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This study aims to evaluate the age- and sex-specific associations of comorbidities with stroke and MI and further calculate the population-attributable fractions (PAFs) of five comorbid diseases for stroke and myocardial infarction (MI) by age and sex. This is a prospective cohort study. This study leveraged data from a sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project. Participants aged 35–75 years without a prevalent stroke and MI were enrolled from January 2016 to December 2020, with follow-up through December 2021. Five common comorbidities were collected at baseline, and the study outcome was hospitalization for stroke and MI identified from the Inpatients Registry. Of 100,873 participants, the mean age was 54.2 (±10.2) years, 34.2% were ≥60 years old, and 60.8% were women. After a median follow-up of 3.52 years, 4156 participants had stroke/MI. The strengths of the associations between hypertension, diabetes, and obesity with stroke/MI were higher in younger individuals than in seniors, and obesity had a more hazardous impact on stroke/MI in men than in women. The five comorbidities collectively explained a higher population attributable fraction (PAF) for stroke/MI in the young group (51.5[46.9, 55.7] %) than in the senior group (41.3[37.0, 45.4] %), in men (45.6[40.9, 49.9] %) than in women (41.1[36.1, 45.7] %). Most of the common comorbidities were significantly associated with stroke and MI. Several age and sex differences in the impacts of comorbidities on stroke/MI were observed, highlighting the importance of age- and sex-specific preventive strategies to reduce premature stroke and MI. [Display omitted] [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. Patients with PCa receiving GnRH agonists or antagonists during 2013–2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACE PRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACE CVM , i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0–81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7–5.0 years), 1115 patients (45.0%) had MACE PRONOUNCE and 344 (13.9%) had MACE CVM. GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACE PRONOUNCE : Log-rank P = 0.308; MACE CVM : Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACE PRONOUNCE : Log-rank P = 0.569; MACE CVM : Log-rank P = 0.615). GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors. • GnRH agents may differ in cardiovascular safety. • 2479 prostate cancer patients receiving GnRH agonists or antagonist were studied. • GnRH antagonist may be associated with higher long-term cardiovascular risks. • Short-term cardiovascular risks did not differ between GnRH agonists and antagonists. • Those without cardiovascular risk factors had a larger increase in long-term risks. [ABSTRACT FROM AUTHOR]

Background: Both post-traumatic stress disorder (PTSD) and insomnia are independently associated with a greater risk of cardiovascular mortality. The objective of this study is to determine whether PTSD plus insomnia is associated with a higher risk of major adverse cardiovascular events (MACEs) than either condition alone in a large cohort of veterans.Methods: We conducted a retrospective analysis of the national Veterans Health Administration (VHA) electronic medical records covering veterans 18 years or older with the diagnosis of PTSD, insomnia, or both from January 1, 2015, to December 31, 2020. MACE was defined as new-onset myocardial infarction (MI), transient ischemic attack (TIA) or stroke, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters.Results: A total of 19,080 veterans, 1840 with PTSD plus insomnia and 17,240 with either PTSD or insomnia, were included in the analysis. Baseline mean (SD) age was 46.3 (11.5) years. During median follow-up of 3.9 (interquartile range, 2.4-5.1) years, 206 (1%) veterans developed incident MACE. Cumulative incidence for MI, TIA and/or stroke was larger in veterans with PTSD plus insomnia compared to PTSD and insomnia alone (p=0.008). In a Cox proportional hazards model, PTSD plus insomnia was significantly associated with greater risk of developing MACEs (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50, p=0.01) than either condition after adjusting for multiple covariates including age, gender, smoking, hypertension, depression, and burden of comorbidities.Conclusions: This cohort study found that PTSD plus insomnia is a risk factor for MACEs of greater magnitude than PTSD- or insomnia-alone. [ABSTRACT FROM AUTHOR]

Background: Examining a variety of diet quality methodologies will inform best practice use of diet quality indices for assessing all-cause and cardiovascular disease (CVD) mortality.Objectives: To examine the association between 3 diet quality indices (Australian Dietary Guideline Index, DGI; Dietary Inflammatory Index, DII; Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay, MIND) and risk of all-cause mortality, CVD mortality, and nonfatal CVD events ≤19 y later.Methods: Data on 10,009 adults (mean age 51.8 y; 52% female) from the Australian Diabetes, Obesity, and Lifestyle study were used. An FFQ was used to calculate DGI, DII, and MIND at baseline. Cox proportional hazard models were used to estimate HRs and 95% CI of all-cause mortality, CVD mortality, and nonfatal CVD events (stroke; myocardial infarction) according to 1 SD increase in diet quality, adjusted for age, sex, education, smoking, physical activity, energy intake, history of stroke or heart attack, and diabetes and hypertension status.Results: Deaths due to all-cause (n = 1955) and CVD (n = 520), and nonfatal CVD events (n = 264) were identified during mean follow-ups of 17.7, 17.4, and 9.6 y, respectively. For all-cause mortality, HRs associated with higher DGI, DII, and MIND were 0.94 (95% CI: 0.89, 0.99), 1.08 (95% CI: 1.02, 1.15), and 0.93 (95% CI: 0.89, 0.98), respectively. For CVD mortality, HRs associated with higher DGI, DII, and MIND were 0.93 (95% CI: 0.85, 0.99), 1.10 (95% CI: 1.00, 1.24), and 0.90 (95% CI: 0.82, 0.98), respectively. There was limited evidence of associations between diet quality and nonfatal CVD events.Conclusions: A better quality diet predicted lower risk of all-cause and CVD mortality in Australian adults, whereas a more inflammatory diet predicted higher mortality risk. These findings highlight the applicability of following Australian dietary guidelines, a Mediterranean-style diet, and a low-inflammatory diet for the reduction of all-cause and CVD mortality risk. [ABSTRACT FROM AUTHOR]

Background: Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH).Objectives: This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH.Methods: From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP).Results: Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group.Conclusions: In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients. [ABSTRACT FROM AUTHOR]

Background: Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH.Methods: We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART.Findings: Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2).Interpretation: The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials.Funding: UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

• Most studies identify pre-stroke impairment of activities of daily living (ADL) as a predictor for post-stroke functional outcome. • These studies however obtain information retrospectively, with inherent risks of selection and recall bias. • We found pre-stroke ADL not to be predictive for outcome after stroke in large prospective study, minimizing selection and recall bias. Pre-stroke impairment of activities of daily living (ADL) is considered a major determinant for functional outcome after stroke. However, findings are based on studies in stroke patients in which pre-stroke information is gathered retrospectively, with inherent risks of selection and recall bias. The objective of this study was to verify the predictive value of pre-stroke ADL with respect to ADL decline in a large prospective cohort of community dwelling older subjects with known vascular risk factors or vascular disease, thereby minimizing selection and recall bias. Within the four-year study follow-up of a cohort including 5,804 community dwelling older subjects from three countries at risk for vascular disease, incident stroke survivors were identified. Incident myocardial infarction (MI) survivors and the remaining study survivors without incident vascular events served as comparison groups. Multivariate logistic regression analyses for each of the aforementioned groups were performed to assess associations between pre-stroke ADL by the Barthel Index (BI) and Instrumental Activities of Daily Living (IADL) scale and risk for ADL decline. In stroke survivors, neither pre-event BI (n = 230, OR 1.00 (95% CI 0.83–1.23)) nor IADL (OR 1.07 (95% CI 0.94 – 1.20)) predicted risk of post-stroke ADL decline in contrast to ADL decline after MI (n = 443, OR 0.83 (95% CI 0.70–0.98) and 0.87 (95% CI 0.78–0.97) respectively) and the group without vascular events (n = 4336, OR 0.85 (95% CI 0.78–0.92) and 0.87 (95% CI 0.83–0.92) respectively). In the present prospective cohort of community dwelling older subjects with known vascular risk factors, pre-stroke ADL measured by BI and IADL scale did not predict post-stroke ADL decline. [ABSTRACT FROM AUTHOR]

Since 2007, the Korean government has provided a free health screening to the elderly starting at the age of 66 years. The purpose of this study was to evaluate the association between this general health screening and the incidences of stroke and myocardial infarction and mortality. The study design used in this study is a retrospective cohort study. The study was conducted using the universe of insurance claims data of Korea and followed a cohort of individuals aged 66 years in 2009 from 2006 through 2016 (n = 354,194). We assessed the association between receipt of the national health screening and health outcomes using propensity matching and Cox proportional hazard models. We found that the receipt of the national health screening was associated with a reduction in negative health outcomes. The hazard ratio for stroke was 0.89 (P < 0.001), 0.88 (P < 0.001) for myocardial infarction and 0.58 for death (P < 0.001). Korea's national health screening was associated with reductions in cardiovascular morbidity and mortality in the elderly. The receipt of the national health screening in the elderly was associated with a reduction in negative health outcomes including stroke, myocardial infarction, and death. Image 1 • Many studies have claimed that health screening has little effect. • This study shows that the national health screening may be helpful for the elderly. • However, the cost-effectiveness can vary from country to country. [ABSTRACT FROM AUTHOR]

