample of adults aged 50years or older. Data from 29 countries including 121,116 participants (276,994 observations; mean age 63.7years; 56.3% women) free from prior heart attack or stroke were retrieved from consecutive waves of the Survey of Health, Ageing and Retirement in Europe (SHARE). During a median of 7.7years follow-up (interquartile range 3.8-11.8) and 1,009,862 person-years, 6407 participants (5.3%) died due to all causes, and 2263 (1.9%) died due to cardiovascular diseases. Using repeated measures of handheld dynamometry, we determined absolute and relative to body mass index HGS of each participant. We applied adjusted MSM to estimate hazard ratios (HRs) associated with changes over time in HGS addressing the time-varying confounding bias. An increase of 5kg in HGS was associated with a reduced risk of all-cause [HR 0.86, 95% confidence interval (CI), 0.86-0.90], overall cardiovascular (HR 0.86, 95% CI 0.82-0.86), heart attack (HR 0.90, 95% CI 0.86-0.95), and stroke (HR 0.86, 95% CI 0.82-0.90) mortality. The associations of relative HGS were of stronger magnitude in all cases. Our findings provide critical evidence on the importance of increasing general muscle strength in older adults to reduce mortality risk, particularly concerning cardiovascular causes.

Long-Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS-TIMI 54 Trial.

BackgroundCoronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long‐term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial.Methods and ResultsPatients in PEGASUS‐TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug‐eluting stent and first‐ versus later‐generation drug‐eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75–96) regardless of stent type (bare metal stent versus drug‐eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50–1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90–3.68).ConclusionsLong‐term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor.Registration Informationclinicaltrials.gov. Identifier: NCT01225562.

A tale of two patients.

Two patients come to the emergency department. One flies two hours from a different state. The other drives four hours from a different county. Both seek care at our hospital for chest pain. I am the medical student who sees them both. Chest pain is one of my favorite differentials, so I see both patients, one after the other. Both are men in their 70s, with a history of a prior heart attack status post–coronary artery bypass grafts, high blood pressure, and high cholesterol. Both dread they are having another heart attack. And both describe eerily similar symptoms: retrosternal chest pain that radiates up their esophagus and is worsened by both lying flat and eating. Their workups mirror each other. EKGs show no evidence of ischemia or a STEMI. Serial troponins come back within normal limits for both. I spit out my differential to the attending: serious causes include acute coronary syndrome, which I am reassured against by the negative EKG and serial troponins. Probable and treatable causes include GERD. My differential and assessment for each patient are identical: treat both patients for acid reflux and send home with strict return precautions given normal cardiac workup. But one patient gets admitted for observation. The other is discharged home. For all their similarities, these patients couldn't be more dissimilar. One is fluent in English, the other only speaks Spanish. One is, I am told, a VIP, or “very important patient,” and the other, by implication, is not. One is a donor, endowing the hospital with a large enough gift to not only warrant being named in the hospital's donor wall, but also a direct number to contact the head of cardiothoracic surgery during this admission. The other is a receiver, eligible for means tested programs, such as food stamps, but too traumatized by the public charge, even though it is no longer in effect, to seek help from these services. I take a deep breath and ask my team, what did I miss? Why were these two nearly identical patients managed so differently? But I know the answer. I simply wish it wasn't true. Because the idea that status is a contributing factor for my patients' diverging dispositions does not sit well with me. It seems to be the antithesis to what I envisioned medicine to be as a naive third-year medical student early in my clinical training. One intern assures me they treat everyone the same. And I don't doubt they believe that to be true. Another chimes in to add that every patient should be cared for as a VIP. My chief resident directly addresses the disparities between my two patients. “It's a necessary evil when donor dollars save lives.” Donor dollars save lives. But they also harm the lives of their donors. Research suggests that "very important patients" can influence health care providers to veer from standard of care, sometimes to their detriment.1 In a profession that prides itself on evidence-based practice, this specialized treatment seems counterintuitive. I wonder what my patients would have thought if the curtain concealing all the truths behind their medical decisions was pulled back. Would my discharged patient be relieved at avoiding an unnecessary stay? Upset at not being admitted? Unsurprised in the slightest by this sleight of hand? Would my admitted patient be equally unsurprised? Was this seemingly "above" standard of care the expectation? How would they feel knowing it could be substandard instead? I didn't have to wait long to have some of these questions answered. I had been virtually following both patients, devouring the admit and progress notes for confirmation that I was right, and dreading seeing a note for the patient we discharged that would suggest something more insidious than acid reflux. Both turned out to be GERD. The patient we discharged returned to the emergency department and was admitted for another medical concern. The patient we admitted was discharged after two days, the second at the family's insistence. They did not return during the remainder of my rotation. But another VIP came to our service. One who asked not to be treated differently, one who requested to share a room at our old hospital rather than its newer, billion-dollar sister. That patient left me with these haunting words: "I want the best care."

Efficacy and Safety of Long-Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta-analysis of Randomized Controlled Trials.

BackgroundLong‐term antithrombotic strategies for patients with chronic coronary syndrome with high‐risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta‐analysis to evaluate the efficacy and safety of long‐term antithrombotic strategies in patients with chronic coronary syndrome.Methods and ResultsFour randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS‐TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti‐platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta‐analysis showed that, compared with aspirin monotherapy, the ORs for trial‐defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80–0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78–1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64–0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,–0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial‐defined major bleeding were 2.15 (95% CI, 1.78–2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23–1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37–2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65–0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66–0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69–0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41–0.82) regimens.ConclusionsAll antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all‐cause mortality, rivaroxaban plus aspirin appears to be the preferred long‐term antithrombotic regimen for patients with chronic coronary syndrome and high‐risk factors.

Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long‐Term Ticagrelor in Stable Patients With Prior Myocardial Infarction

BackgroundTicagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy.Methods and ResultsPEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long‐term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3‐fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P=0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65–0.96; P interaction = 0.03).ConclusionsIn patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor.RegistrationURL https://www.clinicaltrials.gov/. Unique identifier: NCT01225562.

Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients With Cardiometabolic Disease.

Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality and has a known genetic contribution. We tested the performance of a genetic risk score for its ability to predict VTE in 3 cohorts of patients with cardiometabolic disease. We included patients from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trials (history of a major atherosclerotic cardiovascular event, myocardial infarction, and diabetes, respectively) who consented for genetic testing and were not on baseline anticoagulation. We calculated a VTE genetic risk score based on 297 single nucleotide polymorphisms with established genome-wide significance. Patients were divided into tertiles of genetic risk. Cox proportional hazards models were used to calculate hazard ratios for VTE across genetic risk groups. The polygenic risk score was compared with available clinical risk factors (age, obesity, smoking, history of heart failure, and diabetes) and common monogenic mutations. A total of 29 663 patients were included in the analysis with a median follow-up of 2.4 years, of whom 174 had a VTE event. There was a significantly increased gradient of risk across VTE genetic risk tertiles (P-trend <0.0001). After adjustment for clinical risk factors, patients in the intermediate and high genetic risk groups had a 1.88-fold (95% CI, 1.23-2.89; P=0.004) and 2.70-fold (95% CI, 1.81-4.06; P<0.0001) higher risk of VTE compared with patients with low genetic risk. In a continuous model adjusted for clinical risk factors, each standard deviation increase in the genetic risk score was associated with a 47% (95% CI, 29-68) increased risk of VTE (P<0.0001). In a broad spectrum of patients with cardiometabolic disease, a polygenic risk score is a strong, independent predictor of VTE after accounting for available clinical risk factors, identifying 1/3 of patients who have a risk of VTE comparable to that seen with established monogenic thrombophilia.

