Hannah Gardener

Prenatal risk factors for autism: comprehensive meta-analysis

BACKGROUND The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years. AIMS To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism. METHOD PubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies. RESULTS Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling. CONCLUSIONS There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.

Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study

BACKGROUND A dietary pattern common in regions near the Mediterranean appears to reduce risk of all-cause mortality and ischemic heart disease. Data on blacks and Hispanics in the United States are lacking, and to our knowledge only one study has examined a Mediterranean-style diet (MeDi) in relation to stroke. OBJECTIVE In this study, we examined an MeDi in relation to vascular events. DESIGN The Northern Manhattan Study is a population-based cohort to determine stroke incidence and risk factors (mean ± SD age of participants: 69 ± 10 y; 64% women; 55% Hispanic, 21% white, and 24% black). Diet was assessed at baseline by using a food-frequency questionnaire in 2568 participants. A higher score on a 0-9 scale represented increased adherence to an MeDi. The relation between the MeDi score and risk of ischemic stroke, myocardial infarction (MI), and vascular death was assessed with Cox models, with control for sociodemographic and vascular risk factors. RESULTS The MeDi-score distribution was as follows: 0-2 (14%), 3 (17%), 4 (22%), 5 (22%), and 6-9 (25%). Over a mean follow-up of 9 y, 518 vascular events accrued (171 ischemic strokes, 133 MIs, and 314 vascular deaths). The MeDi score was inversely associated with risk of the composite outcome of ischemic stroke, MI, or vascular death (P-trend = 0.04) and with vascular death specifically (P-trend = 0.02). Moderate and high MeDi scores were marginally associated with decreased risk of MI. There was no association with ischemic stroke. CONCLUSIONS Higher consumption of an MeDi was associated with decreased risk of vascular events. Results support the role of a diet rich in fruit, vegetables, whole grains, fish, and olive oil in the promotion of ideal cardiovascular health.

Improving global vascular risk prediction with behavioral and anthropometric factors: the multiethnic NOMAS (Northern Manhattan Cohort Study).

OBJECTIVES This study sought to improve global vascular risk prediction with behavioral and anthropometric factors. BACKGROUND Few cardiovascular risk models are designed to predict the global vascular risk of myocardial infarction, stroke, or vascular death in multiethnic individuals, and existing schemes do not fully include behavioral risk factors. METHODS A randomly derived, population-based, prospective cohort of 2,737 community participants free of stroke and coronary artery disease was followed up annually for a median of 9.0 years in the NOMAS (Northern Manhattan Study) (mean age 69 years, 63.2% women, 52.7% Hispanic, 24.9% African American, and 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criteria. Model utility was assessed through receiver-operating characteristics, calibration, and effect on reclassification of subjects. RESULTS Variables that significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten-year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10-year event rates compared with a model restricted to the traditional variables. CONCLUSIONS A GVRS that combines traditional, behavioral, and anthropometric risk factors; uses continuous variables for physiological parameters; and is applicable to nonwhite subjects could improve primary prevention strategies.

Dietary Sodium and Risk of Stroke in the Northern Manhattan Study

Background and Purpose— The American Heart Association 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. Methods— 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 to 2300 mg/day (24%), 2301 to 3999 mg/day (43%), and ≥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. Results— Of 2657 participants with dietary data, the mean sodium intake was 3031±1470 mg/day (median, 2787; interquartile range, 1966–3815 mg/day). Participants who consumed ≥4000 mg/day sodium had an increased risk of stroke (hazard ratio, 2.59; 95% CI, 1.27–5.28) versus 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). Conclusions— High sodium intake was prevalent and associated with an increased risk of stroke independent of vascular risk factors. The new American Heart Association dietary sodium goals will help reduce stroke risk.

Clinical ResearchCardiovascular RiskImproving Global Vascular Risk Prediction With Behavioral and Anthropometric Factors: The Multiethnic NOMAS (Northern Manhattan Cohort Study)

OBJECTIVES This study sought to improve global vascular risk prediction with behavioral and anthropometric factors. BACKGROUND Few cardiovascular risk models are designed to predict the global vascular risk of myocardial infarction, stroke, or vascular death in multiethnic individuals, and existing schemes do not fully include behavioral risk factors. METHODS A randomly derived, population-based, prospective cohort of 2,737 community participants free of stroke and coronary artery disease was followed up annually for a median of 9.0 years in the NOMAS (Northern Manhattan Study) (mean age 69 years, 63.2% women, 52.7% Hispanic, 24.9% African American, and 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criteria. Model utility was assessed through receiver-operating characteristics, calibration, and effect on reclassification of subjects. RESULTS Variables that significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten-year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10-year event rates compared with a model restricted to the traditional variables. CONCLUSIONS A GVRS that combines traditional, behavioral, and anthropometric risk factors; uses continuous variables for physiological parameters; and is applicable to nonwhite subjects could improve primary prevention strategies.

Traditional cardiovascular risk factors explain the minority of the variability in carotid plaque

Background and Purpose— Subclinical atherosclerotic plaque is an important marker of increased vascular risk. Identifying factors underlying the variability in burden of atherosclerotic carotid plaque unexplained by traditional vascular risk factors may help target novel preventive strategies. Methods— As a part of the carotid substudy of the Northern Manhattan Study (NOMAS), 1790 stroke-free individuals (mean age, 69±9; 60% women; 61% Hispanic, 19% black, 18% white) were assessed for total plaque area (TPA) burden using 2-dimensional carotid ultrasound imaging. Multiple linear regression models were constructed. Model 1 used prespecified traditional risk factors: age, sex, low-density lipoprotein cholesterol, diabetes mellitus, pack-years of smoking, blood pressure, and treatment for blood pressure; and Model 2, an addition of socioeconomic and less traditional risk factors. The contributions of the components of the Framingham heart risk score and the NOMAS Global Vascular Risk Score to the TPA were explored. Results— Prevalence of carotid plaque was 58%. Mean TPA was 13±19 mm2. Model 1 explained 19.5% of the variance in TPA burden (R2=0.195). Model 2 explained 21.9% of TPA burden. Similarly, the Framingham heart risk score explained 18.8% and NOMAS global vascular risk score 21.5% of the TPA variance. Conclusions— The variation in preclinical carotid plaque burden is largely unexplained by traditional and less traditional vascular risk factors, suggesting that other unaccounted environmental and genetic factors play an important role in the determination of atherosclerotic plaque. Identification of these factors may lead to new approaches to prevent stroke and cardiovascular disease.

Insomnia characteristics and clinical correlates in Operation Enduring Freedom/Operation Iraqi Freedom veterans with post-traumatic stress disorder and mild traumatic brain injury: An exploratory study

BACKGROUND There is limited data on chronic insomnia in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans, in whom post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) often co-exist. Our aim was to compare sleep characteristics of three groups of OEF/OIF veterans: (1) healthy sleepers (HS), (2) those with insomnia associated with PTSD and mTBI (PTSD-mTBI), and (3) those with insomnia associated with PTSD alone. METHODS Consecutive veterans with insomnia complaints (> 6 months) were recruited over 6 months from the Miami VA Post Deployment clinic. Participants completed a sleep disorders clinical interview, medical history, and questionnaires about insomnia, sleepiness, pain, fatigue, depression, PTSD, and health-related quality of life. They underwent polysomnography (PSG) with 2 weeks of actigraphy (ACT) and sleep diaries. RESULTS There were no differences in demographics or most questionnaire responses between PTSD and PTSD-mTBI groups. Subjective daytime sleepiness was significantly greater in PTSD-mTBI subjects compared with HS and PTSD participants. Significant co-morbid sleep disorders were noted in insomnia patients. PSG and ACT wake after sleep onset was significantly shorter in PTSD-mTBI subjects as compared with PTSD participants. CONCLUSION Insomnia patients with PTSD-mTBI were subjectively sleepier despite spending less time awake during the night than PTSD subjects, possibly as a consequence of head trauma.

Adiponectin and Carotid Intima-Media Thickness in the Northern Manhattan Study

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 multiethnic cohort study of stroke risk factors. Methods— 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. Results— The mean adiponectin level was 10.3±5.2 &mgr;g/mL (median, 9.2 &mgr;g/mL; range, 2.3–53.3 &mgr;g/mL), 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. Conclusions— Our findings suggest that low adiponectin is associated with increased IMT in a multiethnic cohort and support a protective role for adiponectin in atherosclerosis.

Heritability and Linkage Analysis for Carotid Intima-Media Thickness The Family Study of Stroke Risk and Carotid Atherosclerosis

Background and Purpose— The aim of this study was to identify quantitative trait loci (QTL) for carotid intima-media thickness (CIMT) a risk factor for stroke and cardiovascular disease. Methods— Probands were selected from Caribbean Hispanic subjects of the population-based Northern Manhattan Study. CIMT was measured by high-resolution B-mode ultrasound and expressed as the mean (IMTx) and mean of the maximum (IMTm). Variance components methodology was used to detect linkage using SOLAR and calculate locus-specific heritability. Ordered-subset Analysis was done based on history of hypertension and total cholesterol levels. Results— Among 100 Dominican families, 1390 subjects had CIMT measured (848 females; mean age 46.2 years). CIMT had a heritability of 0.65 after adjusting for age, age2, sex, cigarette pack-years, waist hip ratio, and BMI. Adjusted maximum multipoint LOD scores >2 were found on chromosomes 14q (D14S606) and 7p (D7S817). Linkage to chromosome 14q was significantly increased in a subset of families with the greatest history of hypertension (MLOD=4.12). The QTL on Ch14q accounted for 0.21 of the heritability of IMTm, and on Ch7p 0.27 of the heritability of BIFm. Conclusions— Several QTLs for CIMT were found on chromosomes 7p and 14q. The QTL on 14q replicates a suggestive linkage peak delimited in the Framingham Heart Study. These QTLs accounted for a substantial amount of trait heritability and warrant further fine mapping.

Lipids and carotid plaque in the Northern Manhattan Study (NOMAS)

BackgroundLipids, particularly low-density (LDL) and high-density (HDL) lipoproteins, are associated with increased risk of stroke and cardiovascular disease, probably due to atherosclerosis. The objective of this cross-sectional analysis was to investigate the relation between blood lipids and carotid plaque.MethodsAs part of a prospective population-based study to determine the incidence and risk factors of stroke in a multiethnic population, we evaluated 1804 participants with lipid measurements and B-mode ultrasound of carotid arteries (mean age 69 +/- 10 years; 40% men; 51% Hispanic, 26% black, 23% white). The association between lipid parameters and carotid plaque was analyzed by multiple logistic regression.ResultsPlaque was present in 61% of participants. Mean total cholesterol was 202 +/- 41 mg/dl. After controlling for other lipid parameters, demographics, and risk factors, the only cholesterol subfraction associated with carotid plaque was LDL (OR per standard deviation (SD) = 1.14, 95% CI 1.02-1.27). Neither HDL nor triglycerides independently predicted carotid plaque. Apolipoprotein B (ApoB) was also associated with risk of plaque (OR per SD = 1.29, 95% CI 1.03-1.60). Apolipoprotein A-I (apoA-1) was associated with a decrease in multiple plaques (OR per SD = 0.76, 95% CI 0.60-0.97), while lipoprotein a was associated with an increased risk of multiple plaques (OR per SD = 1.31, 95% CI 1.03-1.66). ApoB:ApoA-I had the strongest relation with carotid plaque (OR per SD = 1.35, 95% CI 1.08-1.69).ConclusionsAmong the common lipid parameters, LDL has the strongest relation with carotid plaque. Other lipid precursor proteins such as ApoB and ApoA-I may be stronger predictors of subclinical atherosclerosis, however, and better targets for treatment to reduce plaque formation and risk of cerebrovascular disease.