Risk Of Subsequent Cardiovascular Events Research Articles

Comparison of Risk of Serious Cardiovascular Events after Hemorrhagic versus Ischemic Stroke: A Population-Based Study

Patients with ischemic stroke are considered a very high risk population for subsequent cardiovascular events and guidelines recommend intensive preventive strategies. However, there is no clear recommendation that patients with hemorrhagic stroke should also be regarded as a very high cardiovascular risk population. To compare the risk of subsequent cardiovascular morbidity/mortality between patients with incident hemorrhagic and ischemic stroke. Patients aged ≥18 years with incident hemorrhagic or ischemic stroke between 1998 and 2017 and no prior history of serious vascular event were identified from UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics data. The cohort included 32,091 patients with an overall follow-up of 381,237 person-years (median: 11.8 years). After adjusting for potential confounders, patients with incident hemorrhagic stroke had no significantly different risk of subsequent cardiovascular morbidity compared with patients with incident ischemic stroke-coronary heart disease (CHD; hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.32), recurrent stroke (HR: 0.92, 95% CI: 0.83-1.02), peripheral vascular disease (PVD; HR: 1.15, 95% CI:0.56-2.38), or heart failure (HR: 1.03, 95% CI: 0.61-1.74). Patients with incident hemorrhagic stroke had significantly higher risk of subsequent cardiovascular disease (CVD)-related mortality (HR: 2.35, 95% CI: 2.04-2.72) and all-cause mortality (HR: 2.16, 95% CI: 1.94-2.41). Propensity-score matched analysis of 1,039 patients with hemorrhagic stroke and 1,039 with ischemic stroke showed similar risk in subsequent cardiovascular morbidity-CHD (stratified HR [sHR]: 0.92, 95% CI: 0.55-1.54), recurrent stroke (sHR: 0.93, 95% CI: 0.82-1.02), PVD (sHR: 1.04 95% CI: 0.45-2.41), or heart failure (sHR: 0.71, 95% CI: 0.39-1.27). The risk of subsequent cardiovascular events is similar between patients with incident hemorrhagic and ischemic stroke. Patients with previous hemorrhagic stroke should be regarded as a population at very high risk for subsequent CVD.

Coronavirus Disease 2019 Severity and Risk of Subsequent Cardiovascular Events.

Little is known about the relationship between coronavirus disease 2019 (COVID-19) severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of United States adults. Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between 1 April 2020 and 31 May 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 days after COVID-19 diagnosis using inverse probability of treatment-weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only. A total of 1 357 518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [aHR], 1.80 [95% confidence interval {CI}, 1.71-1.89]) or non-ICU hospitalization (aHR, 1.28 [95% CI, 1.24-1.33]). Risk of subsequent hospitalization for CVE was even higher (aHRs, 3.47 [95% CI, 3.20-3.76] for ICU and 1.96 [95% CI, 1.85-2.09] for non-ICU hospitalized vs outpatient only). COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder COVID-19 who were managed solely in the outpatient setting, even after adjusting for differences between these groups. These findings underscore the continued importance of preventing severe acute respiratory syndrome coronavirus 2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.

Lipid lowering therapy patterns and the risk of cardiovascular events in the 1-year after acute myocardial infarction in United Arab Emirates.

AimIn United Arab Emirates, cardiovascular disease (CVD) is a leading cause of mortality and 22% of CVD deaths are attributable to acute myocardial infarction (MI). Adherence to guidelines for lipid management is incompletely described in the Middle East. This study aimed to characterize lipid lowering therapy (LLT) patterns and the risk of subsequent cardiovascular events (CVEs) in the first year after MI.MethodsThis was a retrospective cohort study using the Dubai Real-World Claims Database, including all patients discharged with MI between January 01, 2015 and December 31, 2018, followed-up until December 31, 2019.ResultsIn the first year after MI, 8.42% of 4,595 patients included experienced at least one recurrent MI (rate 6.77 events/100 person-years [PYs]), 2.94% had one revascularization (cumulative rate 0.55 events/100 PYs) and 2.66% had one hospitalization due to unstable angina (cumulative rate 5.16 new events/100 PYs). The majority (60.40%) of the patients presented with LDL-C levels ≥ 70 mg/dL after MI. In the first year after MI, 93.45% of the patients received LLT, mainly high-intensity statin (67.79%); with a minority of patients receiving statin + ezetimibe (4.55%), PCSK9i (0.20%) or ezetimibe alone (0.07%).ConclusionPatients hospitalized with MI in Dubai present an increased risk of CVEs in their first-year post-discharge. Majority of the patients presented with LDL-C levels above 70 mg/dL, which indicates suboptimal lipid control with existing LLT, particularly in high-risk patients.

Physical Function and Subsequent Risk of Cardiovascular Events in Older Adults: The Atherosclerosis Risk in Communities Study.

BackgroundReduced physical function, a representative phenotype of aging, has been associated with cardiovascular disease (CVD). However, few studies have comprehensively investigated its association with composite and individual CVD outcomes in community‐dwelling older adults and its predictive value for CVD beyond traditional risk factors.Methods and ResultsWe studied 5570 participants (mean age 75 [SD 5] years, female 58%, Black 22%) at visit 5 (2011–2013) of the ARIC (Atherosclerosis Risk in Communities) study. Physical function was evaluated with the Short Physical Performance Battery (SPPB), which incorporates a walk test, chair stands, and balance tests. The SPPB score was modeled categorically (low [0–6], intermediate [7–9], and high [10–12]) and continuously. We assessed the associations of SPPB score with subsequent composite (coronary heart disease, stroke, or heart failure) and individual CVD outcomes (components within composite outcome) using multivariable Cox models adjusting for major CVD risk factors and history of CVD. We also evaluated improvement in C‐statistics by adding SPPB to traditional CVD risk factors in the Pooled Cohort Equation. Among the study participants, 13% had low, 30% intermediate, and 57% high SPPB scores. During a median follow‐up of 7.0 (interquartile interval 5.3–7.8) years, there were 930 composite CVD events (386 coronary heart disease, 251 stroke, and 529 heart failure cases). The hazard ratios of composite CVD in low and intermediate versus high SPPB score were 1.47 (95% CI, 1.20–1.79) and 1.25 (95% CI, 1.07–1.46), respectively, after adjusting for potential confounders. Continuous SPPB score demonstrated independent associations with each CVD outcome. The associations were largely consistent across subgroups (including participants with prevalent CVD at baseline). The addition of SPPB to traditional CVD risk factors significantly improved the C‐statistics of CVD outcomes (eg, ΔC‐statistic 0.019 [95% CI, 0.011–0.027] for composite CVD).ConclusionsReduced physical function was independently associated with the risk of composite and individual CVD outcomes and improved their risk prediction beyond traditional risk factors in community‐dwelling older adults. Although confirmatory studies are needed, our results suggest the potential usefulness of SPPB for classifying CVD risk in older adults.

The position of renal denervation in treatment of hypertension: an expert consensus statement.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as anon-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate anew, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration).

Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality.

People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person’s degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic disease later in life; we pooled data from two population-based Swedish prospective cohort studies (n = 53,507), and we contrasted an individual’s cardiometabolic biomarker profile with the profile predicted for them given their lifestyle exposure characteristics using a quantile random forest approach. People who were classed as ‘sensitive’ to hypertension- and dyslipidemia-related lifestyle exposures were at higher risk of developing cardiovascular disease (CVD, hazards ratio 1.6 (95% CI: 1.3, 1.91)), compared with the general population. No differences were observed for type 2 diabetes (T2D) risk. Here, we report a novel approach to identify individuals who are especially sensitive to adverse lifestyle exposures and who are at higher risk of subsequent cardiovascular events. Early preventive interventions may be needed in this subgroup.

Assessment of the burden of disease for patients with peripheral artery disease undergoing revascularization in England.

Background: Symptoms, severity, and acuteness of peripheral artery disease (PAD) are major determinants of severe limb symptoms, subsequent risk of cardiovascular events, and mortality. Lower-extremity revascularization (LER) is a key option to relieve symptoms and to prevent limb loss in symptomatic patients with PAD. This study aimed to quantify the burden of disease among patients with PAD-LER in England. Methods: A retrospective population-based study of linked primary and secondary care electronic health records, included 13,869 adult patients (aged ⩾ 18 years) with PAD-LER from 2003 to 2018. The incidence of first ever PAD-LER was estimated both overall and by type of procedure (endovascular/surgical). Health resource utilization associated with PAD-related complications and treatment patterns were assessed. Results: A high annual incidence of lower-limb revascularization (41.2 per 1000 person years) and a nearly double incidence of endovascular first revascularization compared with open surgery were observed. More than 70% of patients with PAD-LER had a history of hyperlipidemia and hypertension and roughly one-third were diabetic and had a history of coronary artery disease. Cardiovascular mortality accounted for one-third (34.1 per 1000 person years) of all-cause mortality. Over 93% of patients were hospitalized for any reason and the commonest reasons for hospitalization were cardiovascular diseases and PAD with about one-third hospitalized for revascularization reoccurrence. Conclusion: There is a significant burden of PAD-LER to the individual and society with ongoing healthcare resource utilization, treatment, and increasing mortality.

749-P: Clinically Relevant Predictors of Cardiovascular Events: Exploratory Analysis from the VERIFY Study of Initial Treatment of Type 2 Diabetes Mellitus

The VERIFY study of primary treatment in type 2 diabetes mellitus (T2DM) , showed delayed glycemic failure (HbA1c ≥7.0% at two consecutive scheduled visits post randomization) with early combination of vildagliptin and metformin (EC) versus initial metformin monotherapy in patients with newly diagnosed T2DM (HbA1c 6.5%-7.5%) . Throughout the 5-year study, 57 adjudicated cardiovascular (CV) events were collected but the study was not powered to test the hypothesis that EC was also able to decrease CV events. Here we explore whether simple clinical data at T2DM onset (Framingham risk equation, CV disease history [CVD-Hx]) could identify patients at risk of subsequent CV events. At baseline, Framingham risk score (FRS) was 14.9±9.2% and 220 (12.3%) patients had CVD-Hx. A significant higher risk in patients with CVD-Hx and FRS ≥20% was visually apparent on KM curves and log rank-test (p=0.001; Figure) . Baseline HbA1c, age and gender were not significantly associated with the CV outcome, whereas treatment failure within the first 3 years was significantly associated with a higher risk of CV events (HR [95% CI]: 3.1 [1.7, 5.6]; p=0.0001) . These analyses suggests that both CV risk stratification at onset of T2DM and early loss of glycemic control may identify patients at higher risk of subsequent CV events. Disclosure D.R.Matthews: Advisory Panel; Novo Nordisk A/S, Other Relationship; Novartis AG, Speaker's Bureau; Servier Laboratories. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. P.M.Paldanius: Consultant; Glyconics Ltd, UPM Biomedicals, Speaker's Bureau; Novartis AG, UPM Biomedicals. G.Bader: Employee; Novartis AG. Funding Novartis

748-P: Clinically Relevant Predictors of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from Clinical Studies