Abstract Aims With increasing age, physical inactivity and sedentary behaviour levels increase, as does cardiovascular disease (CVD) incidence. We investigate how device-measured sedentary behaviour and physical activity (PA) are related to CVD onset in men aged 70+; whether the total volume of activity is more important than pattern. Methods and results Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–80. In 2010–12, 3137 survivors were invited to complete questionnaires and wear an Actigraph GT3x accelerometer for 7 days. PA intensity was categorised as sedentary, light and moderate to vigorous (MVPA). Men were followed up for Myocardial Infarction, stroke and heart failure (ICD9 410–414, 430–438 and 428) morbidity and mortality from 2010 to 12 to June 2016. Hazard Ratios (HRs) for incident Cardiovascular Disease (CVD) were estimated. 1528/3137 (49%) men had sufficient accelerometer data. 254 men with pre-existing CVD were excluded. Participants' mean age was 78.4 (range 71–92) years. After median 4.9 years follow-up, 122 first CVD events occurred in 1181 men (22.7/1000 person-years) with complete data. For each additional 30 min in sedentary behaviour, light PA,10 min in MVPA, or 1000 steps/day, HRs for CVD were 1.09(95%CI 1.00, 1.19), 0.94(0.85, 1.04), 0.88(0.81, 0.96) and 0.86(0.78 to 0.95) respectively, adjusted for measurement-related factors, socio-demographics, health behaviours and disability. HRs for accumulating 150 min/week MVPA in bouts ≥1 min and bouts ≥10 min were 0.47(0.32 to 0.69), and 0.49(0.25, 0.98). Conclusions In older men, high volume of steps or MVPA rather than MVPA bouts was associated with reduced CVD risk. Highlights • Prospective studies report that self-reported physical activity protects against cardiovascular disease (CVD). • Yet, self-reported behaviours cannot easily be used to assess the value of the 10 min activity bouts specified in guidelines. • This is the first study of risk of fatal and non-fatal CVD based on device measured physical activity and sedentary behaviour. • Among 1181 men aged over 70 years, more time in moderate to vigorous physical activity and more steps reduced 5-year CVD risk. • The pattern of accumulating moderate to vigorous physical activity in 10 min bouts was not important for CVD risk. [ABSTRACT FROM AUTHOR]

We studied the association between neighborhood socioeconomic status (SES) and incidence of coronary heart disease (CHD) or ischemic stroke in the total population and in full- and half-siblings to determine whether these associations are causal or a result from familial confounding. Data were retrieved from nationwide Swedish registers containing individual clinical data linked to neighborhood of residence. After adjustment for individual SES, the association between neighborhood SES and CHD showed no decrease with increasing genetic resemblance, particularly in women. This indicates that the association between neighborhood SES and CHD incidence is partially causal among women, which represents a novel finding. [ABSTRACT FROM AUTHOR]

Aims: This study describes the incidence and predictive factors for development of Type II Diabetes Mellitus (T2DM), Acute Myocardial Infarction (AMI) and stroke, among subjects with IFG over a five-year period.Methods: This is a retrospective cohort study of subjects with newly diagnosed IFG from the Singapore National Healthcare Group hospitals and primary care clinics from 1 January 2008 to 31 December 2010. Clinical data were collected over a five-year period from the date of diagnosis. Outcomes of interest were T2DM, AMI and stroke based on first occurrence of the ICD-9 diagnoses from the chronic disease registry. Demographic characteristics, laboratory tests, anthropometric measurements and medical history were adjusted for in the multivariate logistic regression.Results: Out of 2295 eligible subjects, 552(24.1%) developed at least one of the outcomes. 492(21.4%) developed T2DM, 20(0.9%) developed AMI and 62(2.7%) developed stroke. Predictive factors for development of any of the three outcomes included age 40-49 [Adjusted OR=2.25; 95% CI 1.44-3.51], blood pressure of 140/90mmHg and above [Adjusted OR=1.62, 95% CI 1.26-2.10] and BMI of 27.5kg/m2 or more [Adjusted OR=2.35; 95% CI 1.61-3.41]. Females were more likely to develop T2DM [Adjusted OR=1.43; 95% CI 1.10-1.85] but less likely to develop AMI and/or stroke compared to males [Adjusted OR=0.43; 95% CI 0.24-0.76].Conclusions: Development of T2DM/AMI/stroke within the first five years of IFG is significantly high for subjects age 40-49 and those with high BMI. Frequency of cardiovascular risk screening, which is currently once every three years, could be increased. [ABSTRACT FROM AUTHOR]

Background: Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available.Objectives: This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation.Methods: We conducted a prospective, single-center cohort study, including 907 patients with AF treated with vitamin K antagonists (3,865 patient-years), to assess CVEs, including fatal and nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At admission, plasma PCSK9 and urinary 11-dh-TxB2 (n = 852) were measured. The population was divided into tertiles of PCSK9 for the analysis.Results: The mean age of patients was 73.5 ± 8.2 years, and 43.0% were women. At follow-up, 179 CVEs (4.6%/year) occurred: 43 (15.3%), 49 (15.5%), and 87 (28.0%) in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009). Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,000 to 2,300 pg/ml] vs. 1,200 pg/ml [IQR: 827 to 1,807 pg/ml], respectively; p < 0.001). Multivariable Cox regression analysis showed that the third versus the first tertile of PCSK9 (hazard ratio: 1.640; 95% confidence interval: 1.117 to 2.407; p = 0.012), female sex, age, diabetes, smoking, heart failure, previous cerebrovascular and cardiac events, digoxin use, and total cholesterol to high-density lipoprotein cholesterol ratio were associated with CVEs. In 682 patients not treated with antiplatelet therapy, circulating PCSK9 and 11-dh-TxB2 were significantly correlated (Spearman's rho: 0.665; p < 0.001).Conclusions: Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism potentially implicated in platelet activation. [ABSTRACT FROM AUTHOR]

Background: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF.Objectives: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF.Methods: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk.Results: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98).Conclusions: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA. [ABSTRACT FROM AUTHOR]

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time.Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.Methods: The PEGASUS-TIMI (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 randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).Results: A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).Conclusions: Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562). [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have increased risk of thromboembolic events such as stroke and myocardial infarction (MI). Although it has been established that the efficacy of anticoagulation is superior to that of antiplatelet agents for stroke prophylaxis in AF, the optimal antithrombotic treatment remains uncertain for primary protection against MI.Objectives: The authors investigated the incidence of first-time MI in patients with AF according to antithrombotic treatment and estimated the risk of stroke and bleeding.Methods: Subjects with first-time AF diagnosed from 1997 to 2012 without history of coronary artery disease were identified using Danish nationwide administrative registries. Subjects were divided into time varying exposure groups according to antithrombotic treatment. The relative risks of outcomes were estimated by Poisson regression models.Results: A total of 71,959 patients (median 75 years of age; females: 47%). At baseline, 37,539 patients (52%) were treated with vitamin K antagonist (VKA) monotherapy, 25,458 (35%) with acetylsalicylic acid (ASA) monotherapy and 8,962 (13%) with dual-therapy (VKA + ASA). The incidence of MI was 3% (n = 2,275). Relative to the VKA-treated group, the associated risk of MI was significantly higher for ASA (incidence rate ratio [IRR]: 1.54; 95% confidence interval [CI]: 1.40 to 1.68) and dual-therapy (IRR: 1.22; 95% CI: 1.06 to 1.40). The bleeding risk was significantly higher for dual-therapy (IRR: 1.93; 95% CI: 1.81 to 2.07). The risk of stroke relative to that of VKA therapy was significantly higher for both ASA (IRR: 2.00; 95% CI: 1.88 to 2.12) and dual-therapy (IRR: 1.30; 95% CI: 1.18 to 1.43).Conclusions: VKA monotherapy in patients with AF was associated with a lower risk of first-time MI and stroke than ASA monotherapy. Combination of ASA and VKA therapy was not associated with a lower risk of MI but was associated with increased bleeding risk. [ABSTRACT FROM AUTHOR]

Background Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects. Our aim was to evaluate whether CV risk differs by type of ADT. Methods Through nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (gonadotrophin releasing hormone [GnRH] agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July, 2010, and the 31st December, 2011, and followed them up to 31st December, 2013. The main analysis followed an ‘on-treatment’ approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HRs) for hospitalisations for ischaemic events (myocardial infarction or ischaemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk. Results Among the 35,118 new ADT users, 71% received GnRH agonist (reference group), 12% CAB, 13% AA, 3.6% GnRH antagonist and 0.6% had OT. CAB was associated with an increased risk (adjusted HR [95% confidence interval {CI}], 1.6 [1.3–2.0]) and AA with a decreased risk (adjusted HR [95% CI], 0.6 [0.4–0.9]) of ischaemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95% CI], 1.2 (0.7–2.1)). Conclusion CV risk appeared different across ADT modalities. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. In a context where better overall and cancer specific survival without worsening quality of life is a challenge for clinicians, a potential heterogeneity in CV morbidity becomes crucial when choosing an ADT. [ABSTRACT FROM AUTHOR]

Objective: Women with diabetes have a greater excess risk for cardiovascular diseases (CVD) than men. This study was aimed at clarifying whether this effect is lifelong or more evident in some life-periods.Methods: The effect of diabetes and gender on the risk of first ever hospitalization for acute myocardial infarction (AMI), ischemic stroke (IS), congestive heart failure (CHF), lower extremity amputations (LEA) or any of these major cardiovascular events (MACE) have been evaluated by a Cox-hazard model, over years 2008-2012 querying administrative databases of a cohort living in Tuscany, Italy.Results: Comparing subjects with diabetes to those without it the overall age-adjusted excess risk was higher in women than in men for AMI and MACE and higher in men for LEA, with no difference for IS or CHF. In women the excess risk for AMI and MACE started earlier (46yr) and lasted until age of more than 85yr, while 'risk-windows' opened later and had a shorter duration for CHF (56-65yr) and IS (66-75yr).Conclusion: Diabetic women have a significant diabetes-associated excess of CVD risk, except for LEA, with a 'risk window' opening earlier and lasting longer for AMI and MACE, later and with a shorter duration for IS and CHF. [ABSTRACT FROM AUTHOR]

