Diet and regular soft drinks have been associated with diabetes and the metabolic syndrome, and regular soft drinks with coronary heart disease.
To determine the association between soft drinks and combined vascular events, including stroke.
A population-based cohort study of stroke incidence and risk factors.
Participants (N = 2564, 36% men, mean age 69 ± 10, 20% white, 23% black, 53% Hispanic) were from the Northern Manhattan Study.
We assessed diet and regular soft drink consumption using a food frequency questionnaire at baseline, and categorized: none (<1/month, N = 1948 diet, N = 1333 regular), light (1/month-6/week, N = 453 diet, N = 995 regular), daily (≥1/day, N = 163 diet, N = 338 regular). Over a mean follow-up of 10 years, we examined the association between soft drink consumption and 591 incident vascular events (stroke, myocardial infarction, vascular death) using Cox models.
Controlling for age, sex, race/ethnicity, education, smoking, physical activity, alcohol consumption, BMI, daily calories, consumption of protein, carbohydrates, total fat, saturated fat, and sodium, those who drank diet soft drinks daily (vs. none) had an increased risk of vascular events, and this persisted after controlling further for the metabolic syndrome, peripheral vascular disease, diabetes, cardiac disease, hypertension, and hypercholesterolemia (HR = 1.43, 95% CI = 1.06–1.94). There was no increased risk of vascular events associated with regular soft drinks or light diet soft drink consumption.
Daily diet soft drink consumption was associated with several vascular risk factors and with an increased risk for vascular events. Further research is needed before any conclusions can be made regarding the potential health consequences of diet soft drink consumption.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1968-2) contains supplementary material, which is available to authorized users.
diet; epidemiology; myocardial infarction; stroke; cardiovascular disease
Increased arterial stiffness and wave reflection have been reported in heart failure with normal ejection fraction (HFNEF) and in asymptomatic left ventricular (LV) diastolic dysfunction, a precursor of HFNEF. It is unclear whether women, who have higher frequency of HFNEF, are more vulnerable than men to the deleterious effects of arterial stiffness on LV diastolic function. We investigated in a large community-based cohort, whether sex differences exist in the relationship between arterial stiffness, wave reflection and LV diastolic function. Arterial stiffness and wave reflection were assessed in 983 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study using applanation tonometry. Central pulse pressure/stroke volume index (cPP/SVi), total arterial compliance, pulse pressure amplification and augmentation index were used as parameters of arterial stiffness and wave reflection. LV diastolic function was evaluated by two-dimensional echocardiography and tissue-Doppler imaging. Arterial stiffness and wave reflection were greater in women compared to men, independent of body size and heart rate (all p<0.01), and showed inverse relationships with parameters of diastolic function in both sexes. Further adjustment for cardiovascular risk factors attenuated these relationships; however, higher cPP/SVi predicted LV diastolic dysfunction in women [odds ratio (OR) 1.54, 95% confidence intervals (CI) 1.03–2.30] and men (OR: 2.09, 95% CI 1.30–3.39) independent of other risk factors. In conclusion, in our community-based cohort study, higher arterial stiffness was associated with worse LV diastolic function in men and women. Women’s higher arterial stiffness, independent of body size, may contribute to their greater susceptibility to develop HFNEF.
Arterial stiffness; Wave reflection; Diastole; Sex; Echocardiography
Previous research in our cohort showed a delayed decline in functional status after first ischemic stroke. We compared the long-term trajectory of functional status before and after ischemic stroke.
The Northern Manhattan Study contains a prospective, population-based study of stroke-free individuals >40 years of age, followed for a median 11 years. The Barthel index (BI), a commonly used measure of activities of daily living, was assessed annually. Generalized estimating equations were used to assess functional decline over time before and beginning 6 months after stroke. Follow-up was censored at the time of recurrent stroke.
Among 3298 participants, 210 had an ischemic stroke during follow-up and had post-stroke BI assessed. Mean age (+standard deviation) was 77+9 years, 38% were male, 52% were Hispanic, 37% had diabetes, and 31% had coronary artery disease. There was no difference in rate of functional decline over time before and after stroke (p=0.51), with a decline of 0.96 BI points per year before stroke (p<.0001) and 1.24 after stroke (p=0.001). However, when stratified by insurance status, among those with Medicaid or no insurance, in a fully adjusted model, there was a difference in slope before and after stroke (p=0.04), with a decline of 0.58 BI points per year before stroke (p=0.02) and 1.94 after stroke (p=0.001).
In this large, prospective, population-based study with long-term follow-up, there was a significantly steeper decline in functional status after ischemic stroke compared to before stroke among those with Medicaid or no insurance, after adjusting for confounders.
Epidemiology; Disability; Rehabilitation
Recent studies have suggested poor quality and diminished quantity of sleep may be independently linked to vascular events, though prospective and multiethnic studies are limited. This study aimed to explore the relationship between daytime sleepiness and the risk of ischemic stroke and vascular events in an elderly, multi-ethnic prospective cohort.
Methods and Results
As part of the Northern Manhattan Study, the Epworth Sleepiness Scale (ESS) was collected during the 2004 annual follow-up. Daytime sleepiness was trichotomized using previously reported cut points of “no dozing,” “some dozing,” and “significant dozing”. Subjects were followed annually for a mean of 5.1 years. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for stroke, MI and death outcomes. We obtained the ESS on 2088 community residents. The mean age was 73.5 ± 9.3 yrs; 64% were women; 17% white, 20% black, 60% Hispanic, and 3% other. Over 44% of the cohort reported no daytime dozing, 47% reported “some dozing” and 9% “significant daytime dozing.” Compared to those reporting no daytime dozing, individuals reporting significant dozing had an increased risk of ischemic stroke [HR=2.74 (95% CI 1.38-5.43)], all 6 stroke [3.00 (1.57-5.73)], the combination of ischemic stroke, MI and vascular death [2.38 (1.50-3.78)], and all vascular events [2.48 (1.57-3.91)], after adjusting for medical comorbidities.
Daytime sleepiness is an independent risk factor for stroke and other vascular events. These findings suggest the importance of screening for sleep problems at the primary care level.
Ischemic Stroke; Sleep; Epidemiology; Vascular Disease; race/ethnicity
It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.
We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause.
The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82).
Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.
Carotid plaque is a marker of subclinical atherosclerosis with a genetic component. The aim of this follow-up fine mapping study was to identify candidate genes for carotid plaque within four linkage regions.
We successfully genotyped 3,712 single nucleotide polymorphisms (SNPs) under the four linkage regions that were previously identified in 100 extended Dominican families. Family-based association tests were performed to investigate their associations with carotid plaque. Promising SNPs were evaluated in an independent population-based subcohort (N=941, 384 Dominicans) from the Northern Manhattan Study (NOMAS).
In the family study, evidence for association (p<0.0005) was found regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p=0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p≤0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p=0.00008~0.00001 and 0.76~0.32, respectively, in the families with and without linkage evidence). However, these associations explained only a small portion of the observed linkage. In NOMAS, replication (p<0.05 in the whole NOMAS subcohort and p<0.10 in the smaller Dominican subcohort) was found for SNPs within/near EFCAB11, NAV2, AGBL1 and other genes.
This follow-up study has identified multiple candidate genes for carotid plaque in the Dominican population. Many of these genes have been implicated in neurodegenerative and cardiovascular diseases. Further studies with in-depth re-sequencing are needed to uncover both rare and common functional variants that contribute to the susceptibility to atherosclerosis.
Carotid plaque; Linkage; Fine mapping; Atherosclerosis; Hispanics
Prior studies have reported that Hispanics have lower cardiovascular disease (CVD) mortality despite a higher burden of risk factors. We examined whether Hispanic ethnicity was associated with a lower risk of nonfatal myocardial infarction (MI) coronary death (CD) and vascular death.
A total of 2671 participants in the Northern Manhattan Study without clinical CVD were prospectively evaluated. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of race–ethnicity with nonfatal MI, CD, and vascular death after adjusting for demographic and CVD risk factors.
Mean age was 68.8 (10.4) years; 52.8% were Hispanic (88% Caribbean-Hispanic). Hispanics were more likely to have hypertension (73.1% vs. 62.2%, p < .001) and diabetes (22.0% vs. 13.3%, p < .001), and less likely to perform any physical activity (50.1% vs. 69.2%, p < .001) compared to non-Hispanic whites (NHW). During a mean 10 years of follow-up there were 154 nonfatal MIs, 186 CD, and 386 vascular deaths. In fully adjusted models, Hispanics had a lower risk of CD (adjusted HR = 0.36, 95% CI: 0.21–0.60), and vascular death (adjusted HR = 0.62, 95% CI: 0.43–0.89), but not nonfatal MI (adjusted HR = 0.95, 95% CI: 0.56–1.60) when compared to NHW.
We found a “Hispanic paradox” for coronary and vascular deaths, but not nonfatal MI.
Hispanic; Paradox; Mortality; Cardiovascular Disease
The aim of our study is to determine the association between the pulsatility index (PI), a surrogate of cerebral small vessel disease and sleep-disordered breathing (SDB).
We conducted a transcranial Doppler ultrasound (TCD) study of 19 consecutive patients free of stroke and cardiovascular disease, referred for the evaluation of SDB. TCD was performed by a certified technologist. Subsequent polysomnography was performed according to the practice parameters of the American Academy of Sleep Medicine. We evaluated the association between the apnea–hypopnea index (AHI), the oxygen nadir, the blood flow velocities, and the Gosling PI, for the middle cerebral artery. We performed Spearman’s rank correlation and nonparametric regression to evaluate the relationship between AHI, oxygen levels, and the PI.
Median age was 48 years (range 37–83), with 52 % male sex (n=10), and median BMI of 29.9 (range 25–40.4). The median AHI was 16.4 (0.2–69). The median PI was 0.97 (0.72–1.89) cm/s. The PI correlated with the AHI (rho=0.44; p=0.004) and with age (rho=0.57; p=0.001). Nonparametric regression adjusting for age showed a positive association between the AHI and the PI (standardized estimate=0.88; p=0.002). There was no relation between the oxygen nadir and the PI.
We observed increased PI in patients with SDB during wakefulness. The PI could potentially be an estimate of cerebral small vessel disease in patients with SDB and hence allow evaluating cerebral hemodynamics during wakefulness with a clinically relevant device.
Transcranial Doppler; Sleep-disordered breathing; Pulsatility index; Stroke; Microvascular disease
Background and Purpose
Diabetes increases stroke risk, but whether diabetes status immediately prior to stroke improves prediction, and whether duration is important, are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke.
Among 3,298 stroke-free participants in the Northern Manhattan Study (NOMAS), baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median=9 years). Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals (HR, 95% CI) for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors.
Mean age was 69±10 years (52% Hispanic, 21% white, and 24% black); 22% were diabetic at baseline and 10% developed diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR 2.5, 95% CI 1.9-3.3) and diabetes considered as a time-dependent covariate (HR 2.4, 95% CI 1.8-3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR=1.03 per year with diabetes, 95% CI=1.02-1.04). Compared to non-diabetic participants, those with diabetes for 0-5 years (adjusted HR=1.7, 95% CI=1.1-2.7), 5-10 years (adjusted HR=1.8, 95% CI=1.1-3.0), and ≥10 years (adjusted HR=3.2, 95% CI=2.4-4.5) were at increased risk.
Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥10 years.
Diabetes mellitus; ischemic stroke; epidemiology; risk factors
Background and purpose
The American Heart Association (AHA) recommends limiting sodium intake to ≤1500 mg/day for ideal cardiovascular health. Although sodium intake has been linked to vascular disease by direct relationship with hypertension, few studies have supported an association with stroke risk.
Participants were from the Northern Manhattan Study (mean age 69±10 years, 64% women, 21% white, 53% Hispanic, 24% black), a population-based cohort study of stroke incidence. Sodium intake was assessed with a food frequency questionnaire at baseline and evaluated continuously and categorically: ≤1500 mg/day (12%), 1501–2300 mg/day (24%), 2301–3999 mg/day (43%), ≥4000 mg/day (21%). Over a mean follow-up of 10 years we examined the association between sodium consumption and 235 strokes using Cox models, adjusting for sociodemographics, diet, behavioral/lifestyle and vascular risk factors.
Of 2657 participants with dietary data, the mean sodium intake was 3031±1470 mg/day, median 2787 (IQR 1966–3815) mg/day. Participants who consumed ≥4000 mg/day sodium had an increased risk of stroke (HR=2.59; 95% CI=1.27–5.28) vs. those who consumed ≤1500 mg/day, with a 17% increased risk of stroke for each 500 mg/day increase (95% CI=1.07–1.27).
High sodium intake was prevalent and associated with an increased risk of stroke independent of vascular risk factors. The new AHA dietary sodium goals will help reduce stroke risk.
sodium; stroke; diet; epidemiology
Atherosclerotic plaque in the aortic arch is an independent risk factor for ischemic stroke. Although high blood pressure (BP) measured at the doctor’s office is known to be associated with aortic atherosclerosis, little is known on the association between 24-hour ambulatory BP and aortic arch plaque presence and severity. Our objective was to clarify the association between ambulatory BP variables and aortic arch atherosclerosis in a community-based cohort.
The study population consisted of 795 patients (mean age 71±9 years) participating in the Cardiovascular Abnormalities and Brain Lesions (CABL) study who underwent 24-hour ambulatory BP monitoring (ABPM). Arch plaque was evaluated by 2D transthoracic echocardiography from a suprasternal window.
All systolic ABPM variables (24-hour/daytime/nighttime mean systolic BP, daytime/nighttime systolic BP variability) were associated with the presence of any plaque and large (≥4mm) plaque, whereas diastolic BP variables were not associated with aortic atherosclerosis. Multiple regression analysis indicated that nighttime systolic BP variability (expressed as the standard deviation of nighttime systolic BP) remained independently associated with large plaque after adjustment for age, sex, cigarette smoking, history of hypertension, diabetes mellitus, hypercholesterolemia, anti-hypertensive medication and nighttime mean systolic BP (odds ratio 1.39 per 1 standard deviation increase, 95% CI 1.00 to 1.93, P<0.05).
Systolic ABPM variables are significantly associated with the presence of arch plaque. Nighttime systolic BP variability is independently associated with large arch plaque. These findings may have important implications in gaining further insights into the mechanism of arch plaque formation and progression.
ambulatory blood pressure; aortic arch atherosclerosis; blood pressure variability
Background and purpose
Adiponectin is an insulin-sensitizing plasma protein expressed in adipose tissue and suggested to play a role in atherosclerosis and cardiovascular disease. Data are lacking on the relationship between adiponectin and carotid intima-media thickness (IMT) in ethnically heterogeneous populations. We examined the relationship between adiponectin and IMT, a marker of atherosclerosis, in a multi-ethnic cohort study of stroke risk factors.
Participants were from the Northern Manhattan Study (N=1522, mean age 66±9 years, 60% female, 20% black, 18% white, 60% Hispanic). Adiponectin was measured from baseline plasma samples and IMT was assessed by high-resolution B-mode carotid ultrasound. Regression models were used to examine the association between adiponectin, assessed continuously and in quartiles, and IMT, controlling for demographics and vascular risk factors.
The mean adiponectin level was 10.3±5.2 μg/ml (median=9.2, range=2.3-53.3), and the mean IMT was 0.91±0.08 mm. Adiponectin was inversely associated with IMT, even after controlling for demographics and vascular risk factors. Individuals in the first quartile of adiponectin had mean IMT that was on average 0.02 mm greater than those in the top quartile. The relationship between adiponectin and IMT appeared to be stronger among those with diabetes.
Our findings suggest that low adiponectin is associated with increased IMT in a multi-ethnic cohort and support a protective role for adiponectin in atherosclerosis.
Adiponectin; carotid artery; intima-media thickness; atherosclerosis; epidemiology
Carotid intima-media thickness (CIMT) is a subclinical measure for atherosclerosis. Previously, we have mapped quantitative trait loci (QTLs) for CIMT to chromosomes 7p (MLOD=3.1) and to 14q (MLOD=2.3). We sought to identify the underlying genetic variants within those QTLs,
Methods and Results
Using the 100 extended Dominican Republican (DR) families (N=1312) used in the original linkage study, we fine mapped the QTLs with 2031 tagging single nucleotide polymorphisms (SNPs). Promising SNPs in the family dataset were examined in an independent population-based subcohort comprised of DR individuals (N=553) from the Northern Manhattan Study. Among the families, evidence for association (P<0.001) was found in multiple genes (ANLN, AOAH, FOXN3, CCDC88C, PRiMA1, and an intergenic SNP rs1667498), with the strongest association at PRiMA1 (P=0.00007, corrected P=0.047). Additional analyses revealed that the association at these loci, except PRiMA1, was highly significant (P= 0.00004~0.00092) in families with evidence for linkage but not in the rest of families (P=0.13~0.80) and the population-based cohort, suggesting the genetic effects at these SNPs are limited to a subgroup of families. In contrast, the association at PRiMA1 was significant in both families with and without evidence for linkage (P=0.002 and 0.019, respectively), and the population-based subcohort (P=0.047), supporting a robust association.
We identified several candidate genes for CIMT in DR families. Some of the genes manifest genetic effects within a specific subgroup and others were generalized to all groups. Future studies are needed to further evaluate the contribution of these genes to atherosclerosis.
By the year 2010, it is estimated that 18.1 million people worldwide will die annually because of cardiovascular diseases and stroke. “Global vascular risk” more broadly includes the multiple overlapping disease silos of stroke, myocardial infarction, peripheral arterial disease, and vascular death. Estimation of global vascular risk requires consideration of a variety of variables including demographics, environmental behaviors, and risk factors. Data from multiple studies suggest continuous linear relationships between the physiological vascular risk modulators of blood pressure, lipids, and blood glucose rather than treating these conditions as categorical risk factors. Constellations of risk factors may be more relevant than individual categorical components.
Exciting work with novel risk factors may also have predictive value in estimates of global vascular risk. Advances in imaging have led to the measurement of subclinical conditions such as carotid intima-media thickness and subclinical brain conditions such as white matter hyperintensities and silent infarcts. These subclinical measurements may be intermediate stages in the transition from asymptomatic to symptomatic vascular events, appear to be associated with the fundamental vascular risk factors, and represent opportunities to more precisely quantitate disease progression. The expansion of studies in molecular epidemiology and detection of genetic markers underlying vascular risks also promises to extend our precision of global vascular risk estimation.
Global vascular risk estimation will require quantitative methods that bundle these multi-dimensional data into more precise estimates of future risk. The power of genetic information coupled with data on demographics, risk-inducing behaviors, vascular risk modulators, biomarkers, and measures of subclinical conditions should provide the most realistic approximation of an individual's future global vascular risk. The ultimate public health benefit, however, will depend on not only identification of global vascular risk but also the realization that we can modify this risk and prove the prediction models wrong.
cerebrovascular disease; epidemiology; prevention; risk factors
Background and Purpose
There is scant population-based evidence regarding extracranial carotid plaque surface irregularity and ischemic stroke. Using a prospective cohort design, we evaluated the association of carotid plaque surface irregularity and the risk of ischemic stroke in a multiethnic population.
High-resolution B-mode ultrasound of the carotid arteries was performed in 1939 stroke-free subjects (mean age 69±10.0 years; 59% women; 53% Hispanic, 25% black, 22% white). Plaque was defined as a focal protrusion 50% greater than the surrounding area and localized along the extracranial carotid tree (internal carotid artery/bifurcation vs common carotid artery). Plaque surface was categorized as regular or irregular. Cox proportional hazard models were used to assess the association of surface characteristics and the risk of ischemic stroke.
Among 1939 total subjects, carotid plaque was visualized in 56.3% (1 plaque: 21.6%, >1 plaque: 34.7%, irregular plaque: 5.5%). During a mean follow up of 6.2 years after ultrasound examination, 69 ischemic strokes occurred. Unadjusted cumulative 5-year risks of ischemic stroke were: 1.3%, 3.0%, and 8.5% for no plaque, regular plaque, and irregular plaque, respectively. After adjusting for demographics, traditional vascular risk factors, degree of stenosis, and plaque thickness, presence of irregular plaque (vs no plaque) was independently associated with ischemic stroke (Hazard ratio, 3.1; 95% CI, 1.1 to 8.5).
The presence of irregular carotid plaque independently predicted ischemic stroke in a multiethnic cohort. Plaque surface irregularities assessed by B-mode ultrasonography may help identify intermediate- to high-risk individuals beyond their vascular risk assessed by the presence of traditional risk factors.
carotid artery; irregular plaque; stroke; ultrasound
The meanings of several target neuropsychological variables, including measures of executive functioning, were examined using contextual analysis across a sample of English-speakers and a sample of Spanish-speakers. Results of the contextual analysis, which examined the contributions of the latent constructs of memory, psychomotor speed, visual spatial ability, and knowledge and comprehension, to the target neuropsychological variables indicate that each of the target variables likely reflects the unique contribution of several reference abilities. These findings provide evidence that the neuropsychological variables are multi-dimensional. The patterns of relations were similar across the samples of English and Spanish speakers.
contextual analysis; executive functioning; memory; psychomotor speed; structural equation modeling; race; ethnicity; vascular cognitive impairment
Background and Purpose
Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent non-cardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality.
The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age and sex matched stroke patients without SBI. Secondary outcomes were a combined vascular endpoint, other vascular events and mortality. The two groups were compared using conditional logistic regression.
Silent brain infarction was detected in 207 (20.4%) patients of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (odds ratio 1.42, 95% confidence interval 0.79 to 2.56; p=0.24) during a mean follow-op of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI.
The presence of SBI in patients with recent mild non-cardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality.
Cerebral infarction; silent brain infarction; ischemic stroke; magnetic resonance imaging; mortality
To examine the association between a Mediterranean-style diet (MeDi) and brain MRI white matter hyperintensities (WMH). The MeDi has previously been associated with a reduced risk of cardiovascular morbidity, possibly including stroke. A greater understanding of modifiable risk factors for small vessel damage may facilitate the prevention of stroke and cognitive decline.
A cross-sectional analysis within a longitudinal population-based cohort study. A semi-quantitative food frequency questionnaire was administered and a score (range 0-9) was calculated to reflect increasing similarity to the MeDi pattern.
The Northern Manhattan Study.
1,091 participants, of which 966 had dietary information (mean age 72, 59% women, 65% Hispanic, 16% White, 17% Black).
Main outcome measures
WMH volume was measured by quantitative brain MRI. Linear regression models were constructed to examine the relation between the MeDi score and the log-transformed WMH volume as a proportion of total cranial volume, controlling for sociodemographic and vascular risk factors.
On the MeDi scale, 12% scored 0-2, 16 scored 3, 23% scored 4, 23% scored 5, 26% scored 6-9. Each 1-point increase in MeDi score was associated with a lower log WMH volume (β=-0.04, p=0.02). The only MeDi score component that was an independent predictor of WMH volume was the ratio of monounsaturated to saturated fat (β=-0.20, p=0.001).
A Mediterranean-style diet was associated with a lower WMH burden, a marker of small vessel damage in the brain. However, white matter hyperintensities are etiologically heterogenous and can include neurodegeneration. Replication by other population-based studies is needed.
The metabolic syndrome (MetS) is a risk factor for diabetes, stroke, myocardial infarction, and increased mortality, and has been associated with cognition in some populations. We hypothesized that MetS would be associated with lower Mini-Mental State Examination (MMSE) scores in a multi-ethnic population, and that MetS is a better predictor of cognition than its individual components or diabetes.
We conducted a cross-sectional analysis among 3,150 stroke-free participants. MetS was defined by the modified National Cholesterol Education Program guidelines-Adult Treatment Panel III (NCEP-ATPIII) criteria. Linear regression and polytomous logistic regression estimated the association between MMSE score and MetS, its individual components, diabetes, and inflammatory biomarkers.
MetS was inversely associated with MMSE score (unadjusted β = −0.67; 95% CI −0.92, −0.41). Adjusting for potential confounders, MetS was associated with lower MMSE score (adjusted β = −0.24; 95% CI −0.47, −0.01), but its individual components and diabetes were not. Those with MetS were more likely to have an MMSE score of <18 than a score of ≥24 (adjusted OR = 1.94; 95% CI 1.26, 3.01). There was an interaction between MetS and race-ethnicity, such that MetS was associated with lower MMSE score among non-Hispanic whites and Hispanics but not non-Hispanic blacks.
MetS was associated with lower cognition in a multi-ethnic population. Further studies of the effect of MetS on cognition are warranted, and should account for demographic differences.
Cognitive performance; Cognitive impairment; Vascular dementia; Vascular cognitive impairment; Cerebrovascular disorders; Metabolic syndrome
Background and Purpose
Few studies have examined the early effects of statins on carotid artery elasticity, a potential surrogate marker of cardiovascular risk. This study examined the short-term effects of atorvastatin 80 mg daily on carotid elasticity measured by high resolution B-mode ultrasound.
The study included 40 stroke-free and statin-naïve subjects over age 45 (mean age 70±7 years; 55% men; 64% Caribbean-Hispanic). Outcome measures included carotid stiffness indices at 14 and 30 days after initiation of treatment. The systolic (SD) and diastolic (DD) diameters of the right common carotid artery were averaged from multiple B-mode imaging frames. Absolute and relative changes of Strain [(SD-DD)/DD], Stiffness (β) [ln (systolic/diastolic blood pressure)/strain] and distensibility (1/β adjusted for wall thickness) from baseline were compared by the repeated measures t-test and considered significant at α of 0.05.
Baseline mean stiffness was 0.08 (95% CI: 0.06–0.10). It significantly decreased at Day 30 to 0.05 (CI: 0.04–0.06; p<0.01). Mean baseline distensibility was 15.25 [CI: 13.18–17.32], increasing significantly at Day 30 to 17.23 [CI: 14.01–20.45, p<0.05]. An improvement in distensibility of ≥ 10% from baseline was observed in 29 (73%) subjects. Changes in stiffness and distensibility were maximal among subjects with baseline low-density lipoprotein (LDL) levels <130 mg/dL.
