Karlijn A. Groenewegen

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.

Vascular age to determine cardiovascular disease risk: A systematic review of its concepts, definitions, and clinical applications

Background Vascular age is an alternate means of representing an individuals cardiovascular risk. Little consensus exists on what vascular age represents and its clinical utility has not been determined. We systematically reviewed the literature to provide a comprehensive overview of different methods that have been used to define vascular age, and to examine its potential clinical value in patient communication and risk prediction. Design This was a systematic review with data sources of PubMed and Embase. Results We identified 39 articles on vascular age, 20 proposed to use vascular age as a communication tool and 19 proposed to use vascular age as a means to improve cardiovascular risk prediction. Eight papers were methodological and 31 papers reported on vascular age in study populations. Of these 31 papers, vascular age was a direct translation of the absolute risk estimated by existing cardiovascular risk prediction models in 15 papers, 12 derived vascular age from the reference values of an additional test, and in three papers vascular age was defined as the age at which the estimated cardiovascular risk equals the risk from non-invasive imaging observed degree of atherosclerosis. One trial found a small effect on risk factor levels when vascular age was communicated instead of cardiovascular risk. Conclusion Despite sharing a common name, various studies have proposed distinct ways to define and measure vascular age. Studies into the effects of vascular age as a tool to improve cardiovascular risk prediction or patient communication are scarce but will be required before its clinical use can be justified.

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.

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.

The impact of variability in ultrasound settings on the measured echolucency of the carotid intima-media

Background: B-mode ultrasound measurements of the echolucency of the carotid intima–media may hold information on cardiovascular risk. The information obtained from this measurement may depend on which gain settings are used. We studied the effect of gain settings on echolucency measurements and its consequences on risk factor relations and treatment effects. Methods: We used two approaches. In the first, we examined the relationship between calibration, gain and common grey-scale median (GSM) from repeated ultrasound images obtained from four healthy individuals at gain settings ranging from −20 to 20 dB. In the second, we evaluated the effect of gain settings on the relation of risk factors and statin treatment with common GSM, using images from 325 participants of the Measuring Effects on Intima–Media Thickness: an Evaluation of Rosuvastatin (METEOR) study with documented gain settings. Echolucency of the carotid intima–media was measured from ultrasound images using PaintShop Pro and Artery Measurement Software and expressed as GSM. Results: In healthy individuals, common GSM increased with increments in gain setting, primarily when the measurements were not calibrated. In the METEOR study sample, age and sex were significantly related to gain setting. The risk factor relations with common GSM were of the same magnitude and direction after adjustment for gain setting. Furthermore, adjustment for gain setting did not alter the rates of GSM change over time. Conclusion: Extreme variability in gain settings has a major impact on the echolucency measurements of the far wall common carotid intima–media. Calibration should be used to adjust for these effects of gain settings. Variability in gain settings, however, seems limited in real practice and did not change the direction and magnitude of the relations under study. However, as age and sex are major determinants of gain settings, adjustment for or stratification by age and sex is recommended in studies into echolucency of the carotid intima–media in situations in which gain settings are unknown.

Common Carotid Intima-Media Thickness Measurements Do Not Improve Cardiovascular Risk Prediction in Individuals With Elevated Blood Pressure

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.

Relation Between Adolescent Cardiovascular Risk Factors and Carotid Intima-Media Echogenicity in Healthy Young Adults: The Atherosclerosis Risk in Young Adults (ARYA) Study.

Background Echogenicity is an ultrasound measure that reflects arterial wall composition. In adult populations, lower carotid intima‐media echogenicity relates to an unfavorable cardiovascular risk burden yet appears to reflect a different aspect of arterial wall remodeling than carotid intima‐media thickness (CIMT). Since studies on carotid intima‐media echogenicity earlier in life are lacking, we investigated associations between adolescent cardiovascular risk factors and young adulthood carotid intima‐media echogenicity and compared this to CIMT. Methods and Results In 736 participants of the Atherosclerosis Risk in Young Adults study, information on adolescent anthropometrics, puberty stage, and systolic blood pressure (SBP) was available. In young adulthood, demographics, anthropometrics, and fasting plasma samples were collected. Common CIMT and echogenicity, quantified as gray‐scale median (GSM), were evaluated using B‐mode ultrasonography. Lower and higher GSM values, respectively, represented lower and higher echogenicity. Associations of adolescent body mass index and SBP with young adulthood GSM and CIMT were evaluated using linear regression analysis. Mean age was 13.5 years in adolescence and 28.4 years in young adulthood (difference: 14.9 years). After full adjustment, adolescent body mass index related to GSM (β=−1.62/SD; 95% CI: −2.79, −0.46; P=0.006), independent of CIMT. Adolescent SBP did not relate to GSM. Moreover, adolescent body mass index (β=8.06 μm/SD [95% CI: 4.12, 11.99], P<0.001) and SBP (β=4.69 μm/SD [95% CI: 0.84, 8.54], P=0.02) related to CIMT. Conclusions Adolescent body mass index related to GSM and CIMT in young adulthood; SBP only related to CIMT. Hence, carotid intima‐media echogenicity appears to be involved in arterial wall remodeling, yet may mimic a different facet of this process than CIMT.

The Influence of a Sudden Increase in Playing Time on Playing-Related Musculoskeletal Complaints in High-Level Amateur Musicians in a Longitudinal Cohort Study

Background Several studies in the domain of professional musicians describe the relation between playing time and the occurrence of musculoskeletal complaints in professional musicians. To date, no longitudinal cohort study into this relationship has been performed and no amateur musicians were studied. Therefore, the aim of this study is to examine the causal relationship between a sudden increase in playing time among amateur musicians on the occurrence of musculoskeletal complaints in a prospective cohort study. Methods All members of two national Dutch Students Orchestras were asked to participate in the study. These project-based orchestras, consisting of high-level amateurs, followed a nine-hour rehearsing schedule for ten consecutive days. On the first day (t0) and after one week (t1) the subjects were asked to complete a paper-based questionnaire including sociodemographic characteristics, music-related questions, questions regarding playing-related musculoskeletal complaints and the music module of the disabilities of arm, shoulder and hand questionnaire. Results The NSO consisted of 85 and the NESKO of 41 members during the study period. 59 subjects completed the questionnaire at both timepoints (response rate 47%). 9 subjects were excluded for being a music academy student, leaving 50 subjects (mean age 22.1, 72% female) suitable for analysis. During the rehearsal week, the prevalence of at least one playing-related musculoskeletal complaint increased from 28% to 80%. The most frequently affected areas were the neck, upper and lower back, hand/and or wrists and shoulders. The DASH music module score increased from 14 at t0 to 23 at t1. Conclusion A point prevalence of 28% at the start of the study that increased remarkably to 80% within a one-week period. Future research should evaluate other risk factors for musculoskeletal complaints in amateur musicians. These risk factors should be the base for the development of preventive measures.

The high prevalence of playing-related musculoskeletal disorders (PRMDs) and its associated factors in amateur musicians playing in student orchestras: A cross-sectional study

Objective Despite the high number of amateur musicians in the general population, little is known about the musculoskeletal health of amateur musicians. Playing a musical instrument is supposed to be a risk factor for the development of musculoskeletal complaints. This study aimed to evaluate playing-related musculoskeletal disorders (PRMDs) among amateur musicians playing in student orchestras. Design A cross-sectional study. Participants 357 members of eleven Dutch student orchestras across the Netherlands were included in this study. Intervention A paper-based questionnaire on PRMDs was used. Outcome measures Sociodemographic characteristics and PRMDs were evaluated using an adaptation of the Nordic Musculoskeletal Questionnaire (NMQ) and the music module of the Disabilities of Shoulder and Hand (DASH) questionnaire. Results The year prevalence of PRMDs among amateur musicians was 67.8%. Female gender, younger age, higher BMI and playing a string instrument were independently associated with a higher prevalence of PRMDs. The left shoulder was affected more frequently in violinists and violists, whereas the right hand and wrist were more frequently affected in woodwind instrumentalists. Of the subjects with PRMDs during the last week, the score of the music module of the DASH was 18.8 (6.3–31.2) Discussion This study is the first to report on PRMDs and its associated factors in a large group of amateur musicians. The prevalence of PRMDs in amateur musicians is high, however the DASH scores reflect a confined impact of these PRMDs on their functioning as a musician. Preventive measures are needed aiming at reducing PRMDs among amateur musicians.

Common Carotid Intima-Media Thickness Measurements Do Not Improve Cardiovascular Risk Prediction in Individuals With Elevated Blood PressureNovelty and Significance

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.