M.L. Bots

Endogenous Sex Hormones and Progression of Carotid Atherosclerosis in Elderly Men

Background—The burden of atherosclerosis especially afflicts the increasing older segment of the population. Recent evidence has emphasized a protective role of endogenous sex hormones in the development of atherosclerosis in aging men. Methods and Results—We studied the association between endogenous sex hormones and progression of atherosclerosis in 195 independently living elderly men. Participants underwent measurements of carotid intima-media thickness (IMT) at baseline in 1996 and again in 2000. At baseline, serum concentrations of testosterone (total and free) and estradiol (total and free E2) were measured. Serum free testosterone concentrations were inversely related to the mean progression of IMT of the common carotid artery after adjustment for age (β=−3.57; 95% CI, −6.34 to −0.80). Higher serum total and free E2 levels were related to progression of IMT of the common carotid artery after adjustment for age (β=0.38; 95% CI, −0.11 to 0.86; and β=0.018; 95% CI, −0.002 to 0.038, respectively). These associations were independent of body mass index, waist-to-hip ratio, presence of hypertension and diabetes, smoking, and serum cholesterol levels Conclusions—Low free testosterone levels were related to IMT of the common carotid artery in elderly men independently of cardiovascular risk factors.

Risk Factors for Progression of Atherosclerosis Measured at Multiple Sites in the Arterial Tree: The Rotterdam Study

Background and Purpose— Studies investigating determinants of atherosclerotic disease progression are relatively rare. Moreover, although atherosclerotic disease can be assessed noninvasively in different vascular beds, previous studies have not considered progression of atherosclerosis at >1 site. The present study was designed to identify risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree. Methods— The Rotterdam Study is a population-based cohort study of 7983 men and women ≥55 years of age. Carotid plaques and intima-media thickness were assessed by ultrasound, aortic atherosclerosis by x-ray, and lower-extremity atherosclerosis by the ankle-arm index. Data on progression of atherosclerosis over an average period of 6.5 years were available for 3409 participants. Associations of established cardiovascular risk factors with mild, moderate, and severe progression of atherosclerosis were investigated through multinomial regression analysis. Results— Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension were strong, independent predictors of moderate and severe progression of atherosclerosis at multiple sites. Diabetes mellitus predicted only severe progression of atherosclerosis. Associations of sex with progression of atherosclerosis were remarkably modest. Conclusions— Age, smoking, total cholesterol, and systolic blood pressure and/or hypertension strongly predict progression of extracoronary atherosclerosis in the elderly, but sex remarkably does not. These results emphasize the need for prevention of progression of extracoronary atherosclerotic disease in men and women alike.

Alcohol consumption and arterial stiffness in men

Objective Moderate alcohol consumption has been proposed to be anti-atherogenic and protect against coronary heart disease. Arterial stiffness provides a summary measure of atherosclerotic arterial damage and cardiovascular risk. A vascular protective effect of moderate alcohol consumption would be reflected in an inverse association between alcohol intake and aortic stiffness. Design A cross-sectional study. Setting The male population of Utrecht. Participants Of 370 men, aged 40–80 years, alcohol intake was calculated from a standardized questionnaire and aortic stiffness was non-invasively assessed by pulse-wave velocity (PWV) measurement of the aorta. Results There were no non-drinkers; therefore the group consuming 0–3 glasses of alcoholic beverage per week was chosen as the reference group in the analyses. Those drinking 4–10, 11–21 and 22–58 glasses of alcoholic beverage per week had a −0.77 m/s (95% confidence interval, −1.26 to −0.28), −0.57 m/s (95% confidence interval, −1.07 to −0.08) and −0.14 m/s (95% confidence interval, −0.65 to 0.36) difference in mean PWV compared with those drinking 0–3 glasses per week. Adjustment for factors that correlated with PWV or alcohol consumption did not change the strength of the association. Conclusion Among men aged 40–80 years there is a J-shaped association between alcohol consumption and PWV. This further supports a decreased risk of cardiovascular disease with moderate alcohol consumption.

Common carotid intima-media thickness in patients with peripheral arterial disease or abdominal aortic aneurysm: the SMART study

Evidence is emerging that the contribution of atherosclerosis to the development of abdominal aortic aneurysm may differ from that of other manifestations of arterial disease. B-mode ultrasound may be helpful in understanding the characteristics and factors that contribute to the development of different manifestations of arterial disease. We examined whether there is a difference in common carotid intima-media thickness (IMT), an indicator of generalized atherosclerosis, in patients with peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA). IMT of the left and right common carotid artery was measured in the first 172 patients (123 PAD and 49 AAA) enrolled in the Second Manifestations of ARTerial disease (SMART) study, a cohort study among patients with a manifestation of atherosclerotic vascular disease or risk factors for atherosclerosis. Mean IMT was 0.98 +/- 0.34 mm in patients with PAD and 0.91 +/- 0.20 mm in patients with AAA, with an age and sex adjusted mean difference of 0.18 mm (95% CI 0.08; 0.28). After additional adjustments for cardiovascular risk factors, the difference remained 0.11 mm (95% Cl 0.01; 0.21). Common carotid IMT in patients with AAA is on average smaller than in patients with PAD, independent of other determinants of IMT. These findings support the view that the development of AAA cannot completely be explained by atherosclerosis and is in part due to other pathophysiological mechanisms.

Treatment with hormone replacement therapy lowers remnant lipoprotein particles in healthy postmenopausal women: results from a randomized trial

Background Recent evidence indicates that remnant lipoprotein particles (RLPs) may play a role in atherosclerosis. Remnant lipoprotein particles have been suggested to be the most atherogenic particles among the triglyceride‐rich lipoproteins. In particular, these triglyceride‐rich particles were identified as an independent risk factor for cardiovascular diseases (CVD) in women. Postmenopausal hormone replacement therapy (HRT) beneficially affects lipid profile, although total triglyceride levels often increase. Evidence on the effects of HRT on RLPs is limited. We determined whether 3 months’ treatment of postmenopausal women with Tibolone or conjugated oestrogens combined with medroxyprogesterone acetate (CEE + MPA) affects RLP‐cholesterol (RLP‐C).

Early mitral valve repair versus watchful waiting in patients with severe asymptomatic organic mitral regurgitation; rationale and design of the Dutch AMR trial, a multicenter, randomised trial

BackgroundAsymptomatic severe mitral valve (MV) regurgitation with preserved left ventricular function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting. For asymptomatic patients, no randomised trial has been performed for objectivising the best treatment strategy.MethodsThe Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation. A total of 250 asymptomatic patients (18–70xa0years) with preserved left ventricular function will be included. Intervention will be either watchful waiting or MV surgery. Follow-up will be 5xa0years. Primary outcome measures are all-cause mortality and a composite endpoint of cardiovascular mortality, congestive heart failure, and hospitalisation for non-fatal cardiovascular and cerebrovascular events. Secondary outcome measures are total costs, cost-effectiveness, quality of life, echocardiographic and cardiac magnetic resonance parameters, exercise tests, asymptomatic atrial fibrillation and brain natriuretic peptide levels. Additionally, the complication rate in the surgery group and rate of surgery in the watchful waiting group will be determined.ImplicationsThe Dutch AMR trial will be the first multicenter randomised trial on this topic. We anticipate that the results of this study are highly needed to elucidate the best treatment strategy and that this may prove to be an international landmark study.

Data Resource Profile: Adult cardiac surgery database of the Netherlands Association for Cardio-Thoracic Surgery

In 2007 The Netherlands Association for Cardio-Thoracic Surgery (Nederlandse Vereniging voor Thoraxchirurgie, NVT) instituted the Adult Cardiac Surgery Database. The dataset comprises demographic factors, type of intervention, in-hospital mortality and 18 risk factors for mortality after cardiac surgery, according to the European System for Cardiac Operative Risk Evaluation definitions. Currently, this procedural database contains over 60 000 interventions. Completeness of data is excellent and national coverage of all 16 Dutch cardio-thoracic surgery centres has been achieved since the start. The primary goal of the database is to control and maintain the quality of care by evaluation of outcomes. This is accomplished by regular feedback and comparison of outcomes. For a subset of the database (procedures from 10 out of 16 centres) longer-term follow-up has been established by means of data linkage to two national registries. This provides information on survival status, causes of death and readmissions. The database has recently been used for research, resulting in methodological papers aimed at optimizing comparison of outcomes. In future, clinical issues will also be addressed, for example survival after coronary artery bypass grafting and valve surgery.

Arterial stiffness and progression of structural brain changes The SMART-MR study

Objective: To examine the cross-sectional and prospective associations between arterial stiffness and structural brain changes within the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study, a prospective cohort study among patients with manifest arterial disease. Methods: Distension measurements of the common carotid arteries and a brain MRI were performed in 526 patients (mean age 59 ± 10 years). After a mean follow-up of 4.1 years (range 3.6–5.8), brain MRI was repeated in 308 patients. Brain segmentation was used to quantify total brain volume, cortical gray matter volume, ventricular volume, and white matter lesion (WML) volume (relative to intracranial volume). Infarcts were rated visually. Results: Cross-sectional multivariable regression analyses showed that 1 SD decrease in carotid distension, indicating increased arterial stiffness, was associated with smaller relative total brain and cortical gray matter volumes (B = −0.24%, 95% confidence interval [CI] −0.44 to −0.04%, and B = −0.47%, 95% CI −0.75 to −0.19%), with larger WML volume (B = 0.09%, 95% CI −0.01 to 0.19%), and with higher risk of having nonlacunar (cortical or large subcortical) brain infarcts (relative risk = 1.44, 95% CI 1.14 to 1.81). However, our prospective findings showed that carotid distension was not significantly associated with progression of brain atrophy, WML volume, or brain infarcts. Conclusion: In this population of patients with manifest arterial disease, stiffening of the carotid arteries was cross-sectionally associated with more brain atrophy, WML volume, and nonlacunar infarcts, but did not lead to changes in brain volumes or infarcts after 4 years.

Change in abdominal obesity and risk of coronary calcification

Background A prospective follow-up study was conducted to examine the relationship between 9u2005year change in abdominal obesity and risk of coronary artery calcification (CAC). Methods Data on coronary risk factors for 573 postmenopausal women were collected at baseline (1993–1997) and follow-up (2002–2004). At follow-up, the women underwent a multidetector CT to assess coronary calcium using the Agatston score. Markers of abdominal obesity were waist and hip circumference, waist-to-hip ratio (WHR) and body mass index. Results Compared to subjects whose waist circumference remained below the median at both occasions, those with a waist above the median had a 1.5-fold (95% CI 1.0 to 2.3) increased risk of CAC. Women whose waist rose over the 9u2005year period had a 2.2-fold (95% CI 1.1 to 4.2) increased risk of CAC, whereas women whose WHR became lower had a non-significant 1.5-fold increased risk of CAC (95% CI 0.7 to 3.0). In contrast, change in body mass index or hip circumference was not related to risk of CAC. Conclusion This study supports the existing evidence that persistent abdominal obesity, as well as an increase in abdominal fat, relates to an increased risk of coronary atherosclerosis.

Unrecognised myocardial infarction in subjects at high vascular risk: prevalence and determinants

Objective: To investigate the prevalence and determinants of unrecognised myocardial infarction (UMI). Design, setting, patients: In this cross-sectional study in a tertiary centre, a delayed enhancement cardiac MRI (DE-CMR), which identifies both Q-wave and non-Q wave MIs, was performed in 502 subjects with manifest extracardiac atherosclerotic disease or marked risk factors for atherosclerosis without symptomatic coronary artery disease. Main outcome measures: UMI was defined as the presence of delayed enhancement without corresponding clinical history. Results: DE-CMR was of sufficient image quality in 480 (95.6%) subjects. A UMI was present in 45 (9.4%) of all subjects; in 13.1% of men and in 3.7% of women. The risk of UMI increased from 6.0% (95% CI 2.2 to 9.8%) in those with two vascular risk factors up to 26.2% (95% CI 15.2 to 37.3%) in those with four or five risk factors. In a multivariable analysis, the risk of UMI was related to male gender (OR 2.3 (95% CI 1.0 to 5.6)), age (OR 1.04 (95% CI 1.00 to 1.07) per year), ever smoking (OR 3.1 (95% CI 1.0 to 9.1), history of stroke (OR 1.9 (95% CI 0.8 to 4.3)) and history of aneurysm of the abdominal aorta (OR 2.6 (95% CI 1.0 to 6.9)). Conclusions: In cardiac asymptomatic subjects at high vascular risk, UMI is common. The risk of UMI increases with increasing presence of risk factors.