Suzanne Holewijn

Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction: A Meta-analysis

CONTEXT The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. OBJECTIVE To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. DATA SOURCES Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. STUDY SELECTION Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. DATA EXTRACTION Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. RESULTS We included 14 population-based cohorts contributing data for 45,828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. CONCLUSION The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.

Inflammation in deep vein thrombosis and the development of post‐thrombotic syndrome: a prospective study

Summary.  Background: The aim of this study was to investigate whether inflammatory markers (interleukin‐6 [IL‐6] and C‐reactive protein [CRP]) in the acute phase of deep vein thrombosis (DVT) are associated with elevated venous outflow resistance (VOR), thrombosis score (TS), reflux and the development of clinical post‐thrombotic syndrome (PTS). Methods: In 110 patients with a first DVT, plasma concentrations of IL‐6 and CRP were determined on the day of admission. VOR, TS and reflux were measured 7 days, 1 and 3 months after diagnosis. After 1 year patients were evaluated for PTS using the Clinical, Etiologic, Anatomic and Pathophysiologic (CEAP) classification and Villalta scale. Results: Median levels of IL‐6 and CRP were 7 pg mL−1 and 21 mg L−1, respectively. After 3 months, VOR was elevated in 33 patients (30%), TS in 33 (30%) and reflux in 57 (52%). Incidence of PTS was 36.7% using CEAP ≥ 3 and 35.4% using Villalta‐scale ≥ 5. Elevated levels of IL‐6 and CRP were related to higher outcomes of VOR after 3 months [relative risks (RR) 2.4 (95% CI 1.5–3.9) and 1.4 (1.1–3.3), respectively] and for IL‐6 to TS [1.5 (1.1–2.1)]. For reflux no relation was found. After 90 days, elevated outcomes of VOR, TS and reflux were related to PTS after 1 year. The association of IL‐6 and CRP with PTS was weak using the CEAP classification with a RR of 1.2 (0.7–2.2) and 1.8 (0.9–3.3) and absent according to the Villalta scale 0.6 (0.2–1.4) and 1.2 (0.6–2.5), respectively. Conclusion: The results of this study suggest that inflammation might play a role in incomplete thrombus clearance, venous outflow obstruction and the development of PTS after 1 year.

The Metabolic Syndrome and Its Traits as Risk Factors for Subclinical Atherosclerosis

CONTEXT AND OBJECTIVE The metabolic syndrome (MetS) indicates an increased cardiovascular risk. The objective of the present study was to determine the impact of the MetS and its individual traits on subclinical atherosclerosis, as measured with six noninvasive measurements of atherosclerosis (NIMA) in a 50- to 70-yr-old Dutch population-based cohort. Furthermore, we determined the impact of three different definitions of the MetS. DESIGN We performed NIMA in 1517 participants of the Nijmegen Biomedical Study. The MetS was defined by definitions of the National Cholesterol Education Program, International Diabetes Federation, and the World Health Organization. RESULTS Participants with the MetS (National Cholesterol Education Program) were characterized by increased subclinical atherosclerosis compared with participants without any trait of the MetS, as reflected by lower ankle-brachial index at rest [percent change (95% confidence interval), M: -5.2% (-9; -1), F: -3.1% (-6; -1)] and after exercise [M: -7.7% (-17;+2), F: -6.6% (-11; -2)], higher augmentation index [M: +4.8% (+3; +7), F: +1.9% (+4; +18)], increased pulse wave velocity [M: +22.8% (+15;+32), F: +20.5% (+14; +28)], increased intima-media thickness [M: +9.3% (+5; +13), F: +6.9% (+3; +11)], and thicker plaques [M: +17.6% (-2; +41), F: +26.6% (+5; +53)]. Most intriguingly, the number of traits was strongly associated with the severity of subclinical atherosclerosis because all NIMA gradually deteriorated with increasing number of traits present; NIMA were already deteriorated when one or two traits were present and further deteriorated when four or five traits of the MetS were present. Similar result were found when International Diabetes Federation and World Health Organization definitions of the MetS were used. CONCLUSIONS For cardiovascular risk prediction, it is more important to take into account the presence of each individual trait and the number of traits of the MetS than to diagnose the presence of the MetS.

Endovenous mechanochemical ablation of great saphenous vein incompetence using the ClariVein device: a safety study.

