BACKGROUND—Cerebral microbleeds are highly prevalent in people with clinically manifest cerebrovascular disease and have been shown to increase the risk of stroke recurrence. Microbleeds are also ...frequently found in healthy elderly, a population in which the clinical implication of microbleeds is unknown.
METHODS AND RESULTS—In the population-based Rotterdam Study, the presence, number, and location of microbleeds were assessed at baseline on brain MRI of 4759 participants aged ≥45 years. Participants were followed for incident stroke throughout the study period (2005–2013). We used Cox proportional hazards to investigate if people with microbleeds were at increased risk of stroke in comparison with those without microbleeds, adjusting for demographic, genetic, and cardiovascular risk, and cerebrovascular imaging markers. Microbleed prevalence was 18.7% (median count 1 1–111). During mean follow-up of 4.9 years (standard deviation, 1.6) 93 strokes occurred (72 ischemic, 11 hemorrhagic, and 10 unspecified). Microbleed presence was associated with an increased risk of all strokes (hazard ratio, 1.93; 95% confidence interval, 1.25–2.99). The risk increased with greater microbleed count. In comparison with those without microbleeds, participants with microbleeds in locations suggestive of cerebral amyloid angiopathy (lobar with or without cerebellar microbleeds) were at increased risk of intracerebral hemorrhage (hazard ratio, 5.27; 95% confidence interval, 1.38–20.23). Microbleeds at other locations were associated with an increased risk of both ischemic stroke and intracerebral hemorrhage.
CONCLUSIONS—Microbleeds on MRI are associated with an increased risk of stroke in the general population. Our results strengthen the notion that microbleeds mark progression of cerebrovascular pathology and represent a precursor of stroke.
Cardiovascular factors and low education are important risk factors of dementia. We provide contemporary estimates of the proportion of dementia cases that could be prevented if modifiable risk ...factors were eliminated, i.e., population attributable risk (PAR). Furthermore, we studied whether the PAR has changed across the last two decades.
We included 7,003 participants of the original cohort (starting in 1990) and 2,953 participants of the extended cohort (starting in 2000) of the Rotterdam Study. Both cohorts were followed for dementia until ten years after baseline. We calculated the PAR of overweight, hypertension, diabetes mellitus, cholesterol, smoking, and education. Additionally, we assessed the PAR of stroke, coronary heart disease, heart failure, and atrial fibrillation. We calculated the PAR for each risk factor separately and the combined PAR taking into account the interaction of risk factors.
During 57,996 person-years, 624 participants of the original cohort developed dementia, and during 26,177 person-years, 145 participants of the extended cohort developed dementia. The combined PAR in the original cohort was 0.23 (95 % CI, 0.05-0.62). The PAR in the extended cohort was slightly higher at 0.30 (95 % CI, 0.06-0.76). The combined PAR including cardiovascular diseases was 0.25 (95 % CI, 0.07-0.62) in the original cohort and 0.33 (95 % CI, 0.07-0.77) in the extended cohort.
A substantial part of dementia cases could be prevented if modifiable risk factors would be eliminated. Although prevention and treatment options of cardiovascular risk factors and diseases have improved, the preventive potential for dementia has not declined over the last two decades.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework.Design Prospective population based cohort study.Setting ...People living in the community in Rotterdam, the Netherlands.Participants 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline.Main outcome measures First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death.Results During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were −7 for any cardiovascular disease, −102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and −1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke.Conclusions At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
IMPORTANCE Intracranial atherosclerosis represents a relatively unexplored, but potentially important, cause of stroke in a white population. OBJECTIVE To investigate the relationship between ...intracranial carotid artery calcification (ICAC) as a marker of intracranial atherosclerosis and the risk of stroke in whites. DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study in the general community with 6 years of follow-up was conducted (the Rotterdam Study). Between 2003 and 2006, a random sample of 2323 stroke-free persons (mean age, 69.5 years) underwent computed tomography scanning to quantify ICAC volume. All participants were continuously monitored for the occurrence of stroke until January 1, 2012. EXPOSURE Atherosclerotic calcification in the intracranial internal carotid arteries. MAIN OUTCOME AND MEASURE Incident stroke. RESULTS During 14 055 person-years of follow-up, 91 participants had a stroke, of which 74 were ischemic. Larger ICAC volume was related to a higher risk of stroke, independent of cardiovascular risk factors, ultrasound carotid plaque score, and calcification in other vessels (fully adjusted hazard ratio per an increase of 1 SD in ICAC volume, 1.43 95% CI, 1.04-1.96). Intracranial carotid artery calcification contributed to 75% of all strokes; for aortic arch and extracranial carotid artery calcification this incidence was only 45% and 25%, respectively. CONCLUSIONS AND RELEVANCE Our findings establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the proportion of all strokes may be greater than that of large-artery atherosclerosis in more proximally located vessel beds.
BACKGROUND AND PURPOSE—Improved short-term survival after stroke has necessitated quantifying risk and risk factors of long-term sequelae after stroke (ie, recurrent stroke and dementia). This risk ...may be influenced by exposure to cardiovascular risk factors before the initial stroke. Within the population-based Rotterdam Study, we determined the long-term risk of recurrent stroke and dementia, and the proportion of recurrent strokes and poststroke dementia cases that are attributable to prestroke cardiovascular risk factors (ie, the population attributable risk).
METHODS—We followed up 1237 patients with first-ever stroke and 4928 stroke-free participants, matched on age, sex, examination round, and stroke date (index date), for the occurrence of stroke or dementia. We calculated incidence rates in both groups and estimated the individual and combined population attributable risk of prestroke cardiovascular risk factors for both outcomes.
RESULTS—Beyond 1 year after stroke, patients retained a 3-fold increased risk of recurrent stroke and an almost 2-fold increased risk of dementia compared with people without stroke. In total, 39% (95% confidence interval, 18%–66%) of recurrent strokes and 10% (95% confidence interval, 0%–91%) of poststroke dementia cases were attributable to prestroke cardiovascular risk factors. These percentages were similar for first-ever stroke and dementia in the matched stroke-free population.
CONCLUSIONS—Long-term risks of recurrent stroke and poststroke dementia remain high and are substantially influenced by prestroke risk factors, emphasizing the need for optimizing primary prevention.
BACKGROUND AND PURPOSE—Because atherosclerosis is a systemic disease, presence and composition on 1 location may relate to ischemic events in distant locations. We examined whether carotid ...atherosclerotic wall thickness, stenosis, and plaque composition are related to history of ischemic stroke and coronary heart disease (CHD).
METHODS—From the population-based Rotterdam Study, 1731 asymptomatic participants (mean age, 72.4±9.1 years; 55% males) underwent magnetic resonance imaging of both carotid arteries. We assessed carotid wall thickness, stenosis and plaque composition, that is presence of intraplaque hemorrhage, lipid, and calcification. History of ischemic stroke and CHD was assessed until date of magnetic resonance imaging. The study was approved by the institutional review board, and all participants gave informed consent. Logistic regression analyses adjusted for age and traditional cardiovascular risk factors were used to study sex-specific associations between plaque characteristics and clinical events.
RESULTS—We found that both carotid stenosis and intraplaque hemorrhage were associated with ischemic stroke in men but not in women (menodds ratio OR for stenosis per 10% increase1.17 95% CI, 1.06–1.30 and for intraplaque hemorrhage 2.39 95% CI, 1.32–4.35). In both men and women, carotid stenosis was associated with CHD (menOR per 10% increase 1.12 95% CI, 1.04–1.21 and womenOR, 1.17 95% CI, 1.03–1.34) and carotid wall thickness was associated with CHD (menOR, 1.20 95% CI, 1.03–1.39 and womenOR, 1.21 95% CI, 0.88–1.65). None of the plaque components was associated with CHD.
CONCLUSIONS—Whereas carotid plaque thickness and stenosis are associated with the history of ischemic stroke and CHD, carotid intraplaque hemorrhage is associated with ischemic stroke, but not with CHD, providing novel insights into the pathogenesis of cardiovascular events.
Hypertension is a major modifiable risk factor for stroke. Associations of blood pressure with incident stroke are mostly based on single or average blood pressure levels. However, this approach does ...not take into account long-term trajectories of blood pressure, which can vary considerably in the elderly. Within the population-based Rotterdam Study, we examined trajectories of systolic blood pressure in 6745 participants (60.0% women) over an age-range from 55 to 106 years and jointly modeled their risk of stroke and competing causes of death using joint latent class mixed modeling. Four trajectories were identified. Class 1 was characterized by blood pressure increasing gradually from on average 120 to 160 mm Hg over 5 decades (n=4938). Compared with this class, class 2, characterized by a similar midlife blood pressure, but a steep increase (n=822, increasing from 120 to 200 mm Hg), and class 4, characterized by a high midlife blood pressure (n=115; average 160 mm Hg) and had a higher risk of stroke and death. Class 3, characterized by a moderate midlife blood pressure (n=870; average 140 mm Hg), had a similar risk of death as class 1, but the highest risk of stroke. Assessing trajectories of blood pressure provides a more nuanced understanding of the associations between blood pressure, stroke, and mortality. In particular, high blood pressure and rapidly increasing blood pressure patterns are associated with a high risk of stroke and death, whereas moderately high blood pressure is only related to an increased risk of stroke. Future studies should explore the potential pathogenic significance of these patterns.
Accumulating vascular pathology in cerebral arteries leads to impaired cerebral vasomotor reactivity. In turn, impaired cerebral vasomotor reactivity is a risk factor for stroke in clinical ...populations. It remains unclear whether impaired cerebral vasomotor reactivity also reflects more systemic vascular damage. We investigated whether cerebral vasomotor reactivity is associated with the risk of mortality, focusing particularly on cardiovascular mortality independent from stroke.
Between 1997 and 1999, 1695 participants from the Rotterdam Study underwent cerebral vasomotor reactivity measurements using transcranial Doppler. Follow-up was complete until January 1, 2011. We assessed the associations between cerebral vasomotor reactivity and mortality using Cox proportional hazards models, adjusting for age, sex, and blood pressure changes and subsequently for cardiovascular risk factors. We additionally censored for incident stroke.
During 17 004 person-years, 557 participants died, of whom 181 due to a cardiovascular cause. In the fully adjusted model, the hazard ratio per SD decrease in vasomotor reactivity was 1.10 (95% confidence interval CI, 1.01-1.19) for all-cause mortality, 1.09 (95% CI, 0.94-1.26) for cardiovascular mortality, and 1.10 (95% CI, 0.99-1.21) for noncardiovascular mortality. These associations remained unchanged after censoring for incident stroke.
We found that lower cerebral vasomotor reactivity is associated with an increased risk of death. Incident stroke does not affect this association, suggesting that a lower cerebral vasomotor reactivity reflects a generally impaired vascular system.
Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are leading causes of death. Increasing evidence suggests an association between both diseases, either caused by an increased ...atherosclerosis risk in patients with COPD or as a consequence of shared risk factors between stroke and COPD.
To examine the associations between COPD and subtypes of stroke in the general population and to explore the role of cardiovascular risk factors and exacerbations on these associations.
Within the prospective population-based Rotterdam Study, we followed 13,115 participants without history of stroke for occurrence of stroke. Follow up started in 1990 to 2008 and ended in 2012. COPD was related to stroke using a time-dependent Cox proportional hazard model.
COPD was diagnosed in 1,566 participants. During 126,347 person-years, 1,250 participants suffered a stroke, of which 701 were ischemic and 107 hemorrhagic. Adjusted for age, age squared, and sex, COPD was significantly associated with all stroke (hazard ratio HR, 1.20; 95% confidence interval, 1.00-1.43), ischemic stroke (HR, 1.27; 1.02-1.59), and hemorrhagic stroke (HR, 1.70; 1.01-2.84). Adjusting for cardiovascular risk factors gave similar effect sizes. In contrast, additional adjusting for smoking attenuated the effect sizes: HR, 1.09 (0.91-1.31) for all stroke; HR, 1.13 (0.91-1.42) for ischemic stroke; and HR 1.53 (0.91-2.59) for hemorrhagic stroke. After an acute severe exacerbation, subjects with COPD had a 6.66-fold (2.42-18.20) increased risk of stroke.
Our cohort study demonstrated a higher risk of both ischemic and hemorrhagic stroke in subjects with COPD and revealed the importance of smoking as a shared risk factor.
OBJECTIVE:To investigate the association between cardiac function and the risk of stroke and dementia in elderly free of clinical cardiac disease. Additionally, we investigated the relation between ...cardiac function and MRI markers of subclinical cerebrovascular disease.
METHODS:This study was conducted within the population-based Rotterdam Study. A total of 3,291 participants (60.8% female, age-range 58–98 years) free of coronary heart disease, heart failure, atrial fibrillation, stroke, and dementia underwent echocardiography in 2002–2005 to measure cardiac function. Follow-up finished in 2012. In 2005–2006, a random subset of 577 stroke-free people without dementia underwent brain MRI on which infarcts and white matter lesion volume were assessed.
RESULTS:During 21,785 person-years of follow-up, 164 people had a stroke and during 19,462 person-years of follow-up, 208 people developed dementia. Measures of better diastolic function, such as higher E/A ratio, were associated with a lower risk of stroke (hazard ratio HR 0.82; 95% confidence interval CI 0.69; 0.98) and dementia (HR 0.82; 95% CI 0.70; 0.96). Better systolic function, measured as higher fractional shortening, was only associated with a lower risk of stroke (HR 0.84; 95% CI 0.72; 0.98). Better diastolic function was related to a lower prevalence of silent infarcts on MRI, especially lacunar infarcts.
CONCLUSIONS:In elderly free of clinical cardiac disease, worse diastolic function is associated with clinical stroke, dementia, and silent infarcts on MRI, whereas worse systolic function is related only to clinical stroke. These findings can form the basis for future research on the utility of cardiac function as potential intervention target for prevention of neurologic diseases.
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