Analysis of heart rate dynamics based on nonlinear lagged returned map for sudden cardiac death prediction in cardiovascular patients

Sudden cardiac death (SCD) generally applied to an unpredicted death from a cardiovascular cause in a subject with or without preexisting heart disease. The main goal of this study was analyzing the Electrocardiogram (ECG) signal to design an algorithm to predict SCD risk. In this paper, ECG signals of 23 subjects (13 males, 8 females and 2 unknown), ranging from 17 to 89 years old necessary for the research were obtained from the Physionet database. For this purpose, we developed a new method to predict SCD, a 10-min prior heart attack using the return map. The aim of this study is a novel method based on Lag return map for in control patients and SCD classes. Return map with six different lags (1–6) was constructed in two-time intervals. After that, the non-linear features that include SD1, SD2, SD1/SD2 for each Lag was measured. The result shows that the rate of changes in SD1 and SD1/SD2 with increasing lags were increased significantly but in SD2 with increasing lags was decreased in two intervals. Statistical analysis indicates that return map parameters show changes in the transition to death episode (p < 0.05). Besides, there were significant changes (p < 0.01) in closer segments to death. In conclusion, it will be possible to predict SCD based on the nonlinear feature that can alarm doctors of an imminent SCD, helping them provide timely treatments that can increase the survival rate of patients and thus reduce the mortality rate.

Self-Efficacy, Perceived Barriers to Care, and Health-Promoting Behaviors Among Franco-Americans Across Cardiovascular Risk Factors: A Cross-Sectional Study

To assess the prevalence of perceived barriers to accessing health care services, self-efficacy, and health-promoting behaviors among Franco-Americans as a higher-risk group for familial hypercholesterolemia (FH), stratified by cardiovascular risk factors. Cross-sectional survey based on components of the Health Belief Model. Administered in-person at a Franco-American cultural center and online through mailing lists and social media platforms in the Northeastern United States. Franco-Americans and French Canadians (n = 170). Demographic and clinical characteristics (i.e. high cholesterol, prior heart attack or stroke, family history of atherosclerotic cardiovascular disease (ASCVD), diagnosis of FH), perceived barriers to accessing health care services, self-efficacy, and health-promoting behaviors (i.e. taking lipid-lowering medications, seeing a cardiovascular specialist). In a cohort of Franco-Americans, 42 (25%) had both high cholesterol and family history of ASCVD. Among Franco-Americans with both cardiovascular risk factors, 22% had low self-efficacy and only 16% had discussed FH with their physician. Individuals with both risk factors were significantly more likely to report a concern over a future diagnosis as a barrier to accessing health care services when compared with those with neither risk factor (36% vs. 15%, p = 0.014). Overall, other prominent barriers to care included knowledge of when to seek help (27%) and a distrust in medicine (26%). Franco-Americans report significant barriers to accessing health care services. Our findings strengthen the case for developing focused public health strategies to raise awareness for FH, particularly among high-risk subpopulations with unmet cardiovascular needs.

Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease.

Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease. Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis. A set of 32 single-nucleotide polymorphisms associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. In 51 288 subjects across the 5 trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, a higher GRS was strongly and independently associated with increased risk for ischemic stroke (P trend=0.009). In comparison with individuals in the lowest third of the GRS, individuals in the middle and top tertiles of the GRS had adjusted hazard ratios of 1.15 (95% CI, 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed that the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted hazard ratio for the top versus lowest tertile of 1.27 (95% CI, 1.04-1.53), in comparison with an adjusted hazard ratio of 1.06 (95% CI, 0.81-1.41) in subjects with previous stroke. In an exploratory analysis of patients with atrial fibrillation and CHA2DS2-VASc score of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA2DS2-VASc score of 3. Across a broad spectrum of subjects with cardiometabolic disease, a 32-single-nucleotide polymorphism GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA2DS2-VASc scores, the GRS identified patients with risk comparable to those with higher CHA2DS2-VASc scores.

Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines

The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations. To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations. A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD). The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.

Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial.

BackgroundA proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest.Methods and ResultsThis prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76–1.10; P=0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63–0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57–1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56–2.04; P=0.84).ConclusionsIn patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias.Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01225562.

Gut Microbiota-Dependent Trimethylamine N-oxide and Cardiovascular Outcomes in Patients With Prior Myocardial Infarction: A Nested Case Control Study From the PEGASUS-TIMI 54 Trial.