Purpose To evaluate the feasibility and safety of endovenous mechanochemical ablation (MOCA) for the treatment of great saphenous vein (GSV) incompetence. Methods The newly developed ClariVein device uses a technique that combines mechanical endothelial damage using a rotating wire with the infusion of a liquid sclerosant. Heating of the vein and tumescent anesthesia are not required; only local anesthesia is utilized at the insertion site. In a pilot study, 30 limbs in 25 patients (18 women; mean age 52 years) with GSV incompetence were treated with MOCA using polidocanol at 2 centers. Initial technical success, complications, patient satisfaction, and classification by venous clinical severity score (VCSS) were assessed 6 weeks after the treatment. Results Initial technical success of MOCA was 100%. There were no major adverse events. Minor complications consisted of 9 local ecchymoses at the puncture site and superficial phlebitis that resolved within a week in 4 limbs. Duplex ultrasonography at 6 weeks showed 26 (87%) of 30 veins were completely occluded; 3 veins showed partial recanalization in the proximal (n=2) and distal GSV. One patient had full segment recanalization and was successfully retreated. The VCSS significantly improved at 6 weeks (p<0.001). Patient satisfaction was high, with a median satisfaction of 8.8 on a 0–10 scale. Conclusion This study showed that endovenous MOCA, using polidocanol, is feasible and safe in the treatment of GSV incompetence. Larger studies with a prolonged follow-up are indicated to prove the efficacy of this technique in terms of obliteration rates.

Variation in non-invasive measurements of vascular function in healthy volunteers during daytime.

Although it is often recommended to standardize the time of day when performing non-invasive measurements of vascular function, the exact influence of the time of day on the outcome of IMT (intima-media thickness), PWV (pulse wave velocity), AIX (augmentation index) and FMD (flow-mediated dilatation) measurements has not been reported before. Nineteen healthy volunteers visited our department on two different occasions: the first visit was at 09:00 hours after an overnight fast, and the second visit was at 14:00 hours after a standardized breakfast. Non-invasive measurements of atherosclerosis were performed twice at 09:00 hours and once on the second visit at 14:00 hours. Measurement of IMT, PWV, AIX and FMD was reproducible according to the method of Bland and Altman. The absolute difference between repeated measurements at 09:00 hours showed no significant difference compared with the absolute difference between 09:00 and 14:00 hours for IMT (0.029+/-0.014 compared with 0.021+/-0.014 mm; P = 0.27), PWV (0.63+/-0.50 compared with 0.75+/-0.74 m/s; P = 0.52), AIX (4.0+/-4.0 compared with 5.5+/-5.2%; P = 0.35) and FMD (3.8+/-3.7 compared with 4.2+/-2.9%; P = 0.70). In conclusion, our results show that, in healthy volunteers during the daytime, IMT, PWV, AIX and FMD outcomes are not confounded by variation in the exact time of the examination as long as other (exogenous) conditions, including food intake, smoking and intake of alcohol, are carefully controlled for.

Depressive Symptom Clusters Are Differentially Associated with General and Visceral Obesity

OBJECTIVES: To examine the relationship between obesity and depressive symptoms taking into account different measures for obesity (body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR)) and different depressive symptom clusters.

Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk

Abstract.  Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AFH, de Graaf J. (Address: Division of Vascular Medicine, Department of General Internal Medicine; Department of Epidemiology and Biostatistics; Department of Endocrinology; and Department of Laboratory Medicine; Laboratory of Clinical Chemistry, all at the Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands) Apolipoprotein B, non‐HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk. J Intern Med 2010; 268: 567–577.

Brachial artery diameter is related to cardiovascular risk factors and intima-media thickness

Background  Previous reports showed inconsistent results about the potential role of flow‐mediated dilatation (FMD) in cardiovascular(CV) risk prediction. Few data are available about the role of nitroglycerin‐mediated dilatation (NMD), but recently, brachial artery diameter(BAD) appeared to have predictive value in CV risk prediction.We determined the relation of FMD, BAD and NMD with known CV risk factors and intima‐media thickness (IMT), a well‐established surrogate marker of atherosclerosis, in a community‐based population, the Nijmegen Biomedical Study (NBS).

Common Carotid Intima-Media Thickness Measurements Do Not Improve Cardiovascular Risk Prediction in Individuals With Elevated Blood Pressure: The USE-IMT Collaboration

Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (ie, a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, −1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6–10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant.

Common Carotid Intima-Media Thickness Relates to Cardiovascular Events in Adults Aged <45 Years

Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population–based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11–1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden.