Anath Oren

Carotid intima-media thickness, arterial stiffness and risk of cardiovascular disease: current evidence

Aims Over recent decades the interest in cardiovascular epidemiology has broadened from studies on causes and consequences of elevated cardiovascular risk factors to include research on causes and consequences of atherosclerosis and associated arterial wall abnormalities. One of the underlying reasons was that established cardiovascular risk factors were insufficiently accurate in identifying those individuals who will suffer from cardiovascular disease in the future and measures of subclinical atherosclerosis may enhance the precision of these predictions and thus enable better-tailored medical care to be provided. The usefulness of measuring subclinical atherosclerosis is conditional on evidence that presence of subclinical atherosclerosis confers an increased risk of cardiovascular disease and that favourable changes in subclinical atherosclerosis parallel reductions in risk. We aimed at providing an overview of epidemiological data on carotid intima–media thickness (CIMT) and arterial stiffness measurements and their relation to risk of cardiovascular disease. Methods We reviewed the published epidemiological data. Results and conclusion CIMT is a good indicator of cardiovascular risk and provides a graded measure of vascular damage: no clear CIMT level above which the cardiovascular risk appears to increase considerably. The evidence for arterial stiffness, assessed as carotid distensibility or aortic pulse wave velocity, as an indicator for risk of cardiovascular disease is restricted to subjects with either hypertension or end-stage renal disease or based on small studies in renal transplant patients and elderly. Evidence to indicate that information on carotid intima–media thickness or arterial stiffness, additional to established cardiovascular risk factors, helps to distinguish subjects into those with a high and those with a low absolute risk of cardiovascular disease is limited, but needed. Also, information on the direct comparison of both arterial stiffness measures in their ability to predict cardiovascular disease is needed.

Gestational age and birth weight in relation to aortic stiffness in healthy young adults: two separate mechanisms?*

BACKGROUND Impaired vascular development due to intrauterine growth retardation and postnatal-induced vascular damage by an unfavorable cardiovascular risk profile may both cause stiffer arteries in later decades. METHODS Of 524 young adults, participating in the Atherosclerosis Risk in Young Adults (ARYA) study, data on birth characteristics were obtained from the original medical records of the Municipal Health Service and the extent of aortic stiffness was assessed using carotid-femoral pulse wave velocity (PWV). RESULTS The PWV showed an inverse trend with gestational age (linear regression coefficient (beta) = -0.07 m/sec per 1 week; P =.064) whereas it was positively related to birth weight (beta = 0.33 m/sec per 1 kg; P =.020), adjusted for blood pressure (BP), gender, age, and each other. After exclusion of the 26 prematurely born infants, the association with gestational age was attenuated (beta = -0.03 m/sec per 1 week; P =.582), whereas the relation with birth weight hardly changed (beta = 0.30 m/sec per 1 kg; P =.041). In an analysis in which we excluded the 26 subjects with diabetic mothers the birth weight-PWV relation was attenuated (beta = 0.21 m/sec per 1 kg; P =.169). CONCLUSIONS Our findings suggest that prematurity drives the relation of gestational age and PWV, whereas risk of impaired glucose tolerance drives the relation of birth weight and PWV. We hypothesized that two separate mechanisms might be involved in the development of arterial stiffness in healthy young adults.

Aortic stiffness and carotid intima-media thickness: two independent markers of subclinical vascular damage in young adults?

Background  Previous reports have shown that carotid intima‐media thickness (CIMT) and arterial stiffness are strong predictors of subsequent cardiovascular disease (CVD) morbidity and mortality, and are well related to an unfavourable cardiovascular risk profile in middle‐aged and older subjects. These similarities suggest that arterial stiffness may play a role in the development of atherosclerosis or vice versa. However, studies show conflicting results and are limited to elderly subjects. To study this issue further, we evaluated the relation of arterial stiffness to subclinical atherosclerosis in 524 healthy young adults, aged 27–30 years.

Adolescent blood pressure and blood pressure tracking into young adulthood are related to subclinical atherosclerosis: the Atherosclerosis Risk in Young Adults (ARYA) study

BACKGROUND Increased blood pressure (BP) in young adulthood is associated with cardiovascular morbidity and mortality. Longitudinal studies of patients at young ages are, however, limited. Our aim was to study the relationships of adolescent BP and tracking of BP into young adulthood with subclinical atherosclerosis, as assessed by carotid intima-media thickness (CIMT), at the age of 28 years. METHODS The Atherosclerosis Risk in Young Adults (ARYA) study comprises of a community-based sample of 750 subjects aged 27 to 30 years. In the 352 men and 398 women, at least one BP measurement was recorded at a mean age of 13 years in school health records. Recently, all participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasound examination of both common carotid arteries to assess CIMT. RESULTS Linear regression showed that adolescent systolic BP was associated with thickening of the intima-media (an increase of 7.5 microm in CIMT per standard deviation increase in systolic BP; 95% CI 4.3 to 10.6). Similar relations were found for pulse pressure and mean arterial pressure. When sex, age, and body mass index at adolescence and young adulthood and adult BP were taken into account, the relations attenuated, but for pulse pressure they remained statistically significant. Furthermore, subjects who tracked in the highest systolic BP and pulse pressure levels from adolescence into young adulthood showed the thickest CIMT. CONCLUSION Our findings strengthen the notion that elevated BP at adolescence and a relative increase in BP from adolescence to adulthood unfavorably affect cardiovascular risk, as indicated by increased CIMT.

Birth weight and carotid intima-media thickness: new perspectives from the atherosclerosis risk in young adults (ARYA) study

PURPOSE Although intrauterine growth retardation (IUGR) is associated with increased risk of cardiovascular disease (CVD) in adult life, it is unclear whether the relationship is present at younger ages. Furthermore, current debate suggests that postnatal factors might be at least as important as prenatal conditions. The authors investigated whether low birth weight leads to an increased risk of subclinical atherosclerosis in a population-based sample of 750 Dutch men and women, aged 27 to 30 years. METHODS Information about birth characteristics was available from the original charts of the Municipal Health Service, Utrecht, The Netherlands. Cardiovascular risk factors were evaluated by a questionnaire. The extent of atherosclerosis, assessed by carotid intima-media thickness (CIMT), was measured in both common carotid arteries. RESULTS Overall, birth weight was not related to common CIMT. However, in the lowest tertile of birth length an inverse association between birth weight and common CIMT was observed. Moreover, low birth weight was significantly associated with increased common CIMT in those who showed exaggerated postnatal growth. CONCLUSIONS These findings suggest that low birth weight is only associated with increased common CIMT in young adulthood in those who experienced severe IUGR and in those who showed exaggerated postnatal growth.

Spurious systolic hypertension in young adults; prevalence of high brachial systolic blood pressure and low central pressure and its determinants.

Objective To investigate the prevalence and determinants of spurious systolic hypertension (SSH) in a population-based sample of young adults and estimate their 20-year risk of coronary heart disease. Population and methods Seven hundred and fifty young adults (352 men and 398 women), aged 26–31 years, from the Atherosclerosis Risk in Young Adults study were studied. Blood pressure levels were measured twice and central (aortic) pressures were derived by applanation tonometry on the radial artery using a generalized transfer function. SSH was defined as brachial systolic blood pressure (SBP) ≥ 140 mmHg, brachial diastolic blood pressure (DBP) < 90 mmHg, and central SBP < 124 mmHg for men and < 120 mmHg for women. The Framingham risk score was calculated. Analysis of variance models were used to compare SSH individuals with normotensive and hypertensive males for cardiovascular risk factors. Results SSH was diagnosed in 57 men (16.1%; 95% confidence interval, 12.3–20.0) versus only three women (8%; 95% confidence interval, 0–1.6). The female population was excluded from further analysis. Compared with normotensive males, SSH individuals were heavier (88.7 versus 81.8 kg, P < 0.05) had a higher body mass index (25.8 versus 24.2 kg/m2, P < 0.01) and significantly higher brachial and central SBP, DBP, pulse pressure, and mean arterial pressure. They had significantly higher pulse pressure amplification. Twenty-year Framingham risk scores based on DBP did not differ significantly between SSH subjects and normotensive individuals (2.72 versus 2.10%, respectively). Conclusion SSH is predominantly found among young adult men. Apart from weight and body mass index, no other cardiovascular risk factors differed significantly between subjects with SSH and normotension or hypertension. When calculating the 20-year risk of coronary heart disease based on brachial DBP, SSH individuals were at intermediate risk between normotensive and hypertensive participants, but differences were not statistically significant.

Determinants of augmentation index in young men: The ARYA study

Background  There is an increasing interest in the augmentation index (AIx), the proportion of the central pulse pressure resulting from peripheral arterial wave reflection, which has been related to cardiovascular disease risk and mortality. Most of the data on the AIx have been collected in patients with established cardiovascular disease. In contrast, data in the young are scarce. However, as AIx might be used to evaluate cardiovascular disease risk already at an early age, we aimed to study determinants of AIx in a population of healthy young men.

The Atherosclerosis Risk in Young Adults (ARYA) study: rationale and design.

Introduction: Despite recent advances in treatment, cardiovascular disease (CVD) is still health problem number one in western societies. Aiming at specific prevention strategies for high-risk individuals and shifting the available prevention programs towards younger age groups might increase the success of primary prevention. However, before addressing age-specific prevention programs, more insight in the determinants of early vascular damage and increased cardiovascular risk is warranted as well as insight in determinants increased cardiovascular risk, including vascular damage, at an early age. The Atherosclerosis Risk in Young Adults (ARYA) study was specifically designed to address this issue. Objectives: The ARYA study started off with studies evaluating (1) whether it is possible to predict cardiovascular risk at young adulthood by routinely measured adolescent data, and (2) evaluating the role of birth characteristics and adolescent characteristics to the development of vascular damage at young adulthood. Methods: The ARYA study comprises of two cohorts of young adults. The Utrecht cohort includes 750 young adults, aged 27–30 years. The Hague-cohort includes 261 young adults born between 1963 and 1968. Data on birth characteristics, growth in early infancy as well as adolescent anthropometry, blood pressure, lipids, body mass index were obtained from the original medical records of the Municipal Health Service. In 1999/2001, the extent of subclinical vascular damage was measured using carotid wall thickness and aortic stiffness. Also, data on adult cardiovascular risk profile, bone density and central blood pressure were assessed, fasting blood was drawn and timed overnight urine samples were collected. Conclusion: The ARYA study is aimed to provide data on early determinants of cardiovascular risk, including vascular damage, at an early age. This knowledge enhances the understanding of atherosclerosis development and CVD risk and is needed to improve the available primary prevention programs.