Wall thickness of the carotid artey as an indicator of generalized atherosclerosis : the Rotterdam study

The past decades have led to a better understanding of the etiology and pathogenesis of atherosclerosis and its clinical sequelae. Several risk factors have been identified that promote atherosclerosis to develop and of which it is currently known that their presence increases the risk of cardiovascular disease. At present, cardiovascular disease is believed to be caused by an interplay of advanced atherosclerotic vessel wall changes, stenosis and thrombosis. However, the question why some people suffer from a cardiovascolar event whereas others may be SPared from SYffiptomatic cardiovascular disease remains unanswered. This is in particular important for subjects of older age, since in these subjects some extent of atherosclerosis is already present. Non-invasive techniques to accurately assess atherosclerotic vessel wall abnormalities may be used to smdy the atherosclerotic process in population-based studies in order to gain further insight in factors that initiate the atherosclerotic process, lead to progression of atherosclerosis, and cause disease to manifest itself in the absence or presence of atherosclerotic vessel wall abnormalities. High resolution B-mode ultrasonography of carotid arteries may provide a tool to study signs of early and advanced atherosclerosis, to monitor the process of development of atherosclerosis and to study factors which promote development and progression of atherosclerotic vessel wall disease and subsequent clinical cardiovascular disease in populations at large.'-" The main objectives of the studies presented in this thesis were to evaluate the feasibility of non-invasive assessment of hemodynamically important stenosis of the carotid artery and common carotid intima-media thickness, in an elderly non-hospitalized population; to study the value of increased intima-media thickness of the distal common carotid artery as an indicator of generalized atherosclerosis; to study determinants of increased common carotid intima-media thickness. In chapter 3, a general outline is given of the principles of the ultrasound technique and a detailed description of the ultrasound reading protocol as it is used in the Rotterdam Study is provided. Furthermore, the reproducibility of the ultrasonographic measurements of common carotid intima-media thickness is presented in this chapter. The associations between intima-media thickness of the distal common carotid artery and indicators of atherosclerosis in other arteries are descnoed in chapter 4. Results from studies on the association between common carotid intima-media thickness and cardiovascular risk factors are discussed in chapter 5, whereas chapter 6 deals with the prevalence and determinants of carotid atherosclerosis diagnosed as hemodynamically important stenosis. The findings presented in chapter 7 concern the association between cerebral white matter lesions and non-invasively assessed atherosclerosi

Impaired glucose tolerance and diabetes mellitus in a rural population in South India

In the present study the prevalence of impaired glucose tolerance and non-insulin dependent diabetes mellitus in a rural population in South India was assessed and its associations with body mass index and a family history of diabetes mellitus. Data were obtained from inhabitants of two villages located in the North Arcot District of Tamil Nadu. After an overnight fast, 467 randomly selected subjects, aged 40 years or over, were given 75 g glucose orally. After two hours the capillary glucose level was determined. The prevalence of impaired glucose tolerance (2 h value ≥ 7.8 mmol/l and < 11.1 mmol/l) was 6.6% (31 subjects). Non-insulin dependent diabetes mellitus (2 h value ≥ 11.1 mmol/l) was found in 23 subjects (4.9%). Of these, 53% were previously unknown. Age and sex adjusted mean body mass index was significantly higher among subjects with impaired glucose tolerance compared to subjects without glucose intolerance, with a mean difference of 1.4 kg/m2 (95% confidence interval (CI) 0.2, 2.6). A positive family history of diabetes was non-significantly higher in subjects with impaired glucose tolerance. Subjects with non-insulin-dependent diabetes mellitus had a higher mean body mass index compared to subjects with normal glucose levels with a mean difference of 1.9 kg/m2 (95% CI 0.5, 3.3). A positive family history of diabetes was more common among diabetics with a difference of 20% (95% CI 10, 30). Our findings suggest that in a considerable proportion (11.5%) of the rural South Indian population aged 40 years or over glucose intolerance is present. These results may indicate that apart from other important causes of morbidity and mortality, a substantial proportion of the rural Indian population will suffer from cardiovascular morbidity and mortality in the near future

Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study

BACKGROUND: Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. METHODS AND RESULTS: We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. CONCLUSIONS: The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events

Peripheral arterial disease in the elderly: The Rotterdam Study

To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC

Transient neurological attacks in the general population. Prevalence, risk factors, and clinical relevance

BACKGROUND AND PURPOSE: Patients with typical transient ischemic attacks (TIAs) have a higher risk of stroke but a lower risk of cardiac events than patients with nonspecific transient neurological symptoms. We assessed the prevalences of typical TIAs and nonspecific transient neurological attacks (TNAs) and their determinants in the general population because such data are virtually absent. METHODS: The Rotterdam Study is a population-based cohort study of 7983 subjects, aged 55 years and over, conducted in a district of Rotterdam, the Netherlands. At baseline examination, a history of episodes of disturbances in sensibility, strength, speech, and vision that lasted less than 24 hours and occurred within the preceding 3 years was determined by a trained physician. When such a history was present, information on time of onset, duration, and disappearance of symptoms and a detailed description of the symptoms (in ordinary language) were obtained. Subjects were classified by a neurologist as typical TIA or nonspecific TNA. RESULTS: Prevalence of TNAs was 1.9% in subjects aged 55 to 64 years, 3.5% in subjects aged 65 to 74 years, 4.3% in subjects aged 75 to 84 years, and 5.1% in subjects aged 85 years or over. Prevalence figures for typical TIA were 0.9%, 1.7%, 2.3%, and 2.2% and for nonspecific TNA 1.0%, 1.8%, 2.0%, and 2.9%, respectively. Clinical parameters such as number of attacks, onset, duration, and disappearance of symptoms were similar for typical TIA and nonspecific TNA. Increased age, male sex, diabetes mellitus, low HDL cholesterol, Q-wave myocardial infarction on electrocardiogram, and carotid atherosclerosis were related to typical TIA, whereas increased age, hypertension, low HDL cholesterol, smoking, and angina pectoris were associated with nonspecific TNA. CONCLUSIONS: About half of the subjects with a TNA had symptoms that were not entirely typical for a TIA. Differences in associations with risk factors between typical TIA and nonspecific TNA point toward different underlying mechanisms of symptoms and may lead to different ancillary investigations and possibly treatment

J-shaped relation between blood pressure and stroke in treated hypertensives

The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly. The study was performed within the framework of the Rotterdam Study, a prospective population-based cohort study. The risk of first-ever stroke was associated with hypertension (relative risk, 1.6; 95% CI, 1.2 t

Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam Study

OBJECTIVE: To estimate the incidence, survival, and lifetime risk of stroke in the elderly population. METHODS: The authors conducted a study in 7,721 participants from the population based Rotterdam Study who were free from stroke at baseline (1990-1993) and were followed up for stroke until 1 January 1999. Age and sex specific incidence, case fatality rates, and lifetime risks of stroke were calculated. RESULTS: Mean follow up was 6.0 years and 432 strokes occurred. The incidence rate of stroke per 1,000 person years increased with age and ranged from 1.7 (95% CI 0.4 to 6.6) in men aged 55 to 59 years to 69.8 (95% CI 22.5 to 216.6) in men aged 95 years or over. Corresponding figures for women were 1.2 (95% CI 0.3 to 4.7) and 33.1 (95% CI 17.8 to 61.6). Men and women had similar absolute lifetime risks of stroke (21% for those aged 55 years). The survival after stroke did not differ according to sex. CONCLUSIONS: Stroke incidence increases with age, also in the very old. Although the incidence rate is higher in men than in women over the entire age range, the lifetime risks were similar for both sexes

Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study

Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [beta]=-0.023, 95% CI -0.033 to -0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent