Crystel M. Gijsberts

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

Background Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. Methods We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Results Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. Conclusion The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Gender differences in health-related quality of life in patients undergoing coronary angiography.

Background Health-related quality of life (HRQOL) reflects the general well-being of individuals. In patients with coronary artery disease (CAD), HRQOL is compromised. Female patients with CAD have been reported to have lower HRQOL. In this study, we investigate gender differences in HRQOL and in associations of patient characteristics with HRQOL in patients with coronary angiography (CAG). Methods We cross-sectionally analysed patients from the Utrecht Coronary Biobank undergoing CAG. All patients filled in an HRQOL questionnaire (RAND-36 and EuroQoL) on inclusion. RAND-36 and EuroQoL HRQOL measures were compared between the genders across indications for CAG, CAD severity and treatment of CAD. RAND-36 HRQOL measures were compared with the general Dutch population. Additionally, we assessed interactions of gender with patient characteristics in their association with HRQOL (EuroQoL). Results We included 1421 patients (1020 men and 401 women) with a mean age of 65 in our analysis. Women reported lower HRQOL measures than men (mean EuroQoL self-rated health grade 6.84±1.49 in men, 6.46±1.40 in women, p<0.001). The reduction in RAND-36 HRQOL as compared with the general Dutch population was larger in women than in men. From regression analysis, we found that diabetes, a history of cardiovascular disease and symptoms of shortness of breath determined HRQOL (EuroQoL) more strongly in men than in women. Conclusions Women reported lower HRQOL than men throughout all indications for CAG and regardless of CAD severity or treatment. As compared with the general population, the reduction in HRQOL was more extreme in women than in men. Evident gender differences were found in determinants of HRQOL in patients undergoing CAG, which deserve attention in future research. Trial registration NCT02304744 (clinicaltrials.gov).

The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death worldwide and its prevalence is expected to rise rapidly worldwide in the coming decades. Atherosclerosis, the syndrome underlying CVD, is a chronic progressive disease of the arteries already present at a young age. Strokes, heart attacks and heart failure are acute CVD events that occur after decades, however, and require timely diagnosis and treatment. Plasma extracellular vesicles (EVs) are microstructures with a lipid bilayer membrane involved in hemostasis, inflammation and injury. Both EV-counts and EV-content are associated with CVD and the identification of plasma EVs is a novel source of blood-based biomarkers with the potential to improve diagnosis and prognosis of CVD. Presented in this review is an overview of the current use of EVs in CVD and a discussion of the need for robust and easy isolation technologies for plasma EV subsets. This is needed to bring this promising field towards clinical application in the patient.

Biomarkers of Coronary Artery Disease Differ Between Asians and Caucasians in the General Population

Coronary artery disease (CAD) markers have not been thoroughly investigated among Asians. The incidence of CAD, however, is rising rapidly in Asia. In this review, we systematically discuss publications that compare CAD biomarkers between Asians and Caucasians in the general population. A PubMed search yielded 5,570 hits, containing 59 articles describing 47 unique cohorts that directly compare Asians with Caucasians. Ten biomarkers were taken into account for this review: total cholesterol; triglycerides; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; C-reactive protein; glucose; insulin; glycated hemoglobin; fibrinogen; and plasminogen activator inhibitor-1. Triglycerides were 1.13-fold higher in South Asians than in Caucasians, and insulin levels were 1.33-fold higher. In Japanese and Chinese subjects, lower C-reactive protein levels were reported: 0.52 and 0.36-fold, respectively. Ethnicity-specific prognostic measures of CAD biomarkers were rarely reported. CAD biomarker levels differ between Asians and Caucasians and among Asian ethnic groups in population-based cohorts. The ethnicity-specific prognostic value of CAD biomarkers is yet to be determined.

Plasma extracellular vesicle protein content for diagnosis and prognosis of global cardiovascular disease

Cardiovascular disease is a major public health problem worldwide. Its growing burden is particularly ominous in Asia, due to increasing rates of major risk factors such as diabetes, obesity and smoking. There is an urgent need for early identification and treatment of individuals at risk of adverse cardiovascular events. Plasma extracellular vesicle proteins are novel biomarkers that have been shown to be useful in the diagnosis, risk stratification and prognostication of patients with cardiovascular disease. Ongoing parallel biobank initiatives in European (the Netherlands) and Asian (Singapore) populations offer a unique opportunity to validate these biomarkers in diverse ethnic groups.

AlluraClarity Radiation Dose-Reduction Technology in the Hybrid Operating Room During Endovascular Aneurysm Repair.

