Search

Complement factor H (CFH) is an important regulator of the complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to downregulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism has been suggested to influence the ability of CFH to bind CRP. We hypothesized that the combined presence of unfavorable CRP and CFH genetic profiles is associated with risk of myocardial infarction (MI). The Rotterdam Study is a population-based cohort study in 7,983 men and women aged ≥55 years. The CFH Tyr402His (rs1061170) polymorphism was determined (His402 allele 37%), and using 3 tagging polymorphisms (rs1130864, rs1205, and rs3093068), CRP haplotypes were inferred (1 = CTC, 2 = TCC, 3 = CCC, 4 = CCG; frequencies of 33%, 32%, 30%, and 6%, respectively). Participants were grouped by CFH genotype (TyrTyr [reference], TyrHis, and HisHis) and CRP haplotype (haplotype 1 homozygotes [reference], haplotype 2 carriers, haplotype 3 carriers, and haplotype 4 carriers), which resulted in a total of 12 groups. CFH His402 homozygotes who were also CRP haplotype 3 carriers had an age- and gender-adjusted hazard ratio of 5.9 (95% confidence interval 2.1 to 16.5) to develop MI compared with the reference group. In conclusion, this population-based study suggests that the combined presence of unfavorable CFH and CRP genetic profiles is associated with risk of MI. [Copyright &y& Elsevier]

The relation between C-reactive protein (CRP) and coronary atherosclerosis is not fully understood. This study aims to investigate the associations among high-sensitivity CRP, coronary plaque burden, and the presence of high-risk coronary lesions as measured by intravascular ultrasound (IVUS) and 1-year cardiovascular outcome. Between 2008 and 2011, grayscale and virtual histology IVUS imaging of a nonculprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris. Primary end point consisted of 1-year major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or unplanned coronary revascularization. After adjustment for established cardiac risk factors, baseline CRP levels were independently associated with higher coronary plaque burden (p[0.002) and plaque volume (p[0.002) in the imaged coronary segment. CRP was also independently associated with the presence of large lesions (plaque burden ⩾70%; p [ 0.030) but not with the presence of stenotic lesions (minimal luminal area ⩽4.0 mm²; p [ 0.62) or IVUS virtual histology-derived thin-cap fibroatheroma lesions (p [ 0.36). Cumulative incidence of 1-year MACE was 9.7%. CRP levels >3 mg/L were independently associated with a higher incidence of MACE (hazard ratio 2.17, 95% confidence interval [CI] 1.01 to 4.67, p[0.046) and of all-cause mortality and ACS only (hazard ratio 3.58, 95% CI 1.04 to 13.0, p[0.043), compared with CRP levels <1 mg/L. In conclusion, in patients who underwent coronary angiography, high-sensitivity CRP is a marker of coronary plaque burden but is not related to the presence of virtual histologyderived thin-cap fibroatheroma lesions and stenotic lesions. CRP levels >3 mg/L are predictive for adverse cardiovascular outcome at 1 year. [ABSTRACT FROM AUTHOR]

Appropriate risk stratification of patients with established, stable coronary artery disease could contribute to the prevention of recurrent cardiovascular events. The purpose of the present study was to develop and validate risk prediction models for various cardiovascular end points in the EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) database, consisting of 12,218 patients with established coronary artery disease, with a median follow-up of 4.1 years. Cox proportional hazards models were used for model development. The end points examined were cardiovascular mortality, noncardiovascular mortality, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, resuscitated cardiac arrest, and combinations of these end points. The performance measures included Nagelkerke's R2, time-dependent area under the receiver operating characteristic curves, and calibration plots. Backward selection resulted in a prediction model for cardiovascular mortality (464 events) containing age, current smoking, diabetes mellitus, total cholesterol, body mass index, previous myocardial infarction, history of congestive heart failure, peripheral vessel disease, previous revascularization, and previous stroke. The model performance was adequate for this end point, with a Nagelkerke R2 of 12%, and an area under the receiver operating characteristic curve of 0.73. However, the performance of models constructed for nonfatal and combined end points was considerably worse, with an area under the receiver operating characteristic curve of about 0.6. In conclusion, in patients with established coronary artery disease, the risk of cardiovascular mortality during longer term follow-up can be adequately predicted using the clinical characteristics available at baseline. However, the prediction of nonfatal outcomes, both separately and combined with fatal outcomes, poses major challenges for clinicians and model developers. [ABSTRACT FROM AUTHOR]

Complete revascularization (CR) in patients with acute coronary syndromes (ACS) and multivessel disease (MVD) improves clinical outcomes compared with culprit-only revascularization, but the optimal timing for non-culprit lesions treatment remains unclear. This study evaluated patients presenting with ACS and MVD admitted between January 2015 and September 2021 at the Erasmus University Medical Center. Clinical outcomes were compared between immediate and staged CR in terms of major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause mortality, myocardial infarction, stroke, and any unplanned revascularization. A total of 1,400 patients presenting with ACS and MVD who underwent immediate or staged CR were included in this study. Using 1/many propensity score matching without replacement, 299 patients in the staged CR group were matched to 598 patients in the immediate CR group (mean 1:2 ratio), rendering a total of 897 patients for analysis. The median follow-up period was 648 days. MACCE rate was significantly higher in the staged CR group than in the immediate CR group (adjusted hazard ratio [95% confidence interval] 1.60 [1.05 to 2.45], p = 0.03). Furthermore, number of stents, stent length, and contrast usage were significantly greater in the staged revascularization group. Immediate CR was associated with less risk of MACCE than was staged CR. Staged CR required overall more contrast and stent material., Competing Interests: Declaration of Competing Interest Dr. Diletti reports a relation with Erasmus Medical Center that includes funding grants. Dr. Daemen reports a relation with Erasmus Medical Center that includes consulting or advisory, funding grants, and speaking and lecture fees. Dr. Van Mieghem reports a relation with Erasmus Medical Center that includes funding grants. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sex-specific thresholds of aortic valve calcification (AVC) correlate with aortic stenosis (AS) and may complement echocardiography to determine AS severity. Importantly, current guideline-recommended thresholds of AVC scores derived by multislice computed tomography do not distinguish between bicuspid and tricuspid aortic valves. The objective of this study was to evaluate the sex-specific differences in the amount of AVC in patients with severe AS and tricuspid (TAV) versus bicuspid (BAV) aortic valve morphologies, retrospectively evaluated by 2 tertiary care institutions. The inclusion criteria comprised patients with severe AS and a left ventricular ejection fraction ≥50% and suitable imaging examinations. The study included 1,450 patients (723 men; 49.9%) with severe AS, including 1,335 patients with TAV (92.1%) and 115 with BAV (17.9%). The calculated Agatston score was higher in BAV patients (men: BAV 4,358 [2,644 to 6,005] AU vs TAV 2,643 [1,727 to 3,794] AU, p <0.01; women: BAV 2,174 [1,330 to 4,378] AU vs TAV 1,703 [964 to 2,534] AU, p <0.01), also when indexed for valve dimensions and body surface area (men: BAV 2,227 [321 to 3,105] AU/m 2 vs TAV 1,333 [872 to 1,913] AU/m 2 , p <0.01; women: BAV 1,326 [782 to 2,148] AU/m 2 vs TAV 930 [546 to 1,456] AU/m 2 , p <0.01). Differences between the BAV- and TAV-derived Agatston score was more prominent in concordant severe AS. In conclusion, sex-specific Agatston scores in severe AS were approximately 1/3 higher in patients with BAV than in patients with TAV for both women and men. Optimal AVC thresholds should be adjusted for BAV, also respecting considerable prognostic implications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073., Competing Interests: Disclosures Dr. van der Harst reports a relation with Dutch Heart Foundation that includes funding grants; reports a relation with ZonMw that includes funding grants; reports a relation with NWO that includes funding grants; and reports a relation with Siemens Healthineers that includes funding grants. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The optimal revascularization strategy for residual coronary stenosis following primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) remains controversial. This is a retrospective single-centre study including patients with STEMI and MVD. Based on the revascularization strategy, 3 groups were identified: (1) culprit only (CO), (2) ad hoc multivessel revascularization (MVR), and (3) staged MVR. Clinical outcomes were compared in terms of major adverse cardiac events (MACE), a composite of cardiac death, any myocardial infarction, and any unplanned revascularization at a long-term follow-up. A total of 958 patients were evaluated, 489 in the CO, 254 in the ad hoc, and 215 in the staged group. In the staged group, 65.6% of the patients received planned percutaneous coronary intervention, 9.7% coronary artery bypass grafting, 8.4% no further intervention after lesion reassessment, and in 16.3% an event occurred before the planned procedure. At 1,095 days, MACE was 36.1%, 16.7%, and 31% for CO, ad hoc, and staged groups, respectively. A MVR strategy was associated with lower rate of all-cause death compared with CO (HR 0.50; 95%CI [0.31 to 0.80]; p = 0.004). Complete revascularization reduced the rate of MACE (HR 0.30 [0.21 to 0.43] p < 0.001) compared with incomplete revascularization. Ad hoc MVR had lower rate of MACE compared with staged MVR (HR 0.61 [0.39 to 0.96] p = 0.032) mainly driven by less unplanned revascularizations. In conclusion, in patients with STEMI and MVD, complete revascularization reduced the risk of MACE. Ad hoc MVR appeared a reasonable strategy with lower contrast and stent usage and costs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The etiology of chest pain in hypertrophic cardiomyopathy (HC) is diverse and includes coronary artery disease (CAD) as well as HC-specific causes. Myocardial bridging (MB) has been associated with HC, chest pain, and accelerated atherosclerosis. We compared HC patients with age-, gender- and CAD pre-test probability-matched outpatients presenting with chest pain to investigate differences in the presence of MB and CAD using coronary computed tomography angiography (CCTA). We studied 84 HC patients who underwent CCTA and compared these with 168 matched controls (age 54 ± 11 years, 70% men, pre-test probability 12% [5% to 32%]). MB, calcium score, plaque morphology and presence and extent of CAD were assessed for each patient. Linear mixed models were used to assess differences between cases and controls. MB was more often seen in HC patients (50% vs 25%, p <0.001). Calcium score and the presence of obstructive CAD were similar in both groups (9 [0 to 225] vs 4 [0 to 82] and 18% vs 19%; p = 0.22 and p = 0.82). In the HC group, MB was associated with pathogenic DNA variants (p = 0.04), but not with the presence of chest pain (74% vs 76%, p = 0.8), nor with worse outcome (log-rank p = 0.30). In conclusion, the prevalence and extent of CAD was equal among patients with and without HC, demonstrating that pre-test risk prediction using the CAD Consortium clinical risk score performs well in HC patients. MB was twice as prevalent in the HC group compared with matched controls, but was not associated with chest pain or decreased event-free survival in these patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gender has been proposed to impact the phenotype and prognosis of hypertrophic cardiomyopathy (HC). Our aims were to study gender differences in the clinical presentation, phenotype, genotype, and outcome of HC. This retrospective single-center cohort study included 1,007 patients with HC (62% male, 80% genotyped) evaluated between 1977 and 2017. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard regression models. At first evaluation, female patients presented more often with symptoms (43% vs 35%, p = 0.01), were older than male patients (56 ± 16 vs 49 ± 15 years, p <0.001), and more frequently had hypertension (38% vs 27%, p <0.001), left ventricular outflow tract obstruction (37% vs 27%, p <0.001), and impaired left ventricular systolic (17% vs 11%, p = 0.01) and diastolic (77% vs 62%, p <0.001) function. Overall, the genetic yield was similar between genders (54% vs 51%, p = 0.4); however, in patients ≥70 years, the genetic yield was less in women (15% vs 36%, p = 0.03). During 6.8-year follow-up (interquartile range 3.2 to 10.9), female gender was not independently associated with all-cause mortality (HR 1.25 [0.91 to 1.73]), cardiovascular mortality (HR 1.22 [0.83 to 1.79]), heart failure-related mortality (HR 1.77 [0.95 to 3.27]), or sudden cardiac death (SCD) and/or aborted SCD (HR 0.75 [0.44 to 1.30]). Interventions and nonfatal clinical events did not differ between the genders. In conclusion, female patients with HC present at a more advanced age with a different clinical, phenotypic, and genetic status. There is no independent association between female gender and all-cause mortality, cardiovascular mortality, heart failure-related mortality, or SCD., (Copyright © 2018. Published by Elsevier Inc.)

Left ventricular assist devices (LVAD) are increasingly used, especially as destination therapy in in older patients. The aim of this study was to evaluate the effect of age on renal function and mortality in the first year after implantation. A retrospective multicenter cohort study was conducted, evaluating all LVAD patients implanted in the 2 participating centers (age ≥18 years). Patients were stratified according to the age groups <45, 45-54, 55-64, and ≥65 years old. Overall, 241 patients were included (mean age 52.4 ± 12.9 years, 76% males, 33% destination therapy). The mean estimated Glomerular Filtration Rate (eGFR) at 1 year was 85, 72, 69, and 49 mL/min per 1.73 m 2 in the age groups <45(n = 65, 27%), 45-54(n = 52, 22%), 55-64(n = 87, 36%), and ≥65 years (n = 37, 15%) p <0.001)), respectively. Older age and lower eGFR at baseline (p <0.01) were independent predictors of worse renal function at 1 year. The 1-year survival post-implantation was 79%,84%, 68%, and 54% for those in the age group <45, 45-54, 55-64 and ≥65 years (Log-rank p = 0.003). Older age, lower eGFR and, INTERMACS class I were independent predictors of 1-year mortality. Furthermore, older patients (age > 60 years) with an impaired renal function (eGFR <55 mL/min per 1.73 m 2 ) had a 5-fold increased hazard ratio for mortality during the first year after implantation (p <0.001). In conclusion, age >60 years is an independent predictor for an impaired renal function and mortality. Older age combined with reduced renal function pre-implantation had a cumulative adverse effect on survival in patients receiving a LVAD., (Copyright © 2017 Elsevier Inc. All rights reserved.)