Patients with type 2 diabetes mellitus (T2DM) are at greater risk of developing cardiovascular disease (CVD) . We aimed to explore the association between several baseline parameters and risk of cardiovascular (CV) events in patients with T2DM and whether evidence from clinical data at T2DM onset could be useful in identifying patients at risk of subsequent CV events. Data for baseline visits were extracted from 34 globally conducted clinical studies. Framingham risk equation was used to assess the CV risk at baseline. In the overall pooled population (n=18,076) , 2130 (13.6%) patients had CVD history at baseline. The mean (SD) age of the patients was 56.8 (10.7) years, total cholesterol was 196.4 (41.0) mg/dL, low-density lipoprotein (LDL) was 115.4 (36.8) mg/dL, systolic blood pressure (SBP) was 132.7 (14.6) mmHg with disease duration of 5. (5.10) years and Framingham risk score (FRS) of 20.71 (12.68) . An incremental risk for subsequent CV events was observed in patients having none or multiple risk factors. Patients having CVD history and FRS ≥20% were significantly associated with a higher risk of CV events (HR [95% CI]: 7.8 [5.0, 12.3]; p<0.001; Figure) . Overall, these analyses suggests that clinical data collected at the onset and follow-up of T2DM such as CVD history, high LDL and SBP may help in identifying patients who are at high risk of subsequent CV events. Disclosure A.Malhotra:Employee; Novartis India . G.Bader:Employee; Novartis AG. Funding Novartis Pharma AG

Lipid Testing Trends Before and After Hospitalization for Myocardial Infarction Among Adults in the United States, 2008-2019.

BackgroundRoutine monitoring of low-density lipoprotein cholesterol (LDL-C) identifies patients who may benefit from modifying lipid-lowering therapies (LLT). However, the extent to which LDL-C testing is occurring in clinical practice is unclear, specifically among patients hospitalized for a myocardial infarction (MI).MethodsUsing US commercial claims data, we identified patients with an incident MI hospitalization between 01/01/2008-03/31/2019. LDL-C testing was assessed in the year before admission (pre-MI) and the year after discharge (post-MI). Changes in LDL-C testing were evaluated using a Poisson model fit to pre-MI rates and extrapolated to the post-MI period. We predicted LDL-C testing rates if no MI had occurred (ie, based on pre-MI trends) and estimated rate differences and ratios (contrasting observed vs predicted rates).ResultsOverall, 389,367 patients were hospitalized for their first MI during the study period. In the month following discharge, 9% received LDL-C testing, increasing to 27% at 3 months and 52% at 12 months. Mean rates (tests per 1000 patients per month) in the pre- and post-MI periods were 51.9 (95% CI: 51.7, 52.1) and 84.4 (95% CI: 84.1, 84.6), respectively. Over 12 months post-MI, observed rates were higher than predicted rates; the maximum rate difference was 66 tests per 1000 patients in month 2 (rate ratio 2.2), stabilizing at a difference of 15–20 (ratio 1.2–1.3) for months 6–12.ConclusionAlthough LDL-C testing increased following MI hospitalization, rates remained lower than recommended by clinical guidelines. This highlights a potential gap in care, where increased LDL-C testing after MI may provide opportunities for LLT modification and decrease risk of subsequent cardiovascular events.

Cost-benefit analysis of new lipid-lowering agents

Patients with atherosclerotic cardiovascular disease have ahigh risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents acentral and direct cause of this, with afrequent failure to achieve the target values recommended in the guidelines. New lipid-lowering substances are increasingly becoming available for treatment of this residual risk. Due to their high cost, cost-effectiveness analyses are required in order to justify their use. Important variables when considering the cost-effectiveness of adrug are quality adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). The lower bounds of the ICER determining the cost-effectiveness of atreatment vary between healthcare systems. The proprotein convertase subtilisin-kexin type9 (PCSK9) inhibitors alirocumab and evolocumab are deemed to be cost-effective particularly in patients with high levels of low-density lipoprotein cholesterol (LDL-C) prior to treatment or with ahigh cardiovascular risk as determined by the presence of defined risk criteria. Similar considerations apply to the PCSK9 small interfering RNA (siRNA) inclisiran. Administration of bempedoic acid is deemed cost-effective especially in patients with statin intolerance. Eicosapentaenoic acid is deemed cost-effective overall, although the data with respect to the exact placebo-controlled efficacy are still inconclusive.

Incident left bundle branch block predicts cardiovascular events and death in hypertensive patients with left ventricular hypertrophy. The LIFE Study

Aim: Whether incident left bundle branch block (LBBB) is associated with increased cardiovascular (CV) morbidity and mortality in treated hypertensive patients with left ventricular hypertrophy (LVH) is unknown. Thus, the present study aimed to examine CV outcomes of incident LBBB in treated hypertensive patients with LVH. Methods: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, 9,193 hypertensive patients with LVH on screening electrocardiogram (ECG) were randomized to losartan or atenolol based treatment. Participants (n = 8,567) did not have LBBB (Minnesota code 7.1) on baseline ECG. Cox regression models controlling for significant covariates assessed independent associations of incident LBBB with CV events and all-cause mortality during 4.8 years mean follow-up. Results: Annual follow-up ECGs identified 295 patients (3.4%) with incident LBBB associated with male gender (P < 0.05), older age, higher Cornell voltage (both P < 0.005) and history of diabetes, isolated systolic hypertension and prevalent CV disease. When adjusted for the history of previous CV disease, diabetes, isolated systolic hypertension, the Framingham risk score, ECG-LVH and randomized study treatment, Cox regression models showed that incident LBBB predicted higher risk of the composite endpoint CV death, myocardial infarction and stroke [hazard ratio (HR) 1.9, 95% confidence intervals (CIs) 1.3–2.9, P < 0.001], CV death (HR 3.0, 95% CIs 1.84–5.0, P < 0.001), heart failure (HR 3.6, 95% CIs 1.9–6.6, P < 0.001) and all-cause mortality (HR 3.0, 95% CIs 2.0–4.3, P < 0.001). Conclusions: These data suggest that among hypertensive patients with ECG-LVH receiving aggressive antihypertensive therapy, incident LBBB independently predicts increased risk of subsequent CV events including congestive heart failure and CV and all-cause mortality (ClinicalTrials.gov identifier: NCT00338260).

Platelet FcγRIIa Expression in Ischemic Stroke: A Marker of Increased Platelet Reactivity

Background Platelet FcγRIIa amplifies platelet activation and, thus, increased expression identifies patients with increased platelet reactivity. Previous work has demonstrated that platelet FcγRIIa can identify patients at high and low risk of subsequent cardiovascular events after myocardial infarction (MI). This study was designed to compare platelet expression of FcγRIIa in patients with stroke and transient ischemic attack (TIA) with that in patients with a recent MI. Methods Patients were enrolled based on an admitting diagnosis of stroke/TIA, and the discharge diagnosis was used to categorize patients into stroke/TIA (n=99) and other causes of neurologic dysfunction (hemorrhagic, trauma, toxic, and seizure; n=14). Patients with stroke/TIA were divided into embolic (both cardioembolic and thromboembolic; n=32) and not embolic causes (n=67). Results were compared with platelet FcγRIIa expression in patients with recent MI from a previous study (n=197). Platelet expression of FcγRIIa (molecules of FcγRIIa/platelet) was quantified with the use of flow cytometry. Results are mean±SD. Results Platelet expression of FcγRIIa was similar in patients with ischemic (both embolic and nonembolic) stroke/TIA (11 332±4127), embolic (11 204±3889) and nonembolic (11 393±4263) causes, and MI (11 479±2405). Patients with other causes of neurologic dysfunction had modestly but not significantly lower platelet expression of FcγRIIa (9389±2883; P =0.13). Conclusions Platelet expression of FcγRIIa was similar in patients with stroke/TIA and recent MI. These results support future studies designed to determine whether platelet FcγRIIa expression can discriminate risk of subsequent stroke/TIA and its potential use as a precision tool capable of guiding individualized treatment decisions.

Abstract P125: Change In Low-density Lipoprotein Cholesterol And Risk Of Subsequent Cardiovascular Events Among Patients With Myocardial Infarction

Background: Among patients who experience a myocardial infarction (MI), elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for experiencing a subsequent cardiovascular (CV) event; however, real-world evidence is lacking in regard to how changes in LDL-C levels after a MI hospitalization are related to subsequent CV events. Methods: Adults with a hospitalized MI and an available baseline LDL-C (closest LDL-C within 2 years prior to hospital discharge) between 2012 and 2018 within a 27-county region across MN and WI were included for study. For each LDL-C measurement during follow-up (starting with the first LDL-C >30 days after baseline and ≤1-year post-discharge), percent change from baseline LDL-C was calculated. Patients were followed for subsequent CV events (composite endpoint 1: MI, ischemic stroke [IS], coronary artery bypass grafting [CABG], percutaneous coronary intervention [PCI]; composite endpoint 2: MI, IS, CABG, PCI, CV death). Cox models were used to evaluate the association between time-dependent LDL-C percent change and CV events, stratified by baseline LDL-C (<70, 70-99, ≥100 mg/dL). Results: Among 3,034 MI patients identified, 740 (24%), 940 (31%) and 1354 (45%) had a baseline LDL-C <70, 70-99 and ≥100 mg/dL, respectively. After a mean follow-up of 3.4 years, 471 and 667 patients experienced the composite endpoint 1 and 2, respectively. After covariate adjustment, a trend towards a lower risk of CV events with decreasing LDL-C from baseline, compared to those with no change or an increase in LDL-C, was observed among those with a LDL-C <70 and > 100 mg/dl but not in those with a LDL-C 70-99 mg/dL (Table). Conclusions: In a population-based cohort of MI patients, there is evidence that patients with a decrease in LDL-C after MI may have a reduced risk of subsequent CV events. These results underscore the importance of lowering LDL-C after a MI and may help to identify subgroups at highest risk for additional CV events and those who may benefit from targeted LDL-C treatment recommendations.

Incident Cardiovascular Disease Among Adults With Cancer: A Population-Based Cohort Study

BackgroundPatients with cancer and cancer survivors are at increased risk for incident heart failure, but there are conflicting data on the long-term risk for other cardiovascular events and how such risk may vary by cancer site. ObjectivesThe aim of this study was to determine the impact of a new cancer diagnosis on the risk for fatal and nonfatal cardiovascular events. MethodsUsing administrative health care databases, a population-based retrospective cohort study was conducted among 4,519,243 adults residing in Alberta, Canada, from April 2007 to December 2018. Participants with new cancer diagnoses during the study period were compared with those without cancer with respect to risk for subsequent cardiovascular events (cardiovascular mortality, myocardial infarction, stroke, heart failure, and pulmonary embolism) using time-to-event survival models after adjusting for sociodemographic data and comorbidities. ResultsA total of 224,016 participants with new cancer diagnoses were identified, as well as 73,360 cardiovascular deaths and 470,481 nonfatal cardiovascular events during a median follow-up period of 11.8 years. After adjustment, participants with cancer had HRs of 1.33 (95% CI: 1.29-1.37) for cardiovascular mortality, 1.01 (95% CI: 0.97-1.05) for myocardial infarction, 1.44 (95% CI: 1.41-1.47) for stroke, 1.62 (95% CI: 1.59-1.65) for heart failure, and 3.43 (95% CI: 3.37-3.50) for pulmonary embolism, compared with participants without cancer. Cardiovascular risk was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system and hematologic malignancies. ConclusionsA new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site. These findings highlight the need for a collaborative approach to health care for patients with cancer and cancer survivors.

Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study.

To determine whether surviving a first sepsis hospitalization is associated with long-term cardiovascular events. Population-based matched cohort study conducted in Ontario, Canada (2008-2017). Adult survivors (older than 18years) of a first sepsis hospitalization were matched to adult survivors of a non-sepsis hospitalization using hard-matching and propensity score methods. Patients with pre-existing cardiovascular disease were excluded. The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5years of follow-up. Secondary outcomes included venous thromboembolism and all-cause death. Cox proportional hazards models with robust standard errors were used to estimate the association of sepsis with all outcomes of interest; hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Sensitivity analyses included Fine and Gray models to account for the competing risk of all-cause death and probabilistic bias analyses. 254,241 adult sepsis survivors were matched to adult survivors of non-sepsis hospitalization episodes. Sepsis survivors experienced an increased hazard of major cardiovascular events compared to non-sepsis survivors (HR 1.30; 95% CI 1.27-1.32), which was more pronounced in younger patients (HR 1.66; 95% CI 1.36-2.02 for patients aged 40 or younger; HR 1.21; 95% CI 1.18-1.24 for patients older than 80years). Sepsis survivors also faced an increased hazard of venous thromboembolism (HR 1.61; 95% CI 1.55-1.67) and all-cause death (HR 1.26; 95% CI 1.25-1.27). Sensitivity analyses yielded consistent results. Adult sepsis survivors experience an increased hazard of major cardiovascular events compared to survivors of a non-sepsis hospitalization.

Early systolic lengthening in patients with ST-elevation myocardial infarction: a novel tool for risk stratification

Abstract Funding Acknowledgements Type of funding sources: None. Background After an ST-elevation myocardial infarction (STEMI), the risk of subsequent cardiovascular events is high. Risk stratification at index hospitalization remains a core challenge, especially in patients with subtle changes in LV function. Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force and it has been correlated with infarct size and prognosis in STEMI patients with mildly impaired LV function. In this study, we aimed to evaluate the correlation of ESL with common echocardiographic parameters and its prognostic value in STEMI patients with preserved LV function. Methods We retrospectively included all the patients admitted to an intensive care unit with STEMI and a left ventricle ejection fraction ≥55% from January to June of 2016. Patients with inadequate image quality for speckle tracking echocardiographic examination were excluded (n = 14). We evaluated the ESL index, defined as follows: [−100×(peak positive systolic strain/peak negative strain in cardiac cycle)], and ESL duration. Results A total of 37 patients were included in the study. Mean age was 63 ± 12 years with a male preponderance (81%). All patients were submitted to complete revascularization. Median values of the ESL index and ESL duration were 7% (IQR, 4%–10%) and 37 msec (IQR, 21–55 msec), respectively. No significant differences were found between ESL index and ESL duration groups, except for a higher prevalence of heart failure at hospitalization in both highest groups, and women were more prevalent in the ESL index higher group (Tables 1 and 2). ESL index was correlated with post-systolic index (PSI) (r2 = 0.34, p = 0.04) and showed a weak correlation with E/A ratio (r2=-0.37, p = 0.02). ESL duration was correlated with ESL index (r2 = 0.76, p < 0.001) and PSI (r2 = 0.43, p = 0.008). During a median follow-up of 3.2 years (interquartile range, 2.9–3.4 years), 7 (18.9%) patients experienced major adverse cardiovascular events (MACE), a composite of heart failure admission, myocardial infarction, and all-cause mortality Both ESL index (HR 2.5; 95%CI 1.2–5.3; P = 0.02) and ESL duration (HR 1.7; 95%CI 1.1–2.7; P = 0.02) were independent predictors of MACE. Both associations remained significant after adjusting for clinical confounders. Conclusions In our cohort of STEMI patients with preserved LV function, assessment of ESL yielded important and significant prognostic information on MACE. ESL may be a useful tool to enhance routine risk stratification in this population. Abstract TABLE 1 Abstract TABLE 2

Interaction between smoking and diabetes in relation to subsequent risk of cardiovascular events

BackgroundWhether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD.MethodsThis nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011–2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline.ResultsStudy participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17–1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01–1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71–1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77–2.14) or former smokers (HR, 1.22; 95% CI, 0.66–2.28).ConclusionsSmoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort.

BackgroundCarotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes.Methods and ResultsWe studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT.ConclusionsIn the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.

Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial

Introduction: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. Aims: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. Methods: WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. Results: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06–7.96), p value <0.0001. Conclusion: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.