BackgroundTrimethylamine N‐oxide (TMAO) may have prothrombotic properties. We examined the association of TMAO quartiles with major adverse cardiovascular events (MACE) and the effect of TMAO on the efficacy of ticagrelor.Methods and Results PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin ‐ Thrombolysis in Myocardial Infarction 54) randomized patients with prior myocardial infarction to ticagrelor or placebo (median follow‐up 33 months). Baseline plasma concentrations of TMAO were measured in a nested case‐control study of 597 cases with cardiovascular death, myocardial infarction, or stroke (MACE) and 1206 controls matched for age, sex, and estimated glomerular filtration rate [eGFR]. Odds ratios (OR) were used for the association between TMAO quartiles and MACE, adjusting for baseline clinical characteristics (age, sex, eGFR, region, body mass index, hypertension, hypercholesterolemia, diabetes mellitus, smoking, peripheral artery disease, index event, aspirin dosage and treatment arm), and cardiovascular biomarkers (hs‐TnT [high‐sensitivity troponin T], hs‐CRP [high‐sensitivity C‐reactive protein], NT‐proBNP [N‐terminal‐pro‐B‐type natriuretic peptide]). Higher TMAO quartiles were associated with risk of MACE (OR for quartile 4 versus quartile 1, 1.43, 95% CI, 1.06–1.93, P trend=0.015). The association was driven by cardiovascular death (OR 2.25, 95% CI, 1.28–3.96, P trend=0.003) and stroke (OR 2.68, 95% CI, 1.39–5.17, P trend<0.001). After adjustment for clinical factors, the association persisted for cardiovascular death (OR adj 1.89, 95% CI, 1.03–3.45, P trend=0.027) and stroke (OR adj 2.01, 95% CI, 1.01–4.01, P trend=0.022), but was slightly attenuated after adjustment for cardiovascular biomarkers (cardiovascular death: OR adj 1.74, 95% CI, 0.88–3.45, P trend=0.079; and stroke: OR adj 1.82, 95% CI, 0.88–3.78, P trend=0.056). The reduction in MACE with ticagrelor was consistent across TMAO quartiles (P interaction=0.92).ConclusionsAmong patients with prior myocardial infarction, higher TMAO levels were associated with cardiovascular death and stroke but not with recurrent myocardial infarction. The efficacy of ticagrelor was consistent regardless of TMAO levels.Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: PEGASUS‐TIMI 54, NCT01225562.

WHOLE-BODY MRI TO ASSESS SUBCLINICAL CARDIOVASCULAR DISEASE AND FRAILTY DEVELOPMENT

Cardiovascular disease (CVD) and frailty have been linked at the mechanistic and epidemiological levels. Our goal is to identify if subclinical markers such as atherosclerosis, body composition, and fibrofatty infiltration measured from non-contrast whole-body magnetic resonance imaging (MRI) are markers of physical frailty. Community dwelling older adults with frailty status ascertained by Fried measurement are being recruited from an aging studies registry. MRI is performed using a Canon Galan3T with dedicated coils. Preliminary analysis from 4 frail individuals (86±15 years, 3 female, BMI=22±3kg/m2) and 2 age-matched robust controls (86±1 years, 1 female, BMI=28±0.2kg/m2) is presented. Of 4 frail one had a prior heart attack; one was previously diagnosed with heart failure. Mean atheroma score from 28 vessel segments (0.42±0.26 vs 0.18±0.10) and aortic tortuosity (2.3±0.4 vs 2.1±0.1) were higher in frail compared to robust indicative of higher atherosclerotic burden and vascular stiffness. Mean subcutaneous and visceral adipose tissue volumes were lower in frail compared to robust. However, mean myocardial (1113±27 vs 1089±2), liver (729±92 vs 683±104) and skeletal muscle (1106±25 vs 1072±64) T1 times (milliseconds) were each higher indicative of greater diffuse interstitial fibrosis. Averaged intramuscular fat percent measured across the pelvis, forearm, pectus, thigh, and calf was higher in frail compared to robust (14.8±4.1% vs 8.5±2.3%) indicative of higher fatty infiltration. Although these early results do not reach statistical significance, they support further study to determine cardiovascular and tissue related differences between physically frail and robust older adults, which in turn may inform intervention developments for frailty and CVD.

Preventive Care: How Mammography Utilization Changes as Women Age.