Short-term treatment with high-dose atorvastatin was associated with improvement in the carotid elasticity metrics. Carotid artery elasticity measured by B-mode ultrasound is a simple non-invasive measure of arterial wall function and may be a useful surrogate endpoint in clinical trials targeting individuals at increased risk for atherosclerosis.
statins; carotid arteries; elasticity; carotid ultrasound
Race/ethnic differences in carotid arterial function and structure exist among those with cerebrovascular disease, but whether differences persist among healthy populations is unknown. Our objective was to investigate differences in carotid artery diameter and stiffness between race/ethnic groups, and examine whether these race/ethnic differences were age-dependent.
Carotid diameters were assessed by B-mode ultrasound among 1536 participants from the Northern Manhattan Study (NOMAS), and carotid stiffness metrics were calculated. We used multivariable linear regression models to determine the relationship between race/ethnicity and both carotid arterial stiffness and carotid diastolic diameter.
Mean participant age was 70 ± 9 years (Hispanics=68 ± 8, blacks=72 ± 9, and whites=74 ± 9, p<0.0001). Mean DDIAM was 6.2 ± 1.0mm (Hispanics=6.2 ± 0.9mm, blacks=6.3 ± 1.0mm, and whites=6.3 ± 1.0mm, p<0.005) and mean STIFF was 8.7 ± 6.3 (Hispanics=8.5 ± 5.7, blacks=9.2 ± 6.2 and whites=8.9 ± 6.9, p<0.02). In a model that adjusted for sociodemographics and vascular risk factors including hypertension, diabetes, dislipidemia, renal function, physical acticity and a history of known coronary artery diseases; age was positively associated with greater DDIAM in Hispanics (p<0.0001) but not among blacks or whites. Older age was associated with greater stiffness among Hispanics (p<0.0001) and blacks (p<0.003), but not among whites.
We found race/ethnic differences in the association between age and arterial stiffness and diameter, including age-dependent arterial dilation observed in Hispanics that was not observed among blacks or whites.
arterial stiffness; atherosclerosis; diastolic diameter; carotid artery; race/ethnicity; carotid ultrasound
The relationship between alcohol consumption and ischemic stroke or aortic atherosclerosis is unclear, but a protective effect of moderate consumption on stroke risk has been suggested. We conducted a cross-sectional analysis in a population-based sample to evaluate the possible association between alcohol consumption and aortic atherosclerotic plaque (AAP), which is associated with increased stroke risk.
As part of the NINDS-funded Aortic Plaques and Risk of Ischemic Stroke (APRIS) study, 464 subjects over the age of 55 were studied (mean age 69.1±9.0 with 251 males and 213 females), including 255 patients with first ischemic stroke and 209 stroke-free controls. Transesophageal echocardiogram was performed for the detection of AAP. Alcohol consumption was measured in number of drinks per week during the previous year using a standardized questionnaire, and categorized as: (1) none or minimal (<1 drink per month); (2) light to moderate (between 1 drink per month and 2 drinks daily); and (3) heavy (>2 daily). Multivariate conditional logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence interval (CI) for alcohol consumption and AAP after adjustment for the potential confounding risk factors (age, sex, hypertension, diabetes, dyslipidemia, and cigarette smoking).
Overall, AAP were detected in 326 subjects (70.4%), and 174 subjects (37.6%) had AAP ≥ 4mm, which carry higher stroke risk. No or minimal alcohol consumption was present in 241 subjects (53.2%), and 177 subjects (39.0%) had light to moderate consumption. Prevalence of light to moderate alcohol consumption was significantly lower in stroke patients than in controls (35.5% vs. 60.3%, p<0.001) and in subjects who had AAP compared with those without it (41.6% vs. 58.8%, p=0.008). After adjusting for significant predictors of atherosclerosis, alcohol consumption of any degree was inversely associated with AAP (OR 0.61; 95%CI 0.37–0.98, p=0.042). The significance of the association was borderline for AAP ≥ 4mm (OR 0.64, 95%CI 0.41–1.00, p=0.054). In the dose-response analysis, only light to moderate alcohol consumption was significantly associated with a lower risk of having any AAP (adjusted OR 0.45; 95%CI 0.29–0.68, p<0.001) or AAP ≥ 4mm (adjusted OR 0.51; 95%CI 0.34–0.77, p=0.001).
Our data indicate that light to moderate alcohol consumption is associated with lower atherosclerotic burden in the proximal aortic arch. This observation may explain at least in part the lower risk of ischemic stroke observed in moderate alcohol consumers.
aorta; atherosclerosis; stroke; alcohol drinking; risk factors
Sleep disorders are associated with stroke and may vary among elderly Hispanics, Blacks and Whites. We evaluated differences in sleep symptoms by race-ethnicity in an elderly population-based urban community sample.
Snoring, daytime sleepiness and reported sleep duration were ascertained by standardized interviews as a part of the Northern Manhattan Study, a prospective cohort study of vascular risk factors and stroke risk in a multi-ethnic urban population. Sleep symptoms were compared amongst race-ethnic groups using logistic regression models.
A total of 1,964 stroke-free participants completed sleep questionnaires. The mean age was 75 ± 9 years, with 37% men, with 60% Hispanics, 21% Blacks and 19% Whites. In models adjusted for demographic and vascular risk factors, Hispanics had increased odds of frequent snoring (odds ratio, OR: 3.6, 95% confidence interval, CI: 2.3–5.8) and daytime sleepiness (OR: 2.8, 95% CI: 1.7–4.5) compared to White participants. Hispanics were more likely to report long sleep (≥9 h of sleep, OR: 1.8, 95% CI: 1.1–3.1). There was no difference in sleep symptoms between Black and White participants.
In this cross-sectional analysis among an elderly community cohort, snoring, sleepiness and long sleep duration were more common in Hispanics. Sleep symptoms may be surrogate markers for an underlying sleep disorder which may be associated with an elevated risk of stroke and may be modified by clinical intervention.
Sleep symptoms; Snoring; Sleepiness; Sleep duration; Race; Ethnicity
Background and Purpose
The Framingham coronary heart disease (CHD) risk score (FRS) estimates 10-year risk of myocardial infarction (MI) and CHD death. Since preventive approaches to CHD and stroke are similar, a composite outcome may be more appropriate. We compared 10-year risk of 1) MI or CHD death, and 2) stroke, MI, or CHD death, among individuals free of vascular disease.
The Northern Manhattan Study contains a prospective, population-based study of stroke- and CHD-free individuals ≥40 years of age, followed for a median of 10 years for vascular events. FRS was calculated for each individual, and for each category of predicted risk, Kaplan-Meier observed 10-year cumulative probabilities were calculated for 1) MI or CHD death and 2) stroke, MI, or CHD death. The cumulative probability of (1) was subtracted from (2), and 95% confidence intervals (CI) for the difference were obtained with 1000 bootstrap samples. Using stratified analyses by race-ethnicity, we compared risk differences between race-ethnic groups.
Among 2613 participants (53% Hispanic, 25% non-Hispanic black and 20% non-Hispanic white), observed 10-year risk of MI or CHD death was 14.20%. With stroke in the outcome, observed risk was 21.98% (absolute risk difference 7.78%, 95% CI 5.86-9.75%). The absolute risk difference among blacks was significantly larger than among whites (p=0.01).
In this multi-ethnic urban population, adding stroke to the risk stratification outcome cluster resulted in a 55% relative increase in estimated risk, and crossing of the absolute risk threshold (>20% over 10 years) considered for preventive treatments such as statins.
Epidemiology; Stroke Management; Risk Factors
Assess the association of vitamin D deficiency and indices of mineral metabolism with subclinical carotid markers that predict cardiovascular events.
203 community-dwelling adults (Northern Manhattan Study, age: 68±11, 50–93 yrs) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D [25OHD], 1,25-dihydroxyvitamin D, PTH) and carotid ultrasound (plaque presence, number, maximal carotid plaque thickness [MCPT], intima-media thickness [IMT]).
Adjusting for cardiovascular risk factors, plaque number was associated with phosphorus levels (β=0.39 per unit increase; p=0.02) and calcium-phosphorus product (β=0.36 per 10 unit increase; p=0.03). In those with plaque (N=116; 57%), the association of plaque number with phosphorus and calcium-phosphorus product persisted. In addition, 25OHD was inversely associated with both IMT (β= −0.01 per 10 ng/ml increase; p=0.05) and MCPT (β= −0.10 per 10 ng/ml increase; p=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25OHD accounted for 13% of the variance in both IMT and MCPT. Calcium, PTH, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures.
After adjusting for cardiovascular risk factors and renal function, serum phosphorus and calcium-phosphorus product were associated with greater burden of subclinical carotid atherosclerosis. Low 25OHD levels were associated with increased IMT and MCPT in those with plaque, and 25OHD contributed in a robust manner to the variance in both. These results confirm and extend data on the association of low vitamin D levels with subclinical carotid atherosclerosis. The precise nature of this association and the optimum levels of vitamin D for vascular health remain to be elucidated.
Vitamin D deficiency; parathyroid hormone; carotid plaque; IMT; atherosclerosis