Background: It is unknown how risk of myocardial infarction and stroke differ for patients with and without anxiety or depression, and whether this risk can be explained by demographics, medication use, cardiovascular risk factors. The aim of this study is to quantify differences in risk of non-fatal MI or stroke among patients with anxiety or depression.Methods: Prospective cohort study examining risk of incident MI and stroke between March 2005 and March 2015 for 524,952 patients aged 30 and over from the east London primary care database for patients with anxiety or depression.Results: Amongst 21,811 individuals with depression at baseline, 1.2% had MI and 0.4% had stroke. Of 22,128 individuals with anxiety at baseline, 1.1% had MI and 0.3% had stroke. Depression was independently associated with both MI and stroke, whereas anxiety was associated with MI only before adjustment for cardiovascular risk factors. Antidepressant use increased risk for MI but not stroke. Mean age at first MI was lower in those with anxiety, while mean age at first stroke was lower in those with depression.Limitations: The study was limited to patients currently registered in the database and thus we did not have any patients that died during the course of follow-up.Conclusions: Patients with depression have increased risk of cardiovascular events. The finding of no increased cardiovascular risk in those with anxiety after adjusting for cardiovascular risk factors is of clinical importance and highlights that the adequate control of traditional risk factors is the cornerstone of cardiovascular disease prevention. Targeting management of classical cardiovascular risk factors and evaluating the risks of antidepressant prescribing should be prioritized. [ABSTRACT FROM AUTHOR]

Background: Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor.Objectives: The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients.Methods: We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files.Results: Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio [HR]: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups.Conclusions: Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Although multivitamins are widely used by US adults, few prospective studies have investigated their association with the long- and short-term risks of cardiovascular disease (CVD).Objective: The aim of this study was to investigate how multivitamin use is associated with the risk of CVD in initially healthy men at baseline.Methods: We studied 18,530 male physicians aged ≥40 y from the Physicians' Health Study I cohort who were free of CVD and cancer at baseline (1982). All men provided a wide range of self-reported lifestyle and clinical factors plus intake of selected foods and dietary supplements. Cox proportional hazards models were used to calculate multivariable-adjusted HRs (95% CIs).Results: During a mean follow-up of 12.2 y (total of 225,287 person-years), there were 1697 incident cases of major CVD (defined as nonfatal myocardial infarction, nonfatal stroke, and CVD death). In multivariable-adjusted analyses, no significant associations were observed among baseline multivitamin users compared with nonusers for the risk of major CVD events (HR: 0.94; 95% CI: 0.84, 1.05), whereas a self-reported duration of ≥20 y at baseline was associated with lower risk (HR: 0.56; 95% CI: 0.35, 0.90; P-trend = 0.05). Baseline multivitamin use was also significantly inversely associated with the risk of cardiac revascularization (HR: 0.86; 95% CI: 0.75, 0.98). Baseline use of multivitamins was not significantly associated with other CVD endpoints.Conclusion: In this long-term prospective study in initially healthy men, multivitamin use for ≥20 y was associated with a lower risk of major CVD events. [ABSTRACT FROM AUTHOR]

Objective: To assess hard major adverse clinical events (HMACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Background: There are limited data regarding long-term HMACE risks based on PCI-CTO success.Methods: First-time PCI was performed in 438 consecutive patients with 473 target CTO lesions. Patients after procedural success (n=355; 378 CTO lesions) and failure (n=83; 95 CTO lesions) were followed for an average 40months (7-77months range). We compared HMACE (composite of cardiac death, non-fatal myocardial infarction (MI), and stroke) dependent on the success of PCI.Results: The incidence of HMACE was low, with a total of 16 events, and did not differ {6% vs.3.1%, HR=0.47; CI [0.16-1.35; p=0.162} dependent on the success of PCI-CTO. There were less cardiac deaths {0.3% vs. 1.2%, RR=0.22; CI [0.01-3.50];p=0.283}, non fatal MI {1.1% vs.3.6%, RR=0.27; CI [0.06-1.22], p=0.089}, but more strokes {1.7% vs.1.2%, RR=1.32; CI [0.16-10.99], p=0.795} after successful PCI-CTO.Conclusions: The risks of HMACE after PCI-CTO over long-term follow-up were minimal, and do not depend on the procedure success. This unexpected finding somewhat challenge the aggressive interventional approach, and should be confirmed in the adequately powered randomized trial. [ABSTRACT FROM AUTHOR]

Background: With increasing longevity and a similar or increased prevalence of cardiovascular disease risk factors (as compared to the general population), people with intellectual disabilities (IDs) are at risk of developing cardiovascular disease. However, prospective studies on incidence and influencing factors of cardiovascular disease and mortality are lacking.Methods: A three year follow-up study was undertaken to study the incidence and symptoms at presentation of myocardial accident, stroke and heart failure in older people with ID. Furthermore, the predictive value of cardiovascular disease risk factors on myocardial accident, stroke and heart failure and on all-cause mortality were studied. The baseline group consisted of the 1050 participants, aged 50 years and over, in the Dutch Healthy Ageing and Intellectual Disability (HA-ID) study. Baseline measurements were conducted between November 2008 and July 2010. Three years after baseline, medical files of 790 participants were studied.Results: Cardiovascular disease (myocardial infarction, stroke and heart failure) occurred in 5.9% of the population during 3 year follow-up, and 32% of them died due to the condition. Incidence of myocardial infarction is 2.8 per 1000 personyears, for stroke 3.2 per 1000 personyears and for heart failure 12.5 per 1000 personyears. Incidence of these conditions is probably underestimated, due to atypical symptom presentation. The use of atypical antipsychotics and a history of heart failure were predictive for myocardial infarction. Heart failure was predicted by abdominal obesity, chronic kidney disease and a history of heart failure. A total of cardiovascular disease (myocardial infarction, stroke or heart failure) was predicted by abdominal obesity, a history of stroke and a history of heart failure. A low body-mass index, peripheral arterial disease, chronic kidney disease and inflammation were predictive for 3-year all-cause mortality.Conclusion: Incidence of cardiovascular disease in older people with ID is similar to that in the general population. A pro-active assessment and treatment of the presented cardiovascular disease risk factors may reduce cardiovascular disease and mortality in older people with ID. [ABSTRACT FROM AUTHOR]

Background: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.Objectives: This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).Methods: CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).Results: The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).Conclusions: CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker. [ABSTRACT FROM AUTHOR]

Background: The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood.Objectives: The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care.Methods: The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus.Results: Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64).Conclusions: In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups. [ABSTRACT FROM AUTHOR]

Background: There is no consensus whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) should be used for secondary prevention in all or in only high-risk patients after an acute myocardial infarction (AMI).Objectives: This study sought to investigate whether ACEI/ARB treatment after AMI is associated with better outcomes across different risk profiles, including the entire spectrum of estimated glomerular filtration rates.Methods: This study evaluated discharge and continuous follow-up data on ACEI/ARB use among AMI survivors (2006 to 2009) included in a large Swedish registry. The association between ACEI/ARB treatment and outcomes (mortality, myocardial infarction, stroke, and acute kidney injury [AKI]) was studied using Cox proportional hazards models (intention-to-treat and as treated).Results: In total, 45,697 patients (71%) were treated with ACEI/ARB. The 3-year mortality was 19.8% (17.4% of ACEI/ARB users and 25.4% of nonusers). In adjusted analysis, significantly better survival was observed for patients treated with ACEI/ARB (3-year hazard ratio: 0.80; 95% confidence interval: 0.77 to 0.83). The survival benefit was consistent through all kidney function strata, including dialysis patients. Overall, those treated with ACEI/ARB also had lower 3-year risk for myocardial infarction (hazard ratio: 0.91; 95% confidence interval: 0.87 to 0.95), whereas treatment had no significant effect on stroke risk. The crude risk for AKI was in general low (2.5% and 2.0% for treated and nontreated, respectively) and similar across estimated glomerular filtration rate categories but was significantly higher with ACEI/ARB treatment. However, the composite outcome of AKI and mortality favored ACEI/ARB treatment.Conclusions: Treatment with ACEI/ARB after AMI was associated with improved long-term survival, regardless of underlying renal function, and was accompanied by low rates of adverse renal events. [ABSTRACT FROM AUTHOR]

Background: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin.Objectives: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets.Methods: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists.Results: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group.Conclusions: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921). [ABSTRACT FROM AUTHOR]

Objectives: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder.Method: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders.Results: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46).Limitations: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses.Conclusion: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI).Objectives: The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients.Methods: An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths.Results: In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores.Conclusions: During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972). [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the individual and combined associations of depression and low socioeconomic status (SES) with risk of major cardiovascular events (MCVE), defined as first-ever fatal or non-fatal stroke or myocardial infarction, in a large prospective cohort study.Methods: We used data from 466,238 UK Biobank participants, aged 40-69 years without cardiovascular disease, bipolar disorder or schizophrenia at baseline. We performed Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the individual and combined associations of depression and each of educational attainment, area-based deprivation and income with risk of MCVE. We assessed effect modification and explored interaction on the additive and multiplicative scale.Results: Depression, low education, high area-based deprivation and low income were individually associated with increased risks of MCVE (adjusted HR, 95% CI: 1.28, 1.19-1.38; 1.20, 1.14-1.27; 1.17, 1.11-1.23; and 1.22, 1.16-1.29, respectively). Depression was associated with increased risks of MCVE among individuals with high and low SES. Individuals with depression and each of low education, high area-based deprivation and low income were at particularly high risk of MCVE (HR, 95% CI: 1.50, 1.38-1.63; 1.63, 1.46-1.82; 1.31, 1.23-1.40, respectively). There was interaction between depression and area-based deprivation on multiplicative and additive scales but no interaction with education or income.Conclusion: Depression was associated with increased risks of MCVE among individuals with high and low SES, with particularly high risks among those living in areas of high deprivation. [ABSTRACT FROM AUTHOR]

Background: Research on cannabis-related health outcomes in diverse older adults is limited. The current study utilized a matched cohort study design to compare older adults in Hawai'i with identified cannabis diagnoses and matched controls on chronic health conditions, acute health events, and healthcare utilization from 2016 to 2020.Method: Patients age 50 + were identified using ICD-10 diagnostic codes for cannabis use, abuse, and dependence using electronic health record data from an integrated health system (Kaiser Permanente Hawai'i). Those with cannabis diagnoses (n = 275) were compared to matched non-using controls (n = 275; based on age, sex) on chronic health conditions (coronary heart disease, hypertension, COPD, chronic non-cancer pain), acute health events (myocardial infarction, respiratory symptoms, stroke, persistent or cyclic vomiting, injuries), and healthcare utilization (outpatient, inpatient, and emergency department visits) following case identification for two years.Results: Participants were 19.3% Native Hawaiian/Pacific Islander, 24.4% Asian, 47.8% White, and 8.5% Other/Unknown, with an average age of 62.8 years (SD=7.3). Adjusting for covariates as possible, participants with a cannabis diagnosis had significantly greater risk of coronary heart disease, chronic non-cancer pain, stroke, myocardial infarction, cyclic vomiting, and injuries, over time, compared to controls. Cannabis use was associated with any and greater frequency of outpatient, inpatient, and emergency department visits.Conclusions: In a diverse sample, older adults who used cannabis had worse health conditions and events and used more health services over a two-year period. Future studies should evaluate cannabis-related health outcomes, effects of cannabis problem severity, as well as implications for healthcare in aging populations. [ABSTRACT FROM AUTHOR]

Background: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion.Methods: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732.Findings: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42).Interpretation: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation.Funding: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions. [ABSTRACT FROM AUTHOR]

Abstract: Background and methods: There is controversy about the association between mild-to-moderate alcohol consumption and a reduced risk of cardiovascular diseases. The relationships between daily alcohol consumption and the incidence of acute myocardial infarction (MI) or ischemic stroke (IS) were examined in men in a community-based, prospective cohort study (n = 8014, age 40–80 years, mean age = 64.1 years). Alcohol consumption was categorized into 3 groups (A1, none or occasional; A2, ≤25 g/day; A3, >25 g/day as ethanol) at baseline. Results: During the mean follow-up of 5.5 years, 53 MIs and 186 ISs occurred. On Cox regression analysis adjusted for age, hypertension, diabetes, dyslipidemia, smoking index, and body mass index (BMI), the hazard ratio (HR) for incident MI was significantly lower in the A2 group than in the A1 group (HR = 0.49, p = 0.043). The HR for incident MI in the A3 group tended to be lower than in the A1 group (HR = 0.53, p = 0.10). In obese subjects, while a significantly lower HR for incident MI in the A2 group was retained (HR = 0.29, p = 0.049), no significant difference in the HR of the A3 group compared with the A1 group was found. No significant differences were found in the IS-free curve among the 3 groups of alcohol consumption. Conclusions: Alcohol consumption may have a protective effect on the onset of MI but not on IS in the general population. A U-shaped relation between alcohol consumption and incident MI was found in obese subjects. An appropriate limit for daily alcohol consumption, depending on the risk of ischemic heart disease, may need to be established. [Copyright &y& Elsevier]

Abstract: Background: Recommended fluid intake is regarded as an important factor for stroke prevention. In mass media, drinking of at least 2000ml water per day is recommended for any condition. However, no prospective trials are available which examined the impact of the amount of daily fluid intake on primary stroke prevention or on stroke recurrence. We performed a prospective study evaluating the daily fluid intake over a period of two years in stroke patients. Methods: Patients (n=465) with a complete stroke (i.e., proven ischaemic cerebral infarction) were followed for two years with a regular visit every three months. At every visit the average daily amount of fluid intake was evaluated by a drinking diary. Patients had to protocol all kinds of fluid they were drinking during the day for a whole week. They were divided into two groups: daily intake of more and of less than 2000ml. The rate of primary endpoint (stroke including transient ischaemic attack, myocardial infarction, or death from any cause) and of secondary endpoint (stroke) was calculated for the two groups. In addition, haemorheological parameters such as platelet reactivity, erythrocyte aggregation, and osmolarity were measured at every visit. Results: The mean observation period was 17months. In this period, the patients with recommended fluid intake (mean amount 2427ml) had a primary event rate of 12.3% whereas the patients with the low fluid intake (mean amount 1625ml) had a primary event rate of 16.8%. The Kaplan–Meier analysis revealed a significantly better outcome of the patient group with recommended fluid intake with respect to the primary endpoint (p<0.013) and to the secondary endpoint (p<0.007). We observed a lower platelet reactivity in the patient group with recommended fluid intake as the only significant haemorheological factor influenced by the fluid intake. We observed no association between the amount of fluid intake and conventional vascular risk factors except a higher fluid intake in smokers. Conclusions: Our data suggests that a fluid intake of more than 2000ml per day might by a protective factor in secondary stroke prevention. A recommended fluid intake is associated with a lower platelet reactivity. No other haemorheological parameters were affected by the amount of fluid intake. However, advising patients after stroke on how much fluid they should drink is also influenced by other factors such as renal and cardiac function. [Copyright &y& Elsevier]

