Traffic-borne pollution as a risk factor for acute vascular events: a population study in Milan

Abstract Background Traffic-borne noise and air pollution have both been associated with cardiovascular and cerebrovascular diseases, albeit with inconsistent findings and issues of collinearity/mutual confounding. The present study aims at evaluating the role of long-term exposure to traffic-borne pollution as a risk factor for acute vascular events in a highly urbanized setting. Methods This is a population-based retrospective dynamic cohort study including all residents aged >35 years in the municipality of Milan over the years 2011-2018 (N = 1087110). A noise predictive model and a NO2 land-use regression model were used to assign mean values of traffic noise at the day-evening-night level (Lden, dB) and NO2 concentration (µg/m3) to the residential address of each subject. Cox proportional hazards models were performed to assess the incidence of acute vascular events, with adjustment for potential confounders (age, sex, nationality, a socio-economic deprivation index) and sub-analyses for different outcomes (acute myocardial infarction, ischemic stroke, hemorrhagic stroke). Results A total of 27282 subjects (2.5%) had an acute vascular event. Models using NO2 yielded inconsistent results. When using Lden as a proxy of traffic intensity, there was a positive trend in risk with increasing levels of exposure, with an optimal cut-off for dichotomization set at 70 dB (HR 1.025, 95% C.I. 1.000-1.050). The association was observed specifically for ischemic stroke (HR 1.043, 95% C.I. 1.003-1.085) and hemorrhagic stroke (HR 1.036, 95% C.I. 0.969-1.107). When stratifying by age group and sex, a remarkable effect was found for hemorrhagic stroke in men aged <60 (HR 1.439, 95% C.I. 1.156-1.792). Conclusions Living close to high-traffic roads was found to exert a small but tangible effect on the risk of stroke. The varying effects observed for specific outcomes and in different age and sex groups are likely due to different pathogenetic mechanisms at play, which warrant further investigation. Key messages Residential proximity to roads with high traffic intensity (mean traffic noise level over 70 dB) is a risk factor for stroke, especially for hemorrhagic stroke in middle-aged men. Further interventions aimed at reducing traffic intensity in highly urbanized cities may be justified in order to reduce morbidity and mortality from stroke.

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Abstract 2646: Aortic Arch Plaques and Risk of Vascular Events in Subjects Without Prior Stroke

Circulation ◽

10.1161/circ.118.suppl_18.s_760 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cesare Russo ◽

Zhezhen Jin ◽

Ralph L Sacco ◽

Shunichi Homma ◽

Tatjana Rundek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Aortic Arch ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Vascular Events ◽

Increased Risk ◽

Prior Stroke

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.

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Abstract 140: Association Between Epilepsy and the Risk of Ischemic Stroke or Myocardial Infarction

Stroke ◽

10.1161/str.48.suppl_1.140 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Matthew A Mercuri ◽

Alexander E Merkler ◽

Neal S Parikh ◽

Michael E Reznik ◽

Hooman Kamel

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Ischemic Stroke ◽

Elderly Patients ◽

Proportional Hazards ◽

Predictor Variable ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Increased Risk ◽

Acute Mi

Background: Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events. Hypothesis: Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI). Methods: We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated ICD-9-CM code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014. Results: Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04). Conclusions: We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.

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Fine particulate matter exposure and incidence of stroke

Neurology ◽

10.1212/wnl.0000000000003903 ◽

2017 ◽

Vol 88 (18) ◽

pp. 1709-1717 ◽

Cited By ~ 29

Author(s):

Hong Qiu ◽

Shengzhi Sun ◽

Hilda Tsang ◽

Chit-Ming Wong ◽

Ruby Siu-yin Lee ◽

...

Keyword(s):

Ischemic Stroke ◽

Particulate Matter ◽

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Fine Particulate Matter ◽

Cox Proportional Hazards ◽

Fine Particulate ◽

Chinese Cohort ◽

First Occurrence

Objective:We aimed to assess the association of long-term residential exposure to fine particulate matter (PM) with aerodynamic diameter less than 2.5 μm (PM2.5) with the incidence of stroke and its major subtypes.Methods:We ascertained the first occurrence of emergency hospital admission for stroke in a Hong Kong Chinese cohort of 66,820 older people (65+ years) who enrolled during 1998–2001 (baseline) and were followed up to December 31, 2010. High-resolution (1 × 1 km) yearly mean concentrations of PM2.5 were predicted from local monitoring data and US National Aeronautics and Space Administration satellite data using linear regression. Baseline residential PM2.5 exposure was used as a proxy for long-term exposure. We used Cox proportional hazards to evaluate the risk of incident stroke associated with PM2.5 exposure adjusted for potential confounders, including individual and neighborhood factors.Results:Over a mean follow-up of 9.4 years, we ascertained 6,733 cases of incident stroke, of which 3,526 (52.4%) were ischemic and 1,175 (17.5%) were hemorrhagic. The hazard ratio for every 10 μg/m3 higher PM2.5 concentration was statistically significant at 1.21 (95% confidence interval [CI] 1.04–1.41) for ischemic and non-statistically significant at 0.90 (95% CI 0.70–1.17) for hemorrhagic stroke in fully adjusted model 3. The estimates for ischemic stroke were higher in older participants (>70 years), less educated participants, and in men for current smokers.Conclusion:Long-term PM2.5 exposure was associated with higher risk of incident ischemic stroke, but the association with incident hemorrhagic stroke was less clear.

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Abstract WP425: Predictive Value Of Daily Physical Activity And New Onset Of Vascular Events In Patients With Mild Ischemic Stroke.

Stroke ◽

10.1161/str.44.suppl_1.awp425 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Yuji Kono ◽

Sumio Yamada ◽

Kenta Kamisaka ◽

Kotaro Iwatsu ◽

Amane Araki ◽

...

Keyword(s):

Physical Activity ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Daily Physical Activity ◽

Stroke Recurrence ◽

Daily Step ◽

Vascular Events ◽

Plaque Score ◽

Step Counts

Introduction: Daily physical inactivity is associated with a substantially increased risk of cardiovascular events. However, the target level of daily physical activity is remained unclear. We aimed to evaluate the impact of physical activity on long-term vascular events in patients with mild ischemic stroke. Methods: We designed prospective observational study and enrolled 142 ischemic stroke patients with modified Rankin Scale 0-1 (mean age: 63.9±9.2). We measured daily step count as a variable of daily physical activity after 6-month from stroke onset. Other clinical characteristics including age, body mass index, blood pressure, blood labo test, carotid echo findings and medications were also assessed. The primary outcome was hospitalization due to stroke recurrence, myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. Results: After 1130.2±372.8 days of follow-up, 29 vascular events (19 stroke recurrence, 10 coronary heart disease) occurred, and the patients were divided into two groups: survival (n=113) and recurrenct (n=29). Daily step counts ( P =0.003) and plaque score ( P <0.001) were significantly lower in the recurrent group than survival group. Univariate and multivariate Cox proportional hazards analysis revealed daily step counts and plaque score to be independent predictors of new vascular events. A daily step counts cutoff value of 6000 steps per day was determined by the analysis of receiver-operating characteristics with sensitivity 69.4% and specificity 79.4%. Kaplan-Meier survival curves after log-rank test showed significantly lower event rate in over 6000 steps group as compared to less than 6000 steps group ( P =0.023). Conclusion: In conclusion, our data indicate that daily physical activity evaluated by step counts may be useful for forecasting prognosis in patients with mild ischemic stroke. Daily step counts of 6000 steps may be a first target level to reduce new vascular events.

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Traffic noise, air pollutants and incidence of diabetes mellitus: a population cohort study in Milan

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.165 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

P Magnoni ◽

R Murtas ◽

A G Russo

Keyword(s):

Diabetes Mellitus ◽

Cohort Study ◽

Proportional Hazards ◽

Traffic Noise ◽

Cox Proportional Hazards ◽

Traffic Intensity ◽

City Center ◽

Increased Risk ◽

Stratified Analysis ◽

The City

Abstract Background Recent evidence suggests a link between long-term exposure to traffic-related pollution and incidence of type 2 diabetes mellitus, a leading cause of morbidity and mortality in adults. The present study aims at exploring this association in a highly urbanized setting such as the city of Milan. Methods This is a population-based retrospective dynamic cohort study in the municipality of Milan. All residents aged >35 years with no prior diagnosis of diabetes were included (N = 1096654), with follow-up ranging from January 2011 to June 2019. The residential address of each subject was geocoded and assigned mean values of traffic noise at the day-evening-night level (Lden, dB) and NO2 concentration (µg/m3) using a noise predictive model and a NO2 land-use regression model with 30x30 m grid resolution. Associations with a new diagnosis of diabetes were assessed with Cox proportional hazards models adjusted for age, sex, nationality and a socio-economic deprivation index. A dichotomous classification of addresses as city center/suburban based on the External Ring Road as a delimiter was also used for a stratified analysis. Results New diagnoses of diabetes occurred in 26134 subjects (2.4%). Models using NO2, either continuous or ranked into quintiles, yielded no significant results. When using noise to categorize traffic intensity (<65/65-69/70-74/≥75 dB), a positive yet non-significant trend was shown. At stratified analysis, increases in risk were found for the two highest levels of exposure in the city center (70-74 dB: HR 1.141, 95% C.I. 1.013-1.284; ≥75 dB: HR 1.185, 95% C.I. 1.058-1.328). Conclusions Residential proximity to high-traffic roads categorized according to traffic noise was found to be associated with an increased risk of being diagnosed with diabetes. The effect is evident in the city center, whereas in the suburban area it might be masked by individual and lifestyle factors that ought to be investigated in future studies. Key messages Living close to high-traffic roads in a highly urbanized environment increases the risk of diabetes. Policies aimed at reducing traffic intensity in large cities may lower the incidence of this highly prevalent chronic condition.

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Serum dickkopf-3 is associated with death and vascular events after ischemic stroke: an observational study from CATIS

Journal of Neuroinflammation ◽

10.1186/s12974-019-1680-4 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Zhengbao Zhu ◽

Daoxia Guo ◽

Chongke Zhong ◽

Aili Wang ◽

Tan Xu ◽

...

Keyword(s):

Ischemic Stroke ◽

Primary Outcome ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Patients ◽

Special Effect ◽

Vascular Events ◽

Cox Proportional Hazards Regression ◽

Net Reclassification Improvement ◽

Proportional Hazards Regression

Abstract Background Dickkopf-3 (Dkk-3) is implicated in the progression of atherosclerosis. This study aimed to investigate the association between serum Dkk-3 and the prognosis of ischemic stroke. Methods We measured serum Dkk-3 levels in 3344 ischemic stroke patients from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of death and vascular events within 3 months after ischemic stroke. Results During 3 months of follow-up, the cumulative incidence rates of primary outcome among ischemic stroke patients in five quintiles of serum Dkk-3 (from low to high) were 4.49%, 3.74%, 2.54%, 5.23%, and 6.73%, respectively (log-rank p = 0.004). Multivariable Cox proportional hazards regression analyses showed that compared with the third quintile of serum Dkk-3, the adjusted hazard ratios (95% confidence intervals) associated with the first and fifth quintile were 3.49 (1.46–8.34) and 4.23 (1.86–9.64) for primary outcome, 3.47 (1.06–11.36) and 5.30 (1.81–15.51) for death, and 2.66 (1.01–7.01) and 3.35 (1.33–8.40) for vascular events, respectively. Multivariable-adjusted Cox proportional hazards regression model with restricted cubic splines showed a U-shaped association between serum Dkk-3 and the risk of primary outcome (p for nonlinearity = 0.030). Moreover, adding serum Dkk-3 to conventional risk factors could improve the predictive power for primary outcome (net reclassification improvement 28.44%, p < 0.001; integrated discrimination improvement 0.48%, p = 0.001). Conclusions Both low and high serum Dkk-3 levels are associated with increased risks of death and vascular events within 3 months after ischemic stroke, indicating that serum Dkk-3 may have a special effect on the prognosis of ischemic stroke. We also found that serum Dkk-3 might be a prognostic biomarker for ischemic stroke. Further studies are needed to replicate our findings and to determine the optimal levels of serum Dkk-3.

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Hemoglobin, Albumin, Lymphocyte, and Platelet Score is Associated With Adverse Clinical Outcomes of Acute Ischemic Stroke: A Prospective Cohort Study

10.21203/rs.3.rs-38304/v1 ◽

2020 ◽

Author(s):

Mengke Tian ◽

Youfeng Li ◽

Xiao Wang ◽

Xuan Tian ◽

Lu-lu Pei ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Recurrence ◽

Vascular Events ◽

Risk Of Death ◽

Clinical Events ◽

Secondary Outcomes

Abstract Background The combined index of hemoglobin, albumin, lymphocyte and platelet (HALP) is considered as a novel score to reflect systemic inflammation and nutritional status. This study aimed to investigate the association between HALP score and adverse clinical events in patients with acute ischemic stroke (AIS). Methods This study prospectively included patients with AIS within 24 hours of admission to the First Affiliated Hospital of Zhengzhou University. The primary outcomes were all-cause death within 90 days and 1 year. The secondary outcomes included stroke recurrence and combined vascular events. The association between HALP score and adverse clinical outcomes was analyzed using Cox proportional hazards. Results A total of 1337 patients were included. Patients in the highest tertile of HALP score had a lower risk of death within 90 days and 1 year (Hazard ratio: 0.20 and 0.30; 95% confidence intervals: 0.06–0.66 and 0.13–0.69, P for trend < 0.01 for all) compared with the lowest tertile after adjusting relevant confounding factors. Similar results were found for secondary outcomes. Subgroup analyses further confirmed these association. Adding HALP score to the conventional risk factors improved prediction of death in patients with AIS within 90 days and 1 year (net reclassification index, 38.63% and 38.68%; integrated discrimination improvement, 2.43% and 2.57%; P < 0.02 for all). Conclusions High HALP score levels were associated with decreased risk of adverse clinical outcomes within 90 days and 1 year after stroke onset, suggesting that HALP score may serve as a powerful indicator for AIS.

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Abstract 74: Obesity and the Risk of Recurrent Vascular Events in Patients with Ischemic Stroke: Insights from the Insulin Resistance Intervention after Stroke (IRIS) Trial

Stroke ◽

10.1161/str.48.suppl_1.74 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jennifer L Dearborn ◽

Catherine M Viscoli ◽

Silvio E Inzucchi ◽

Lawrence H Young ◽

Walter N Kernan

Keyword(s):

Ischemic Stroke ◽

Lower Risk ◽

Proportional Hazards ◽

Cox Model ◽

Recurrent Stroke ◽

Absolute Risk ◽

Cox Proportional Hazards ◽

Metabolic Risk ◽

Obese Patients ◽

Vascular Events

Background: In epidemiologic research, patients with obesity have, on average, a lower risk for recurrent cardiovascular events after ischemic stroke compared with non-obese patients. Despite this “obesity paradox,” we hypothesized that clinical features associated with more severe metabolic disease would identify overweight and obese stroke patients at high risk for recurrent vascular events. Methods: The IRIS trial examined the efficacy of pioglitazone compared with placebo, for prevention of stroke/ myocardial infarction (MI) among non-diabetic insulin resistant patients with a recent ischemic stroke or TIA. Patients were followed for a median of 4.8 years. Among 3,707 participants, we first examined risk of recurrent stroke/MI by obesity status at baseline (overweight or obese [BMI ≥25] vs <25) using Cox proportional hazards models with and without adjustment for sociodemographic factors, smoking and vascular disease history. Next, for 3,142 participants with BMI ≥ 25, a Cox model including 7 baseline features (systolic blood pressure, C-reactive protein, HOMA-IR, hemoglobin A1C, waist circumference, triglycerides and high density lipoprotein) was used to stratify patients into tertiles of “metabolic risk”. The hazard of stroke/MI was then calculated across risk tertiles(T). Results: Overweight and obese participants had a lower incidence of stroke or MI compared with non-obese patients (10.1% vs.12.6%; hazard ratio [HR] 0.77, [0.59-0.99]) and the difference was attenuated after adjustment (HR 0.85 [0.66-1.11]). Among overweight and obese patients, a metabolic risk score identified patients at higher risk of stroke or MI (T3 12.2%, T2 9.2%, T1 9.0%; T3 vs. T1 HR 1.40 [1.08, 1.83]). This association remained significant after adjustments (HR 1.33 [1.02, 1.75]). Conclusion: Although overweight and obese patients may on average have lower risk of recurrent stroke or MI after an ischemic stroke or TIA compared with non-obese individuals, those with advanced metabolic impairment also have a high absolute risk of recurrence.

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Reduced Risks of Both Ischemic and Hemorrhagic Strokes in Nurses: A Population-Based Cohort Study in Taiwan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15122615 ◽

2018 ◽

Vol 15 (12) ◽

pp. 2615

Author(s):

Hui-Chuan Liao ◽

Yi-Hao Peng ◽

Yu-Pei Chen ◽

Li-Chi Huang ◽

Wen-Miin Liang ◽

...

Keyword(s):

Cohort Study ◽

Ischemic Stroke ◽

Lower Risk ◽

Hemorrhagic Stroke ◽

Proportional Hazards ◽

High Stress ◽

Well Being ◽

Cox Proportional Hazards ◽

Control Group ◽

Continuous Variables

Background: Nurses are typically required to address patient emergencies, and they experience high stress levels in their work, which may expose them to a higher risk of stroke. This cohort study compared the risk of stroke between nurses and the general population. Methods: We used the Taiwan National Health Insurance database to conduct our retrospective cohort study, and we identified 83,641 individuals in the nurse group and 334,564 individuals in the control group. For the nurse group and the control group, we used the chi-square test in addition to applying Student’s t-test, in order to compare the distribution differences for the continuous variables. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for ischemic stroke and hemorrhagic stroke through univariate and multivariate Cox proportional-hazards regression models, with stratification according to age, sex, and comorbidity. Results: The nurse group had a lower risk of ischemic stroke and hemorrhagic stroke in the crude model (HR = 0.66, 95% CI = 0.58–0.75; HR = 0.58, 95% CI = 0.47–0.72). After adjusting the prevalent variables, the nurse group still had a lower risk of stroke (HR = 0.68, 95% CI = 0.60–0.77; HR = 0.59, 95% CI = 0.48–0.73). Conclusion: The risks of both stroke types were lower in the nurse group than in the control. For stroke prevention, more frequent physical examinations are needed in order to enhance the health and well-being of people, including the nurses.

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Abstract 151: Vascular Events Occur More Frequently In Stroke Patients With Lower Concentrations of Vitamin D: A Prospective Cohort Analysis

Stroke ◽

10.1161/str.46.suppl_1.151 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Sebastian K Khoo ◽

Jayne Y Tan ◽

Leonard Y Yeo ◽

Prakash Paliwal ◽

Hock L Teoh ◽

...

Keyword(s):

Vitamin D ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Recurrent Stroke ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Hydroxyvitamin D ◽

Cox Proportional Hazards Models ◽

Vitamin D Levels ◽

25 Hydroxyvitamin D

Introduction: Vitamin D deficiency has been implicated in vascular dysfunction and the risk of recurrent vascular events. Previous studies, limited by a small sample size and lack of comparisons with long-term events, have yielded discordant results. To assess the hypothesis that low vitamin D levels predict long-term vascular events in patients with ischemic stroke, we conducted a large hospital-based study to compare the association between baseline vitamin D levels and the subsequent risk of vascular events. Methods: Between January 2010 and July 2011, 590 participants (mean age, 60.7 years; 69% men) diagnosed with ischemic stroke and transient ischemic attack at the National University Hospital, Singapore, were prospectively followed for vascular events (recurrent stroke, myocardial infarction and vascular death). Serum 25-hydroxyvitamin D levels were determined using the Roche Cobas e411 analyzer. Cox proportional hazards models were used to assess the associations between quartiles of serum 25-hydroxyvitamin D and the risk of vascular events, which were adjusted for demographic, stroke severity and subtype, and vascular risk factor covariates. Results: During a mean follow-up of 3.2 years (1,190 person-year), 116 participants developed a recurrent vascular event (recurrent stroke, n=63; myocardial infarction, n=30; vascular death, n=23). Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval) for recurrent vascular events in participants with lower levels of serum 25-hydroxyvitamin D (<14.9 mmol/l, 14.9-21.4 mmol/l and 21.5-28.9 mmol/l) were 1.43 (0.81-2.55), 1.70 (0.97-2.91) and 2.09 (1.22-3.58) compared to participants with higher concentrations (>28.9 mmol/l). Kaplan-Meier plots for unadjusted rates of vascular events show clear differences in risk by quartiles of serum 25-hydroxyvitamin D after a year of follow-up. Conclusions: Our results support the association between vitamin D deficiency and increased risk of recurrent vascular events in patients with ischemic stroke. Clinical trials are needed to ascertain whether correcting for this deficiency could indeed reduce the burden of vascular events in these individuals.

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