To evaluate the impact of comorbid conditions and age on mammography use. We used data from the 2011 to 2015 Medical Expenditure Panel Survey, which contained records for 40,752 women over the age of 40. Use was defined as a mammogram within the previous 1 or 2 years, analyzed separately. A logit model was employed to evaluate associations between use and comorbidities and age. Statistical significance was defined by a P < .05 by two-sided test. Of the 36,575 women in our study sample, 45.9%, 43.6%, 3.9%, and 5.7% reported a history of hypertension (HTN), hyperlipidemia (HLD), prior heart attack (MI), and prior stroke, respectively. Among women without a comorbid condition, there was 47.3% annual mammography use. HTN and HLD were associated with increased use (2.5 and 6.8 percentage points [pp], P< .01). In comparison, prior MI was associated with decreased annual use (-8.2 pp, P < .01). Prior stroke was not significantly associated with annual mammography (-1.5 pp, P= .42). Results were similar for biennial use. The age trend in use showed that the age with maximum screening use was approximately 60 years. Mammography use was higher in patients with HTN and HLD and lower in patients with prior MI and stroke, which mayreflect differences in comorbidity-related general health care use. Use increased until it peaked around age 60. An understanding ofhow mammography use naturally evolves as people age may help better target specific populations and improve overall use of preventive care.

P2551A randomized, pharmacodynamic comparison of low dose ticagrelor (60mg bid) to low dose prasugrel (5mg od) in patients with prior myocardial infarction: the ALTIC-2 study

Abstract Background In patients with prior myocardial infarction (MI) and features of high ischemic and low bleeding risk, extending dual antiplatelet therapy beyond 1 year or reinitiating treatment is reasonable. A lower than the standard dose, namely ticagrelor 60mg bid instead of 90mg bid and prasugrel 5mg od instead of 10mg od, may be associated with reduced bleeding risk. In the Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial, ticagrelor 60mg bid reduced the ischemic events, at the cost of increased bleeding events. There is no data on the pharmacodynamic efficacy of ticagrelor 60mg bid over low dose prasugrel (5mg od). Purpose To compare platelet reactivity (PR) between prasugrel 5mg od and ticagrelor 60 mg bid in the chronic phase of stable post-MI patients. Methods The ALTIC-2 was a prospective, single-center, randomized, crossover study involving patients on aspirin 100mg od and PEGASUS-TIMI 54 characteristics: &gt;50 years old with MI 1–3 years earlier and at least one high risk feature (age &gt;65 years, diabetes mellitus, a second MI, multivessel disease, or renal dysfunction). After a 14-day washout period–if on P2Y12 receptor antagonist therapy-, patients were randomized to either ticagrelor 60mg bid or prasugrel 5mg od for 14 days, with a crossover directly to the alternate treatment for another 14 days. PR was assessed by the VerifyNow P2Y12 reaction assay in PRU at baseline, pre and post-crossover, 2 hours post last study-drug dose. Statistical analysis was performed with STATA13.0. Results We recruited 20 eligible patients (80% men, 40% diabetics, 65% smokers, 70% multivessel disease, with a mean age of 64.8±6.3 years) for participation in the study (10 in each treatment sequence). During pre-crossover period, in the group allocated first in prasugrel PR levels (mean ± standard deviation) decreased from 238.4±50 to 128±47 (p&lt;0.0001), while in the group allocated first in ticagrelor levels of PR decreased from 259.6±36 to 30.8±29 (p&lt;0.0001). At the end of the 2 treatments, PR levels decreased to 33±26 in the group allocated first in prasugrel (p=0.0001), while in the group allocated first in ticagrelor levels of PR increased to 136±61 (p=0.0001). Analysis of combined data of PR levels (pre- and post-crossover, primary endpoint) adjusted for baseline values and age showed a difference of PR levels (β: −103, 95% CI: −120 to −85) in favor of ticagrelor. A non-significant period effect was observed and no carry effect was found. The secondary endpoint of high PR (&gt;208 PRU) rate was 0% for ticagrelor and 5.0% for prasugrel. No patient exhibited a major bleeding event at either treatment group. Conclusions In patients with previous MI and at least one other high-risk feature, low dose of ticagrelor results in a significantly lower PR compared to prasugrel 5mg od. Acknowledgement/Funding National and Kapodistrian University of Athens