Abstract: Background: We recently demonstrated an immediate immunodepressive state after acute ischemic stroke in humans. Methods: In the present study, we prospectively analyzed immune responses in patients with middle cerebral artery stroke (n =20), acute myocardial infarction (n =20) and healthy controls (n =20, also matched for age and gender). Results: Compared to controls, a rapid depression of monocytic HLA-DR expression and a defective lymphocytic IFN-γ production was obvious after ischemic stroke or myocardial infarction, while total counts of leukocytes and monocytes were significantly higher after myocardial infarction. A T cell-mediated lymphopenia was accentuated in patients with severe stroke, obviously predisposing these patients for nosocomial infections. Conclusions: Our data reveal an immediate and to some extent differential suppression of cell-mediated immune responses after ischemic stroke or myocardial infarction respectively. [Copyright &y& Elsevier]

Abstract: Objectives: The endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. Methods: Baseline serum MMP-9 was measured in incident MI (n =368) and stroke (n =299) cases and two controls per case, ‘nested’ in prospective studies of 4252 men and 4286 women aged 60–79 years, sampled from General Practices in Britain in 1998–2000, with 7-year follow-up for fatal and non-fatal MI and stroke. Results: Geometric mean MMP-9 was 528ng/mL (IQR 397, 743) in MI cases compared to 501ng/mL (IQR 370, 743) in controls, p =0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p =0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p =0.045; however adjustments similarly attenuated the associations. Conclusions: While serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either. [Copyright &y& Elsevier]

Objective: In contrast to prior observational studies, hormone replacement therapy (HRT) did not prevent coronary heart disease in the Women's Health Initiative Randomized Controlled Trial (WHI RCT). To assess the validity of a novel observational study design, we compared the WHI RCT with a simulation using data from the United Kingdom General Practice Research Database (GPRD). Study Design and Setting: A cohort from GPRD was used to simulate the WHI RCT by replicating, to the extent possible, all aspects of the RCT except randomization. The study included 37,730 Unexposed and 13,658 Exposed women treated with estrogen and norgestrel. Results: Myocardial infarction (adjusted hazard ratio 0.95 [0.78-1.16]) was not decreased significantly in the GPRD Exposed group. Similar to the WHI RCT, stroke, venous thromboembolic events, and breast cancer were increased; and colorectal cancer was decreased. Although death appeared to decrease in the total cohort, it was unaltered in a subset of subjects without missing data on baseline covariates. Conclusion: A structured comparison using data from GPRD was largely concordant with the WHI RCT and did not show a cardioprotective effect of HRT. These findings further generalize the results of WHI and reinforce the potential utility of this analytic approach. [ABSTRACT FROM AUTHOR]

• Motoric Cognitive Risk Syndrome (MCR), which is a pre-dementia stage. • MCR has been associated with incident Vascular Dementia and Alzheimer Disease. • MCR is associated with cardiovascular diseases and risk factors in both younger and older Canadian individuals. Motoric Cognitive Risk Syndrome (MCR) is a pre-dementia syndrome. The aim of this study was to examine whether there is: 1) an association between MCR and cardiovascular diseases and risk factors (CVDRF) in the Canadian population, and 2) a specific MCR-related CVDRF profile (i.e., cardiovascular diseases (CVD) versus cardiovascular risk factors (CVRF) versus both) when comparing different age groups. A total of 29,569 participants free of dementia were recruited in the Canadian Longitudinal Study on Aging. Participants were categorized into groups by their age and MCR status (with MCR versus without MCR). Overweight/obese, smoking, waist to hip circumference ratio (WHCR), systolic blood pressure and diastolic blood pressure levels were CVRF. Diabetes type I and II, hypertension, heart disease and attack, peripheral vascular disease, angina, stroke and rhythmic disease were CVD. A higher prevalence of CVRF in MCR was shown in the youngest age groups (i.e., 45–54 and 55–64) compared to the other age groups. MCR was positively associated with CVDRF, except in the oldest age group (i.e., ≥75). In this group, the only significant association with CVRF was with diastolic blood pressure, which was negatively associated with MCR. Diabetes and hypertension were not associated with MCR. MCR is associated with CVDRF in both younger and older individuals. A stronger association was present for CVRF factors in younger adults and for CVD in older adults. [ABSTRACT FROM AUTHOR]