Aortic stiffness and the balance between cardiac oxygen supply and demand: the Rotterdam Study.

OBJECTIVES: Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality. We investigated whether aortic stiffness, estimated as aortic pulse wave velocity, is associated with decreased perfusion pressure estimated as the cardiac oxygen supply potential. METHODS: Aortic stiffness and aortic pressure waves, reconstructed from finger blood pressure waves, were obtained in 2490 older adults within the framework of the Rotterdam Study, a large population-based study. Cardiac oxygen supply and demand were estimated using pulse wave analysis techniques, and related to aortic stiffness by linear regression analyses after adjustment for age, sex, mean arterial pressure and heart rate. RESULTS: Cardiac oxygen demand, estimated as the Systolic Pressure Time Index and the Rate Pressure Product, increased with increasing aortic stiffness [0.27 mmHg s (95% confidence interval: 0.21; 0.34)] and [42.2 mmHg/min (95% confidence interval: 34.1; 50.3)], respectively. Cardiac oxygen supply potential estimated as the Diastolic Pressure Time Index decreased [-0.70 mmHg s (95% confidence interval: -0.86; -0.54)] with aortic stiffening. Accordingly, the supply/demand ratio Diastolic Pressure Time Index/Systolic Pressure Time Index -1.11 (95% confidence interval: -0.14; -0.009) decreased with increasing aortic stiffness. CONCLUSION: Aortic stiffness is associated with estimates of increased cardiac oxygen demand and a decreased cardiac oxygen supply potential. These results may offer additional explanation for the relation between aortic stiffness and cardiovascular morbidity and mortality.

Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults: the Rotterdam Study.

OBJECTIVE: Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was to investigate the association between aortic stiffness and coronary atherosclerosis. METHODS: The study was performed in 1757 subjects of the Rotterdam Study, a population-based study of elderly individuals. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWV). Coronary atherosclerosis was assessed by measuring coronary calcification using electron beam tomography and expressed as a total calcium score. The total calcium score was log-transformed because of its skewed distribution. The association between PWV and coronary calcification was first evaluated after adjustment for age, sex, mean arterial blood pressure and heart rate. RESULTS: Linear regression analyses showed that increased PWV was associated with a higher log total coronary calcium score [beta-regression coefficient 0.11, 95% confidence interval (CI) 0.07-0.15]. Compared with the lowest quartile of PWV, multivariate odds ratios and corresponding 95% CI for advanced coronary calcification in the second, third and fourth highest quartiles were 1.17 (0.79-1.74), 1.58 (1.07-2.34) and 2.12 (1.40-3.20), respectively. CONCLUSIONS: In this large population-based study performed in elderly subjects aortic stiffness was strongly and independently associated with coronary atherosclerosis.

Impaired fasting glucose is associated with increased arterial stiffness in elderly people without diabetes mellitus: the Rotterdam Study.

OBJECTIVES: To study the association between impaired fasting glucose (IFG) and arterial stiffness in older adults. DESIGN: Cross-sectional population-based study. SETTING: The Rotterdam Study, a Dutch population-based cohort study. PARTICIPANTS: Two thousand nine hundred eighty-seven subjects aged 60 and older. MEASUREMENTS: Arterial stiffness assessed by measuring common carotid arterial distensibility and glucose status classified into three categories: normal fasting glucose (NFG) (fasting glucose <6.1 mmol/L), IFG (fasting glucose 6.1-6.9 mmol/L), and diabetes mellitus (DM). RESULTS: In the total cohort, common carotid distensibility decreased with increasing impairment of glucose metabolism. Subjects younger than 75 with IFG were comparable with subjects with NFG with respect to arterial stiffness. Subjects aged 75 and older with IFG had stiffer arteries than subjects with NFG, reaching the same arterial stiffness as subjects with DM. For subjects younger than 75, mean difference in distensibility coefficient between subjects with NFG and with IFG was 0.1 (95% confidence interval (CI)=-0.04-0.05, P=.88) and between subjects with NFG and with DM was 1.2 (95% CI=0.7-1.7, P<.001). For subjects aged 75 and older, the mean difference between these groups was 0.7 (95% CI=0.2-1.2, P=.007) and 0.8 (0.3-1.4; P=.002), respectively. In the total cohort, fasting glucose was strongly associated with carotid distensibility (beta-coefficient=-0.29, P<.001). CONCLUSION: IFG is related to arterial stiffness in elderly subjects. An advanced stage of arterial stiffness, comparable with that of subjects with DM, is only reached at the age of 75.

Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study.

BACKGROUND: Arterial stiffness has been associated with the risk of cardiovascular disease in selected groups of patients. We evaluated whether arterial stiffness is a predictor of coronary heart disease and stroke in a population-based study among apparently healthy subjects. METHODS AND RESULTS: The present study included 2835 subjects participating in the third examination phase of the Rotterdam Study. Arterial stiffness was measured as aortic pulse wave velocity and carotid distensibility. Cox proportional hazards regression analysis was performed to compute hazard ratios. During follow-up, 101 subjects developed coronary heart disease (mean follow-up period, 4.1 years), and 63 subjects developed a stroke (mean follow-up period, 3.2 years). The risk of cardiovascular disease increased with increasing aortic pulse wave velocity index. Hazard ratios and corresponding 95% CIs of coronary heart disease for subjects in the second and third tertiles of the aortic pulse wave velocity index compared with subjects in the reference category were 1.72 (0.91 to 3.24) and 2.45 (1.29 to 4.66), respectively, after adjustment for age, gender, mean arterial pressure, and heart rate. Corresponding estimates for stroke were 1.22 (0.55 to 2.70) and 2.28 (1.05 to 4.96). Estimates decreased only slightly after adjustment for cardiovascular risk factors, carotid intima-media thickness, the ankle-arm index, and pulse pressure. The aortic pulse wave velocity index provided additional predictive value above cardiovascular risk factors, measures of atherosclerosis, and pulse pressure. Carotid distensibility as measured in this study was not independently associated with cardiovascular disease. CONCLUSIONS: Aortic pulse wave velocity is an independent predictor of coronary heart disease and stroke in apparently healthy subjects.

Blood pressure components and cardiovascular events in older adults: the Rotterdam study.

OBJECTIVES: To compare the strength of the relative risks of systolic (SBP) diastolic blood pressure (DBP) and pulse pressure (PP) as predictors of myocardial infarction and stroke in older adults. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: A total of 4,234 subjects aged 55 and older with no previous myocardial infarction (MI) or stroke at baseline. MEASUREMENTS: Blood pressure levels at baseline, first MI and stroke, all-cause mortality during follow-up. RESULTS: During follow-up, 205 subjects had an MI (average follow-up period 7 years), 137 subjects had a stroke (average follow-up period 6.1 years), and 748 subjects died. A 1-standard deviation difference in SBP, DBP, and PP was associated with relative risks of MI of 1.24 (95% confidence interval (CI)=1.06-1.46), 1.07 (0.92-1.25), and 1.25 (1.07-1.48), respectively. Corresponding relative risks for stroke were 1.59 (1.37-1.86), 1.27 (1.10-1.48), and 1.48 (1.27-1.72). For all-cause mortality the corresponding relative risks and 95% CI were 1.21 (1.11-1.31), 1.06 (0.99-1.14), and 1.20 (1.10-1.31). CONCLUSION: The results of this study suggest that, in a population of apparently healthy older adults, PP is not a better predictor of cardiovascular events and all-cause mortality than SBP.

Angiotensin-converting enzyme gene polymorphism and common carotid stiffness. The Rotterdam study.

The insertion/deletion (I/D) polymorphism of the ACE gene may be involved in structural arterial changes. Aim of the present study was to assess the relationship between the ACE I/D gene and vessel wall stiffness among older adults. The study was conducted within the Rotterdam study, a population-based cohort study including subjects aged 55 years and older. The II, ID and DD genotypes of the ACE gene were determined in all subjects. The distensibility coefficient (10(-3)/kPa) of the carotid artery and the carotid-femoral pulse wave velocity were measured during the third phase of the Rotterdam study (1997-1999) and were used as measure of arterial stiffness. Data on both carotid stiffness and the ACE genotype were available for 3001 participants. After adjustment for age and gender, subjects with the ID and DD genotype had higher carotid stiffness compared to subjects with II genotype (distensibility coefficient (10(-3)/kPa) 10.24 (95% CI, 10.06-10.43), 10.27 (95% CI, 10.02-10.52), 10.65 (95% CI, 10.37-10.93), respectively (ID versus II genotype, P = 0.017), (DD versus II genotype, P = 0.037)). In stratified analyses, the association was strongest in subjects younger than 70 years. No difference was seen for pulse wave velocity among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with higher common carotid stiffness.

Late-life depression is associated with arterial stiffness: a population-based study.

OBJECTIVES: To determine whether arterial stiffness is associated with depression in the elderly. DESIGN: Population-based cross-sectional study. SETTING: In Ommoord, a suburb of Rotterdam, the Netherlands. PARTICIPANTS: Three thousand seven hundred four subjects of the Rotterdam Study aged 60 and older. MEASUREMENTS: Arterial stiffness was assessed using the distensibility of the carotid artery and the carotid-femoral pulse wave velocity. All participants were screened for depressive symptoms with the Center for Epidemiologic Studies-Depression scale. Those with depressive symptoms had a psychiatric evaluation to establish a diagnosis of depressive disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: Participants with increased arterial stiffness were more likely to have depressive symptoms. Odds ratios (ORs) for depressive symptoms were 1.24 (95% confidence interval (CI) = 1.01-1.52) per standard deviation decrease in carotid distensibility and 1.17 (95% CI = 1.00-1.38) per standard deviation increase in aortic pulse wave velocity. The association was stronger for depressive disorders meeting DSM-IV criteria (OR = 1.44, 95% CI = 1.03-2.03; OR = 1.48, 95% CI = 1.16-1.90, respectively). Control for atherosclerosis, as measured by the ankle-to-brachial index or presence of plaques in the carotid artery, did not change the associations. CONCLUSION: This study shows an association between arterial stiffness and depression in the elderly. The findings are compatible with the vascular depression hypothesis. These data suggest that arterial stiffness may partly cause the proposed relationship between vascular factors and depression.

Intima-media thickness of the common carotid arteries is related to coronary atherosclerosis and left ventricular hypertrophy in older adults.

Increased intima-media thickness (IMT) of the common carotid arteries is related to generalized atherosclerosis and increased risk of future myocardial infarction and cerebrovascular disease. An association between IMT and the presence of coronary artery disease (CAD) has been documented, but controversial data have been found about the relation between increased IMT and the extent of CAD. An association between carotid atherosclerosis and cardiac remodeling has also been reported. It is still unclear whether increased IMT of the common carotid arteries might be associated with prevalent cardiovascular disease in older adults. This study included 70 patients, 37 with CAD and 33 matched for age and gender without CAD. All patients underwent a baseline clinical examination, B-mode ultrasound of the carotid arteries, and echocardiography. The authors evaluated the possible association between increased IMT with the presence and extent of CAD and the presence of left ventricular hypertrophy (LVH). The patients with CAD had significantly increased IMT compared to patients without CAD. IMT was found to increase with the number of coronary vessels affected, after adjustment for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, and smoking habits. The test for trend was highly significant (p<0.001). Patients with LVH had significantly increased IMT as compared with patients without LVH. IMT of the common carotid arteries was increased in the presence of CAD and increased with the number of coronary vessels diseased. Second, the authors found that IMT of the common carotid arteries was significantly increased in patients with LVH. Increased IMT, as an indicator of subclinical cardiovascular disease, may help to identify patients who would benefit from aggressive therapeutic measures.