Carmine Marini

Contribution of Atrial Fibrillation to Incidence and Outcome of Ischemic Stroke Results From a Population-Based Study

Background and Purpose— Atrial fibrillation (AF) is a major risk factor for ischemic stroke and its prevalence increases steeply with age. Population-based data on its influence on stroke outcome are scarce. Methods— We evaluated the prevalence of AF and its influence on prognosis in patients with a first-ever ischemic stroke from a population-based registry. Results— The presence of AF at stroke onset and during the acute phase was confirmed by a standard electrocardiogram in 869 (24.6%) of 3530 patients with ischemic stroke. With respect to patients without the arrhythmia, those with AF were more frequently women, aged 80 years and older, with coronary heart disease and peripheral arterial disease. The presence of AF was associated with high 30-day (32.5%; 95% CI, 29.3 to 35.6) and 1-year case-fatality rates (49.5%; 95% CI, 46.2 to 52.8), with a higher stroke recurrence rate within the first year of follow-up (6.6% versus 4.4%; P=0.046) and with the worst survival after an average follow-up of 45.2 months (P<0.0001). At the multivariate Cox regression analysis, AF was an independent predictor of 30-day and 1-year mortality. Approximately 17% of all deaths were attributable to the presence of AF. Conclusions— We found a high prevalence of AF in patients with a first-ever ischemic stroke, especially among elderly women. The overall contribution of AF to stroke mortality was relevant, suggesting that together with new strategies to prevent the development of the arrhythmia more appropriate treatments are needed, mostly in elderly women.

History of migraine and risk of cerebral ischaemia in young adults

BACKGROUND A history of migraine has been proposed as a risk factor for cerebral ischaemia in women under 45. METHODS To investigate the association between history of migraine and cerebral ischaemia, we performed a case-control study of 308 patients aged 15-44, with either transient ischaemic attack (TIA) or stroke, and of 591 age- and sex-matched controls prospectively recruited in seven university hospitals. Crude and adjusted odds ratios were calculated using logistic regression analysis. FINDINGS A history of migraine was more frequent in patients than in controls (14.9% vs 9.1%; adjusted odds ratio 1.9, 95% confidence interval 1.1-3.1). In the prospectively designed subgroup analyses, a history of migraine reached the highest odds ratio (3.7, 95% CI 1.5-9) and was the only significant risk factor in women below age 35 (p=0.003); atherogenic risk factors were more relevant in men and in patients older than 35; previous migraine attacks with aura were more frequent in stroke patients (odds ratio 8.6, 95% CI 1-75). INTERPRETATION Our findings indicated that the rare association between migraine and cerebral ischaemia is limited to women below age 35, and suggest a need for careful clinical evaluation of comorbidity in the presence of migraine with aura.

Incidence and 10-Year Survival of Intracerebral Hemorrhage in a Population-Based Registry

Background and Purpose— The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage. Methods— We analyzed data referring to our prospective population-based registry, including patients with a first-ever stroke followed up to 10 years. Results— In a 5-year period, we included 549 patients (247 men and 302 women; mean age±SD, 73.6±12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100 000 (95% CI, 33.8 to 40.0), 32.9 per 100 000 when standardized to the 2006 European population, and 15.9 per 100 000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7- and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan–Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1). Conclusions— Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.

Burden of first-ever ischemic stroke in the oldest old: Evidence from a population-based study

Objective: To evaluate the contribution of subjects 80 years old or older to the burden of ischemic stroke as compared with subjects younger than 80 years. Methods: All first-ever ischemic strokes occurring in a 5-year period (1994 to 1998) in the population-based L’Aquila registry were traced. Incidence, total health care utilization, disability, and mortality were assessed in patients 80 years old or older, and differences with those younger than 80 years were assessed by univariate and survival analyses. Results: One thousand three hundred sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80 years old or older, accounting on average for one-third of health care utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to 22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability, 20.7% had severe disability, and 51.6% had died. With respect to patients under 80 years of age, older patients showed a higher proportion of women (61.3 vs 47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs 23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%). Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in patients 80 years old or older than in those younger than 80, mostly in the presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day mortality and 1.31 for 1-year mortality). Conclusion: The burden of ischemic stroke is high in subjects 80 years old or older, contributing about one-third of health care utilization and 59.8% of deaths within 30 days.

A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants. The National Research Council Study Group.

Background and Purpose The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. Methods Three hundred thirty-three patients aged 15–44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. Results Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. Conclusions Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors.

Stroke in young adults in the community-based L'Aquila registry: incidence and prognosis.

Background and Purpose— Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population. Methods— All first-ever strokes occurring in the L’Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale. Results— Of 4353 patients who had a first-ever stroke, 89 patients <45 years of age (55 men and 34 women) (2%) were identified in a 5-year period. Mean age±SD was 36.1±8.1 years. Twenty patients (22.5%) had a subarachnoid hemorrhage, 18 (20.2%) an intracerebral hemorrhage, and 51 (57.3%) a cerebral infarction. The corresponding proportions in patients >45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100 000 (95% CI, 8.14 to 12.57) and 10.23/100 000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%). Conclusions— Stroke patients <45 years of age showed a disproportionate cumulative high prevalence (42.7%) of subarachnoid and intracerebral hemorrhage with respect to older patients (15.7%), mainly (52.6%) due to aneurysms and arteriovenous malformations. Therefore, screening procedures and preventive strategies in the young should also be addressed to subjects at risk of subarachnoid and intracerebral hemorrhage.

Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive Impairment The Cocoa, Cognition, and Aging (CoCoA) Study

Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols) of cocoa flavanols per day. Cognitive function was assessed by Mini Mental State Examination, Trail Making Test A and B, and verbal fluency test. At the end of the follow-up period, Mini Mental State Examination was similar in the 3 treatment groups (P=0.13). The time required to complete Trail Making Test A and Trail Making Test B was significantly (P<0.05) lower in subjects assigned to high flavanols (38.10±10.94 and 104.10±28.73 seconds, respectively) and intermediate flavanols (40.20±11.35 and 115.97±28.35 seconds, respectively) in comparison with those assigned to low flavanols (52.60±17.97 and 139.23±43.02 seconds, respectively). Similarly, verbal fluency test score was significantly (P<0.05) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols (27.50±6.75 versus 22.30±8.09 words per 60 seconds). Insulin resistance, blood pressure, and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups. Changes of insulin resistance explained ≈40% of composite z score variability through the study period (partial r2=0.4013; P<0.0001). To the best of our knowledge, this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment. This effect appears mediated in part by an improvement in insulin sensitivity.

A population-based study of the incidence and prognosis of lacunar stroke

Objective: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. Methods: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. Results: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95% CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3% (95% CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0% (95% CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95% CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95% CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. Conclusion: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.

Long-Term Prognosis of Cerebral Ischemia in Young Adults

Background and Purpose —Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. Methods —Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. Results —An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P P =0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6.04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. Conclusions —Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.

Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study—a randomized controlled trial

Background: Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities. Objective: The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects. Design: This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT). Results: The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (−8.6 ± 0.4 and −16.5 ± 0.8 s, respectively) and IF (−6.7 ± 0.5 and −14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (−0.8 ± 1.6 and −1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r2 = 0.1703, P < 0.0001). Conclusions: This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. This trial was registered at www.controlled-trials.com as ISRCTN68970511.