Antihypertensive Drugs for the Prevention of Atrial Fibrillation: A Drug Target Mendelian Randomization Study.

BACKGROUND: We investigated the potential impact of antihypertensive drugs for atrial fibrillation (AF) prevention through a drug target Mendelian randomization study to avoid the potential limitations of clinical studies. METHODS: Validated published single-nucleotide polymorphisms (SNPs) that mimic the action of 12 antihypertensive drug classes, including alpha-adrenoceptor blockers, adrenergic neuron blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta-adrenoceptor blockers, centrally acting antihypertensive drugs, calcium channel blockers, loop diuretics, potassium-sparing diuretics and mineralocorticoid receptor antagonists, renin inhibitors, thiazides and related diuretic agents, and vasodilators were used. We estimated, via their corresponding gene and protein targets, the downstream effect of these drug classes to prevent AF via systolic blood pressure using 2-sample Mendelian randomization analyses. The SNPs were extracted from 2 European genome-wide association studies for the drug classes (n=317 754; n=757 601) and 1 European genome-wide association study for AF (n=1 030 836). RESULTS: Drug target Mendelian randomization analyses supported the significant preventive causal effects of lowering systolic blood pressure per 10 mm Hg via alpha-adrenoceptor blockers (n=11 SNPs; odds ratio [OR], 0.34 [95% CI, 0.21-0.56]; P=2.74×10-05), beta-adrenoceptor blockers (n=17 SNPs; OR, 0.52 [95% CI, 0.35-0.78]; P=1.62×10-03), calcium channel blockers (n=49 SNPs; OR, 0.50 [95% CI, 0.36-0.70]; P=4.51×10-05), vasodilators (n=19 SNPs; OR, 0.53 [95% CI, 0.34-0.84]; P=7.03×10-03), and all 12 antihypertensive drug classes combined (n=158 SNPs; OR, 0.64 [95% CI, 0.54-0.77]; P=8.50×10-07) on AF risk. CONCLUSIONS: Our results indicated that lowering systolic blood pressure via protein targets of various antihypertensive drugs seems promising for AF prevention. Our findings inform future clinical trials and have implications for repurposing antihypertensive drugs for AF prevention.

Electrocardiographic parameters and the risk of new-onset atrial fibrillation in the general population: the Rotterdam Study.

AIMS: We aimed to assess the (shape of the) association and sex differences in the link between electrocardiographic parameters and new-onset atrial fibrillation (AF). METHODS AND RESULTS: A total of 12 212 participants free of AF at baseline from the population-based Rotterdam Study were included. Up to five repeated measurements of electrocardiographic parameters including PR, QRS, QT, QT corrected for heart rate (QTc), JT, RR interval, and heart rate were assessed at baseline and follow-up examinations. Cox proportional hazards- and joint models, adjusted for cardiovascular risk factors, were used to determine the (shape of the) association between baseline and longitudinal electrocardiographic parameters with new-onset AF. Additionally, we evaluated potential sex differences. During a median follow-up of 9.3 years, 1282 incident AF cases occurred among 12 212 participants (mean age 64.9 years, 58.2% women). Penalized cubic splines revealed that associations between baseline electrocardiographic measures and risk of new-onset AF were generally U- and N-shaped. Sex differences in terms of the shape of the various associations were most apparent for baseline PR, QT, QTc, RR interval, and heart rate in relation to new-onset AF. Longitudinal measures of higher PR interval [fully adjusted hazard ratio (HR), 95% confidence interval (CI), 1.43, 1.02-2.04, P = 0.0393] and higher QTc interval (fully adjusted HR, 95% CI, 5.23, 2.18-12.45, P = 0.0002) were significantly associated with new-onset AF, in particular in men. CONCLUSION: Associations of baseline electrocardiographic measures and risk of new-onset AF were mostly U- and N-shaped. Longitudinal electrocardiographic measures of PR and QTc interval were significantly associated with new-onset AF, in particular among men.

Risk of cancer after ST-segment-elevation myocardial infarction.

Analyses from administrative databases have suggested an increased cancer incidence among individuals who experienced a myocardial infarction, especially within the first 6 months. It remains unclear to what extent this represents an underlying biological link, or can be explained by detection of pre-symptomatic cancers and shared risk factors. Cancer incidence among 1809 consecutive patients surviving hospitalization for thrombotic ST-segment-elevation myocardial infarction (STEMI; mean age 62.6 years; 26% women; 115 incident cancers) was compared to the cancer incidence among 10,052 individuals of the general population (Rotterdam Study; mean age 63.1 years; 57% women; 677 incident cancers). Pathology-confirmed cancer diagnoses were obtained through identical linkage of both cohorts with the Netherlands Cancer Registry. Cox models were used to obtain hazards ratios (HRs) adjusted for factors associated with both atherosclerosis and cancer. Over 5-year follow-up, there was no significant difference in the incidence of cancer between STEMI patients and the general population (HR 0.96, 95% CI 0.78-1.19). In the first 3 months after STEMI, cancer incidence was markedly higher among STEMI patients compared to the general population (HR 2.45, 95% CI 1.13-5.30), which gradually dissolved during follow-up (P-for-trend 0.004). Among STEMI patients, higher C-reactive protein, higher platelet counts, and lower hemoglobin were associated with cancer incidence during the first year after STEMI (HRs 2.93 for C-reactive protein > 10 mg/dL, 2.10 for platelet count > 300*109, and 3.92 for hemoglobin < 7.5 mmol/L). Although rare, thrombotic STEMI might be a paraneoplastic manifestation of yet to be diagnosed cancer, and is hallmarked by a pro-inflammatory status and anemia.Trial registration Registered into the Netherlands National Trial Register and WHO International Clinical Trials Registry Platform under shared catalogue number NTR6831.

Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease.

BACKGROUND: Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control. AIMS: This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event. METHODS AND RESULTS: Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS. Patients aged ≥45 years at ≥6 months after coronary event were included. The SMART-REACH score was used to estimate 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events with current treatment and potential risk reduction and gains in event-free years with maximal treatment (lifestyle and pharmacological). In 3230 atherosclerotic cardiovascular disease patients (24% women), at median interquartile range (IQR) 1.1 years (1.0-1.8) after index event, 10-year risk was median (IQR) 20% (15-27%) and lifetime risk 54% (47-63%). Whereas 70% used conventional medication, 82% had ≥1 drug-modifiable risk factor not on target. Furthermore, 91% had ≥1 lifestyle-related risk factor not on target. Maximizing therapy was associated with a potential reduction of median (IQR) 10-year risk to 6% (4-8%) and of lifetime risk to 20% (15-27%) and a median (IQR) gain of 7.3 (5.4-10.4) atherosclerotic cardiovascular disease event-free years. CONCLUSIONS: Amongst patients with atherosclerotic cardiovascular disease, maximizing current, guideline-based preventive therapy has the potential to mitigate a large part of their risk of recurrent events and to add a clinically important number of event-free years to their lifetime.

Patients with heart disease are at high risk of new cardiac events. This study amongst 3230 patients who had a heart attack or received a stent or bypass surgery shows missed potential for healthy life after a heart attack. The average age of study patients was 61 years, and 24% were women. At 1 year after the cardiac event, nearly one in three (30%) continued smoking, 79% were overweight, 45% reported insufficient physical activity, 40% had high blood pressure, and 65% had a too high LDL ('bad') cholesterol. We calculated that adherence to lifestyle advice and medications could on average halve the risk for another heart attack and add over 7 healthy years of life after a heart attack. This highlights the importance of healthy lifestyle and medication adherence after a heart attack. Key finding:• adherence to lifestyle advice and medications could add over 7 healthy years of life after a heart attack.

Heart rate variability and atrial fibrillation in the general population: a longitudinal and Mendelian randomization study.

BACKGROUND: Sex differences and causality of the association between heart rate variability (HRV) and atrial fibrillation (AF) in the general population remain unclear. METHODS: 12,334 participants free of AF from the population-based Rotterdam Study were included. Measures of HRV including the standard deviation of normal RR intervals (SDNN), SDNN corrected for heart rate (SDNNc), RR interval differences (RMSSD), RMSSD corrected for heart rate (RMSSDc), and heart rate were assessed at baseline and follow-up examinations. Joint models, adjusted for cardiovascular risk factors, were used to determine the association between longitudinal measures of HRV with new-onset AF. Genetic variants for HRV were used as instrumental variables in a Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary-level data. RESULTS: During a median follow-up of 9.4 years, 1302 incident AF cases occurred among 12,334 participants (mean age 64.8 years, 58.3% women). In joint models, higher SDNN (fully-adjusted hazard ratio (HR), 95% confidence interval (CI) 1.24, 1.04-1.47, p = 0.0213), and higher RMSSD (fully-adjusted HR, 95% CI 1.33, 1.13-1.54, p = 0.0010) were significantly associated with new-onset AF. Sex-stratified analyses showed that the associations were mostly prominent among women. In MR analyses, a genetically determined increase in SDNN (odds ratio (OR), 95% CI 1.60, 1.27-2.02, p = 8.36 × 10-05), and RMSSD (OR, 95% CI 1.56, 1.31-1.86, p = 6.32 × 10-07) were significantly associated with an increased odds of AF. CONCLUSION: Longitudinal measures of uncorrected HRV were significantly associated with new-onset AF, especially among women. MR analyses supported the causal relationship between uncorrected measures of HRV with AF. Our findings indicate that measures to modulate HRV might prevent AF in the general population, in particular in women. AF; atrial fibrillation, GWAS; genome-wide association study, IVW; inverse variance weighted, MR; Mendelian randomization, MR-PRESSO; MR-egger and mendelian randomization pleiotropy residual sum and outlier, RMSSD; root mean square of successive RR interval differences, RMSSDc; root mean square of successive RR interval differences corrected for heart rate, SDNN; standard deviation of normal to normal RR intervals, SDNNc; standard deviation of normal to normal RR intervals corrected for heart rate, WME; weighted median estimator. aRotterdam Study n=12,334 bHRV GWAS n=53,174 cAF GWAS n=1,030,836.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

Disentangling the association between kidney function and atrial fibrillation: a bidirectional Mendelian randomization study.

BACKGROUND: The potential bidirectional causal association between kidney function and atrial fibrillation (AF) remains unclear. METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis. From multiple genome-wide association studies (GWAS), we retrieved genetic variants associated with kidney function (estimated glomerular filtration rate based on creatinine (eGFRcreat), blood urea nitrogen (BUN), chronic kidney disease (CKD stage ≥G3): n = 1,045,620, eGFR based on cystatin C: n = 24,063-32,861, urine albumin-to-creatinine ratio (UACR), and microalbuminuria: n = 564,257), and AF (n = 1,030,836). The inverse-variance weighted method was used as our main analysis. RESULTS: MR analyses supported a causal effect of CKD (n = 9 SNPs, odds ratio (OR): 1.10, 95% confidence interval (CI): 1.04-1.17, p-value = 1.97 × 10-03), and microalbuminuria (n = 5 SNPs, OR: 1.26, 95% CI: 1.10-1.46, p-value = 1.38 × 10-03) on AF risk. We also observed a causal effect of AF on eGFRcreat (n = 97 SNPs, OR: 1.00, 95% CI: 1.00-1.00, p-value = 6.78 × 10-03), CKD (n = 107 SNPs, OR: 1.06, 95% CI: 1.03-1.09, p-value = 2.97 × 10-04), microalbuminuria (n = 83 SNPs, OR: 1.07, 95% CI: 1.04-1.09, p-value = 2.49 × 10-08), and a suggestive causal effect on eGFRcys (n = 103 SNPs, OR: 0.99, 95% CI: 0.99-1.00, p-value = 4.61 × 10-02). Sensitivity analyses, including weighted median estimator, MR-Egger, the MR pleiotropy residual sum and outlier test, and excluding genetic variants associated with possible confounders and/or horizontal mediators (myocardial infarction/coronary artery disease, heart failure) indicated that these findings were robust. CONCLUSIONS: Our results supported a bidirectional causal association between kidney function and AF. The shared genetic architecture between kidney dysfunction and AF might represent potential important therapeutic targets to prevent both conditions in the general population.

Comparison of guidelines for diagnosing suspected stable angina and the additional value of the calcium score.

Background The performance of current diagnostic algorithms of the American College of Cardiology/American Heart Association (ACC/AHA), National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) in patients with stable chest pain and coronary artery calcium (CAC) remains a matter of debate. We compared their merits in patients with CAC and investigated the additional value of the CAC score to improve diagnostic accuracy and risk stratification. Methods and results Patient data were obtained from a prospective registry of 642 consecutive patients. Mean age 63 (SD 11) years, 50% male. According to the guidelines, low and intermediate/high pre-test probability groups were constructed. Patients were reclassified based on their CAC score. Obstructive coronary artery disease (CAD) was observed in 14%. All models performed modestly in accurately predicting CAD (c-statistic <0.65). After addition of the CAC score, the c-statistic of the NICE model increased to 0.75 (95% confidence interval (CI) 0.73-0.78) which was just non-significant compared to the ESC model (0.71 95% CI 0.67-0.74) and performed significantly better than ACC/AHA (0.68 (95% CI 0.64-0.72)). After reclassification more than 50% of patients were classified low risk in NICE and ESC, while the prevalence of obstructive CAD (4.8% and 5.2% respectively) did not increase. Conclusions Addition of the CAC score to the studied models improved the ability to safely rule-out obstructive CAD and identified other patients at high risk for future coronary artery events. These results suggest that incorporating CAC score will lead to substantially less downstream testing and lower costs.

Recommendations and Associated Levels of Evidence for Statin Use in Primary Prevention of Cardiovascular Disease: A Comparison at Population Level of the American Heart Association/American College of Cardiology/Multisociety, US Preventive Services Task Force, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society Clinical Practice Guidelines.

BACKGROUND: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level. METHODS: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated. RESULTS: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins. CONCLUSIONS: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations.

Preventive implantable cardioverter defibrillator therapy in contemporary clinical practice: need for more stringent selection criteria.

While the efficacy of the intracardiac defibrillators (ICDs) for primary prevention is not disputed, the relevant studies were carried out a long time ago. Most pertinent trials, including MADIT-II, SCD-Heft, and DEFINITE, recruited patients more than 20 years ago. Since then, improved therapeutic modalities including, in addition to cardiac resynchronization therapy, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and, most recently, inhibitors of sodium-glucose cotransporter 2, have lowered present-day rates of mortality and of sudden cardiac death. Thus, nowadays, ICD therapy may be less effective than previously reported, and not as beneficial as many people currently believe. However, criteria for ICD implantation remain very inclusive. The patient must (only) be symptomatic and have ejection fraction (EF) ≤ 35%. The choice of EF 35% is notable because the average EF in all large trials was much lower, and clinical benefit was mainly limited to EF ≤ 30%. This EF cut-off value defines a substantial portion of potential ICD recipients. It seems therefore reasonable to limit ICD eligibility criteria in the EF range 30-35% to patients at highest risk only. We discuss and present some rational criteria to assist the clinician in improving risk stratification for preventive ICD implantation.

Left ventricular remodelling and prognosis after discharge in new-onset acute heart failure with reduced ejection fraction.

AIMS: This study aimed to investigate the left ventricular (LV) remodelling and long-term prognosis of patients with new-onset acute heart failure (HF) with reduced ejection fraction who were pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non-ischaemic aetiology. METHODS AND RESULTS: This cohort study consisted of 111 patients admitted with new-onset acute HF in the period 2008-2016 [62% non-ischaemic aetiology, 48% supported by inotropes, vasopressors, or short-term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22-34)]. LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow-up. Both patients with non-ischaemic and ischaemic HF had significant improvement in LVEF (P < 0.001 and P = 0.004, respectively) with significant higher improvement in those with non-ischaemic HF (17% vs. 6%, P < 0.001). Patients with non-ischaemic HF had reduction in LV end-diastolic and end-systolic diameters (6 and 10 mm, both P < 0.001), but this was not found in those with ischaemic HF [+3 mm (P = 0.09) and +2 mm (P = 0.07), respectively]. During a median follow-up of 4.6 years, 98 patients (88%) did not reach the composite endpoint of LV assist device implantation, heart transplantation, or all-cause mortality, with no difference between with ischaemic and non-ischaemic HF [hazard ratio 0.69 (95% confidence interval 0.19-2.45)]. CONCLUSIONS: Patients with new-onset acute HF with reduced ejection fraction discharged on optimal medical treatment have a good prognosis. We observed a considerable LV remodelling with improvement in LV function and dimensions, starting already at 6 months in patients with non-ischaemic HF but not in their ischaemic counterparts.

Implications of the ACC/AHA risk score for prediction of heart failure: the Rotterdam Study.

BACKGROUND: Despite the growing burden of heart failure (HF), there have been no recommendations for use of any of the primary prevention models in the existing guidelines. HF was also not included as an outcome in the American College of Cardiology/American Heart Association (ACC/AHA) risk score. METHODS: Among 2743 men and 3646 women aged ≥ 55 years, free of HF, from the population-based Rotterdam Study cohort, 4 Cox models were fitted using the predictors of the ACC/AHA, ARIC and Health-ABC risk scores. Performance of the models for 10-year HF prediction was evaluated. Afterwards, performance and net reclassification improvement (NRI) for adding NT-proBNP to the ACC/AHA model were assessed. RESULTS: During a median follow-up of 13 years, 429 men and 489 women developed HF. The ARIC model had the highest performance [c-statistic (95% confidence interval [CI]): 0.80 (0.78; 0.83) and 0.80 (0.78; 0.83) in men and women, respectively]. The c-statistic for the ACC/AHA model was 0.76 (0.74; 0.78) in men and 0.77 (0.75; 0.80) in women. Adding NT-proBNP to the ACC/AHA model increased the c-statistic to 0.80 (0.78 to 0.83) in men and 0.81 (0.79 to 0.84) in women. Sensitivity and specificity of the ACC/AHA model did not drastically change after addition of NT-proBNP. NRI(95%CI) was - 23.8% (- 19.2%; - 28.4%) in men and - 27.6% (- 30.7%; - 24.5%) in women for events and 57.9% (54.8%; 61.0%) in men and 52.8% (50.3%; 55.5%) in women for non-events. CONCLUSIONS: Acceptable performance of the model based on risk factors included in the ACC/AHA model advocates use of this model for prediction of HF risk in primary prevention setting. Addition of NT-proBNP modestly improved the model performance but did not lead to relevant discrimination improvement in clinical risk reclassification.

Path From Clinical Research to Implementation: Endovascular Treatment of Ischemic Stroke in the Netherlands.

Before 2015, endovascular treatment (EVT) for acute ischemic stroke was considered a promising treatment option. Based on limited evidence, it was performed in several dedicated stroke centers worldwide on selected patients. Since 2015, EVT for patients with intracranial large vessel occlusion has quickly been implemented as standard treatment in many countries worldwide, supported by the revised international guidelines based on solid evidence from multiple clinical trials. We describe the development in use of EVT in the Netherlands before, during, and after the pivotal EVT trials. We used data from all patients who were treated with EVT in the Netherlands from January 2002 until December 2018. We undertook a time-series analysis to examine trends in the use of EVT using Poisson regression analysis. Incidence rate ratios per year with 95% CIs were obtained to demonstrate the impact and implementation after the publication of the EVT trial results. We made regional observation plots, adjusted for stroke incidence, to assess the availability and use of the treatment in the country. In the buildup to the MR CLEAN (Multicenter Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands), a slow increase of EVT patients was observed, with 0.2% of all ischemic stroke patients receiving EVT. Before the trial results were formally announced, a statistically significant increase in EVT-treated patients per year was observed (incidence rate ratio, 1.72 [95% CI, 1.46-2.04]), and after the trial publication, an immediate steep increase was seen, followed by a more gradual increase (incidence rate ratio, 2.14 [95% CI, 1.77-2.59]). In 2018, the percentage of ischemic stroke patients receiving EVT increased to 5.8%. A well-developed infrastructure, a pragmatic approach toward the use of EVT in clinical practice, in combination with a strict adherence by the regulatory authorities to national evidence-based guidelines has led to successful implementation of EVT in the Netherlands. Ongoing efforts are directed at further increasing the proportion of stroke patients with EVT in all regions of the country.

Survival After Uncomplicated EVAR in Octogenarians is Similar to the General Population of Octogenarians Without an Abdominal Aortic Aneurysm.

OBJECTIVE: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. METHODS: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. RESULTS: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54). CONCLUSION: After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key.

Stress-Only Adenosine CMR Improves Diagnostic Yield in Stable Symptomatic Patients With Coronary Artery Calcium.

OBJECTIVES: This study assessed whether adenosine stress-only perfusion cardiac magnetic resonance (CMR) following a positive coronary artery calcium (CAC) score improved the diagnostic yield of invasive coronary angiography (CAG) in patients with stable chest pain. The study also established the association between positive CAC scores and stress-induced myocardial ischemia. BACKGROUND: The diagnostic yield of catheterization among patients with suspected coronary artery disease (CAD) is low. Improved patient selection and diagnostic testing are necessary. The CAC score can minimize unnecessary diagnostic testing, and in low-risk patients, normal CMR results have a high negative predictive value. Less comprehensive protocols may be sufficient to guide further work-up. METHODS: A total of 642 consecutive patients (mean age: 63 years; 50% women) with stable chest pain and CAC scores of >0 who were referred for CMR were enrolled. Patients with a perfusion defect were subsequently examined by CAG. Patients were followed up for 1 year. Outcome was obstructive CAD. RESULTS: Obstructive CAD was present in 12% of patients. For CAD diagnosis, the sensitivity of adenosine CMR was 90.9% (95% confidence interval [CI]: 88.7 to 93.1), specificity was 98.7% (95% CI: 97.9 to 99.6), positive predictive value was 92.0% (95% CI: 89.8 to 94.1), and negative predictive value was 98.6% (95% CI: 97.6 to 99.5). A CAC score between 0.1 and 100 without typical angina was associated with obstructive CAD in only 3% of patients. Patients with nonanginal chest pain and a CAC score ≥400 had obstructive CAD (16%). CONCLUSIONS: Stress-only adenosine CMR had high diagnostic accuracy and served as an efficient gatekeeper to CAG in stable patients with a CAC score >0. Patients with CAC scores between 0.1 and 100 could be deferred from further testing in the absence of clinical features that suggested high risk. However, in patients with CAC score ≥400, functional testing should be indicated, regardless of the type of chest pain.

Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects.

BACKGROUND: Coronary artery calcium (CAC) scanning has evolved into an important subclinical prediction method for cardiovascular diseases in asymptomatic subjects. However, the prognostic implication of CAC scanning in symptomatic individuals is less clear. OBJECTIVES: To assess the prognostic utility of CAC in predicting risk of major adverse cardiac events (MACE) in stable patients with suspected CAD. METHODS: We did a systematic electronic literature search for studies presenting original data in CAC score, and reporting cardiovascular events in stable, symptomatic patients as primary outcome. Primary outcome of the meta-analysis was the occurrence of MACE, a composite of late coronary revascularization, hospitalization for unstable angina or heart failure, nonfatal myocardial infarction, and cardiac death or all-cause mortality. Using random effects models, we pooled relative risk ratios of CAC for MACE, and adjusted hazard ratios (HR) of the associations between different CAC strata (CAC 0-100,100-400, and ≥ 400, versus CAC = 0) and incident MACE. RESULTS: We included 19 observational studies (n = 34,041). In total, 1601 events were analyzed, of which 158 in patients with CAC = 0. The pooled relative risk ratio was 5.71 (95%-CI: 3.98;8.19) for subjects with CAC > 0. The pooled estimate of adjusted HRs demonstrated increasing, positive associations, with the strongest association for CAC > 400 (HR: 4.88; 95%-CI: 2.44;9.27). CONCLUSIONS: This meta-analysis demonstrated that increased levels of CAC are strongly and independently associated with increased risk for MACE in stable, symptomatic patients with suspected CAD, showing increasing risk with greater CAC scores. Application of CAC scanning as a prediction method could be useful for a considerable number of such patients.

Blood pressure distribution and control in coronary patients from 24 European countries in the European Society of Cardiology EURoObservational Research Programme European survey of cardiovascular disease prevention and diabetes. EUROASPIRE IV Registry.

BACKGROUND: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey. METHODS: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients. RESULTS: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 ±â€Š9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI). CONCLUSION: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.

Smoking cessation and risk of recurrent cardiovascular events and mortality after a first manifestation of arterial disease.

AIMS: To quantify the relation between smoking cessation after a first cardiovascular (CV) event and risk of recurrent CV events and mortality. METHODS: Data were available from 4,673 patients aged 61 ± 8.7 years, with a recent (≤1 year) first manifestation of arterial disease participating in the SMART-cohort. Cox models were used to quantify the relation between smoking status and risk of recurrent major atherosclerotic cardiovascular events (MACE including stroke, MI and vascular mortality) and mortality. In addition, survival according to smoking status was plotted, taking competing risk of non-vascular mortality into account. RESULTS: A third of the smokers stopped after their first CV event. During a median of 7.4 (3.7-10.8) years of follow-up, 794 patients died and 692 MACE occurred. Compared to patients who continued to smoke, patients who quit had a lower risk of recurrent MACE (adjusted HR 0.66, 95% CI 0.49-0.88) and all-cause mortality (adjusted HR 0.63, 95% CI 0.48-0.82). Patients who reported smoking cessation on average lived 5 life years longer and recurrent MACE occurred 10 years later. In patients with a first CV event >70 years, cessation of smoking had improved survival which on average was comparable to former or never smokers. CONCLUSIONS: Irrespective of age at first CV event, cessation of smoking after a first CV event is related to a substantial lower risk of recurrent vascular events and all-cause mortality. Since smoking cessation is more effective in reducing CV risk than any pharmaceutical treatment of major risk factors, it should be a key objective for patients with vascular disease.