Purpose: To evaluate the effect of radiation dose reduction with the Allura ClarityIQ image processing technology for fixed C-arms in comparison with a mobile C-arm and an Allura fixed C-arm without ClarityIQ technology during endovascular aneurysm repair (EVAR) procedures. Methods: Radiation dose data from 85 patients (mean age 74.2±7.8 years; 68 men) undergoing EVAR with mobile and fixed C-arm fluoroscopy were retrospectively analyzed. The radiation dose parameters included the kerma area product (KAP), fluoroscopic time (FT), and number of digital subtraction angiography (DSA) frames (FrDSA). KAPtotal consisted of KAPfluoro (KAP for fluoroscopic imaging) and KAPDSA (KAP for DSA and single shots). Linear regression analysis was used to explore differences in the association of KAP with the FT, FrDSA, and body mass index (BMI) among the 3 C-arms. Results: The mean KAPtotal values for mobile, Allura C-arm, and AlluraClarity C-arm for noncomplex EVARs were 56±39, 245±142, and 157±120 Gy·cm2 (p<0.001); for complex EVARs, the values were 110±43, 874±653, and 598±319 Gy·cm2 (p<0.001), respectively. On average, KAPfluoro tripled when the mobile C-arm was replaced by the fixed C-arm. There were no significant differences in the KAPfluoro adjusted for the FT between Allura and AlluraClarity (p=0.69). However, there was a major 61% reduction in KAPDSA from 1.36 Gy·cm2 per DSA frame for Allura to 0.54 Gy·cm2 per DSA frame with AlluraClarity (p=0.03). For the mobile C-arm, BMI was not associated with KAP (p=0.13). The associations of BMI with KAPfluoro and KAPDSA were significant for both fixed C-arms but were more robust for Allura compared to AlluraClarity (p=0.02 for KAPfluoro and p<0.001 for KAPDSA). Conclusion: Changing a mobile C-arm for a fixed C-arm in a hybrid operating suite increased the average intraoperative dose during EVAR. Upgrading the Allura fixed C-arm with ClarityIQ technology resulted in a 61% reduction in the radiation per DSA frame.

Ethnicity Modifies Associations between Cardiovascular Risk Factors and Disease Severity in Parallel Dutch and Singapore Coronary Cohorts.

Background In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world’s most populous ethnicities: Whites, Chinese, Indians and Malays. Methods The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. Results We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1–1.7], p = 0.008) and Malay (OR 1.9 [1.4–2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. Conclusion In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality.

Hematological Parameters Improve Prediction of Mortality and Secondary Adverse Events in Coronary Angiography Patients : A Longitudinal Cohort Study

AbstractPrediction of primary cardiovascular events has been thoroughly investigated since the landmark Framingham risk score was introduced. However, prediction of secondary events after initial events of coronary artery disease (CAD) poses a new challenge.In a cohort of coronary angiography patients (n = 1760), we examined readily available hematological parameters from the UPOD (Utrecht Patient Oriented Database) and their addition to prediction of secondary cardiovascular events. Backward stepwise multivariable Cox regression analysis was used to test their ability to predict death and major adverse cardiovascular events (MACE). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) measures were calculated for the hematological parameters on top of traditional risk factors to assess prediction improvement.Panels of 3 to 8 hematological parameters significantly improved prediction of death and adverse events. The IDIs ranged from 0.02 to 0.07 (all P < 0.001) among outcome measures and the cNRIs from 0.11 to 0.40 (P < 0.001 in 5 of 6 outcome measures). In the hematological panels red cell distribution width (RDW) appeared most often. The multivariable adjusted hazard ratio of RDW per 1 standard deviation (SD) increase for MACE was 1.19 [1.08–1.32], P < 0.001.Routinely measured hematological parameters significantly improved prediction of mortality and adverse events in coronary angiography patients. Accurately indicating high-risk patients is of paramount importance in clinical decision-making.

Routinely analyzed leukocyte characteristics improve prediction of mortality after coronary angiography

Background Inflammation and leukocyte infiltration are hallmarks of atherosclerosis. Clinically routine hematology analyzers mostly perform an entire differential blood count by default, irrespective of the requested parameter. We hypothesize that these normally unreported leukocyte characteristics associate with coronary artery disease (CAD) severity and can improve prediction of mortality in coronary angiography patients. Methods We studied coronary angiography patients suspected of CAD (n = 1015) from the Utrecht Coronary Biobank cohort. Leukocyte characteristics were routinely assessed in blood drawn directly prior to angiography using an automated hematology analyzer and extracted from the Utrecht patient oriented database (UPOD) database. Patients were followed up for a median duration of 805 days, during which 65 patients died. We evaluated the association of leukocyte characteristics with synergy between PCI with taxus and cardiac surgery (SYNTAX) score as a measure of CAD severity, all-cause and cardiovascular mortality and major adverse cardiovascular events (MACEs). In order to determine the improvement of risk prediction, we calculated continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI). Results Monocyte percentage showed strong independent predictive value for all-cause mortality (hazard ratio (HR) 1.44 (1.19–1.74), p < 0.001), and the monocyte-to-lymphocyte ratio performed best for cardiovascular mortality (HR 1.42 (1.11–1.81), p = 0.005). The cNRIs and IDIs of leukocyte characteristics for all-cause mortality confirmed the improvement in mortality risk prediction. No significantly predictive leukocyte characteristics were found for MACEs. Conclusion Readily available yet unreported leukocyte characteristics from routine hematology analyzers significantly improved prediction of mortality in coronary angiography patients on top of clinical characteristics.

Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure

Background QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. Methods We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. Results Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. Conclusion We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.