Familial transmission of stroke and myocardial infarction (MI) is partially mediated by transmission of cerebrovascular and cardiovascular risk factors. We examined relationships between family risk of stroke and MI with risk factors for these phenotypes.
Cross-sectional association between the stratified log-rank family score (SLFS) for stroke and MI with prevalent risk factors was assessed in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Individuals in the 4th quartile of SLFS scores for stroke were more likely to have prevalent risk factors including hypertension (OR: 1.43; 95% CI: [1.30, 1.58]), left ventricular hypertrophy (OR 1.42; 95% CI: [1.16, 1.42]), diabetes (OR: 1.26; 95% CI: [1.12, 1.43]) and atrial fibrillation (OR 1.23; 95% CI: [1.03, 1.45]) compared to individuals in the 1st quartile. Likewise, individuals in the 4th quartile of SLFS scores for MI were more likely to have prevalent risk factors including hypertension (OR 1.57; 95% CI: [1.27, 1.94]) and diabetes (OR 1.29; 95% CI: [1.12, 1.43]) than the 1st quartile. In contrast to stroke, the family risk score for MI was associated with dyslipidemia (OR 1.38; 95% CI: [1.23, 1.55]) and overweight/obesity (OR 1.22; 95% CI: [1.10, 1.37]).
Family risk of stroke and MI are strongly associated with the majority of risk factors associated with each disease. Family history and genetic studies separating nonspecific contributions of intermediate phenotypes from specific contributions to the disease phenotype may lead to more thorough understanding of transmission for these complex disorders.
stroke; myocardial infarction; cohort studies; family risk; REGARDS
Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms.
RESEARCH DESIGN AND METHODS
This study included 25,696 individuals aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003–2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire.
The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18–1.39]) and two or more stroke symptoms (1.26 [1.12–1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03–1.29]), vision loss (1.52 [1.31–1.76]), half-vision loss (1.54 [1.30–1.84]), and lost ability to understand people (1.34 [1.12–1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms.
In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.
Background and Purpose
Diabetes and hypertension impart approximately the same increased relative risk for stroke, although hypertension has a larger population-attributable risk because of its higher population prevalence. With a growing epidemic of obesity and associated increasing prevalence of diabetes that disproportionately impacts the southeastern Stroke Belt states, any potential contribution of diabetes to the geographic disparity in stroke mortality will only increase.
Racial and geographic differences in diabetes prevalence and diabetes awareness, treatment, and control were assessed in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants older than 45 years of age. At the time of this report, 21 959 had been enrolled.
The odds of diabetes were significantly increased in both white and black residents of the stroke buckle (OR, 1.26; [1.10, 1.44]; OR, 1.45 [1.26, 1.66], respectively) and Stroke Belt (OR, 1.22; [1.09, 1.36]; OR, 1.13 [1.02, 1.26]) compared to the rest of the United States. In the buckle, regional differences were not fully mediated and remained significant when controlling for socioeconomic status and risk factors. Addition of hypertension to the models did not reduce the magnitude of the associations. There were no significant differences by region with regard to awareness, treatment, or control for either race.
These analyses support a possible role of regional variation in the prevalence of diabetes as, in part, an explanation for the regional variation in stroke mortality but fail to support the potential for a contribution of regional differences in diabetes management.
diabetes; geography; racial differences
High waist circumference (WC) (women: >88 cm; men: >102 cm) increases cardiovascular risk. Less is known about moderate WC (women: 80–88 cm; men: 94–102 cm). Therefore, we examined the association between moderate WC and hypertension prevalence, independent of body mass index (BMI).
Among 24,247 eligible adults 45–84 years old, when recruited from January 2003 to October 2007 in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we examined hypertension prevalence (systolic blood pressure (BP) ≥140 mm Hg, or diastolic BP ≥90 mm Hg, or self-reported antihypertensive medication use) by WC before and after stratification by BMI (normal: 18.5–24.9; overweight: 25–29.9; obese class I: 30–34.9). Logistic regression adjusted associations between WC, BMI, and hypertension prevalence for age, race, sex, region, income, education, cigarette smoking, glomerular filtration rate, alcohol use, and physical activity.
Overall, hypertension prevalence was 44% among those with low WC (n = 8,068), 55% with moderate WC (n = 6,488), and 66% with high WC (n = 9,691). After full adjustment, moderate WC was independently associated with hypertension prevalence among persons with normal BMI, (adjusted odds ratio (aOR), 1.49; 95% confidence interval (CI), 1.31–1.70), overweight BMI (aOR, 1.80; 95% CI, 1.64–1.98), and obese class I BMI (aOR, 2.28; 95%CI, 1.96–2.65) (referent: low WC-normal BMI). The moderate WC–hypertension association was observed in blacks and whites and in men and women.
Moderate WC is associated with hypertension prevalence independent of BMI and several hypertension risk factors in middle-aged and older adults.
blood pressure; clinical epidemiology; hypertension; obesity; race; waist circumference
The Minnesota Code (MC) and Novacode (Nova) are the most widely used electrocardiographic (ECG) classification systems. The comparative strengths of their classifications for Q- and ST-T–wave abnormalities in predicting coronary heart disease (CHD) events and total mortality have not been evaluated separately by gender. We studied standard 12-lead electrocardiograms at rest from 4,988 participants in the Cardiovascular Health Study. Average age at baseline was 73 years, 60% of participants were women 85% were white, and 22% had a history of cardiovascular disease or presence of ECG myocardial infarction by MC or Nova. Starting in 1989 with an average 17-year follow-up, 65% of participants died and 33% had incident CHD in a cohort free of cardiovascular disease at baseline. Of these, electrocardiograms with major Q-wave or major ST-T abnormalities by MC or Nova predicted increased risk for CHD events and total mortality with no significant differences in predictability between men and women. The study also found that women had fewer major Q-wave changes but more major ST-T abnormalities than men. However, there were no gender differences in predicting CHD events and total mortality. In conclusion, ECG classification systems for myocardial infarction/ischemia abnormalities by MC or Nova are valuable and useful for men and women in clinical trials and epidemiologic studies.
A US national sample of 20,962 participants (57% women, 44% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study provided general population estimates for ECG abnormalities among black and white men and women. Participants were recruited during 2003–2007 by random selection from a commercially available nationwide list, with oversampling of blacks and persons from the stroke belt for a cooperation rate of 49%. Measurement of risk factors and 12-lead ECGs (centrally coded using Minnesota Code criteria) showed 28% had at least one major ECG abnormality. Prevalence of abnormalities was higher (35%+) for those 65 years and older with no differences between blacks and whites. However, among men less than 65 years, blacks had more major abnormalities than whites, most notably for atrial fibrillation, major Q waves and left ventricular hypertrophy (LVH). Men generally had more ECG abnormalities than women. The most common ECG abnormalities were T-wave abnormalities. Average heart rate corrected QT interval was longer in women than men, similar in whites and blacks and increased with age, whereas the average heart rate was higher in women than men and in blacks than whites and decreased with age. The prevalence of ECG abnormalities was related to hypertension, diabetes, blood pressure level and age. In conclusion, black men and women in the US have a significantly higher prevalence of ECG abnormalities than whites at ages 45–64 but these proportions, although larger, tend to equalize or reverse after age 65.
ECG abnormalities; prevalence; black/white
Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy (LVH) is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial (MRFIT), which randomly assigned 8,012 hypertensive men to special intervention (SI) or usual care (UC). SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic used (C-clinics: CTD; H-clinics: HCTZ). After 48 months, SI participants receiving HCTZ were recommended to switch to CTD, in part, because higher mortality was observed for SI compared to UC participants in H-clinics, while the opposite was found in C-clinics. In this analysis, we examined change in continuous measures of electrocardiographic LVH using both an ecologic analysis by previously-reported C- or H-clinic groupings, and an individual participant analysis where use of CTD or HCTZ by SI participants was considered and updated annually. Through 48 months, differences between SI and UC in LVH were larger for C-clinics compared to H-clinics (Sokolow-Lyon: −93.9 vs −54.9 μV, P=0.049; Cornell voltage: −68.1 vs −35.9 μV, P=0.019; Cornell voltage product: −4.6 vs −2.2 μV/ms, P=0.071; left ventricular mass: −4.4 vs −2.8 gm, P=0.002). At the individual participant level, Sokolow-Lyon and left ventricular mass were significantly lower for SI men receiving CTD compared to HCTZ through 48 months and 84 months of follow-up. Our findings on LVH support the idea that greater blood pressure reduction with CTD than HCTZ may have led to differences in mortality observed in MRFIT.
hydrochlorothiazide; chlorthalidone; left ventricular hypertrophy; hypertension; blood pressure; electrocardiography
It remains debated whether to include resting electrocardiogram (ECG) in the routine care of patients infected with Human immunodeficiency virus (HIV). This is largely because data are limited regarding the prevalence and prognostic significance of ECG abnormalities in HIV-infected patients.
This analysis included 4518 HIV-infected patients (28% females and 29% blacks) from The Strategies for Management of Antiretroviral Therapy (SMART) study, a clinical trial aimed to compare two HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Multivariable adjusted Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease.
More than half of the participants (N=2325, 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 (3.4%) participants developed incident cardiovascular disease. After adjusting for the study treatment arms, the presence of major, minor, and either minor or major ECG abnormalities were significantly predictive of incident cardiovascular disease [Hazard ratio (95% Confidence Interval): 2.76 (1.74, 4.39), p<0.001; 1.58 (1.14, 2.20), p=0.006; 1.57 (1.14, 2.18), p=0.006, respectively]. However, after adjusting for demographics, common cardiovascular risk factors and HIV characteristics (full model), presence of major ECG abnormalities was still significantly predictive of cardiovascular disease [1.83 (1.12, 2.97), p=0.015)], but not minor or minor or major abnormalities taken together [1.26 (0.89, 1.79), p=0.18; 1.25 (0.89, 1.76), p=0.20, respectively]. Individual ECG abnormalities that significantly predicted cardiovascular disease in the fully adjusted model included major isolated ST/T abnormalities, major prolongation of QT interval, minor isolated ST/T and minor isolated Q/QS abnormalities.
Nearly one in two of the HIV-infected patients in SMART study had ECG abnormalities; one in thirteen had major ECG abnormalities. Presence of ECG abnormalities, especially major ECG abnormalities was independently predictive of incident cardiovascular disease. These results suggest that the ECG could provide a convenient risk screening tool in HIV-infected patients.
HIV/AIDS; ECG; Cardiovascular Disease; SMART Study
Death certificates may lack accuracy and misclassify the cause of death. The validity of proxy-reported cause of death is not well established. The authors examined death records on 336 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a national cohort study of 30,239 community-dwelling US adults (2003–2010). Trained experts used study data, medical records, death certificates, and proxy reports to adjudicate causes of death. The authors computed agreement on cause of death from the death certificate, proxy, and adjudication, as well as sensitivity and specificity for certain diseases. Adjudicated cause of death had a higher rate of agreement with proxy reports (73%; Cohen's kappa (κ) statistic = 0.69) than with death certificates (61%; κ = 0.54). The agreement between proxy reports and adjudicators was better than agreement with death certificates for all disease-specific causes of death. Using the adjudicator assessments as the “gold standard,” for disease-specific causes of death, proxy reports had similar or higher specificity and higher sensitivity (sensitivity = 50%–89%) than death certificates (sensitivity = 31%–81%). Proxy reports may be more concordant with adjudicated causes of death than with the causes of death listed on death certificates. In many settings, proxy reports may represent a better strategy for determining cause of death than reliance on death certificates.
cause of death; death certificates; epidemiologic methods; prospective studies; proxy
Atherosclerosis is a risk factor for dementia. Yet little is known about the association between cognitive performance and a widely used indicator of coronary heart disease, the resting electrocardiogram (ECG). We identified 839 older residents (mean age 81; 58% black) from a geographically defined biracial community in Chicago, Illinois, who underwent extensive cognitive performance testing and met ECG eligibility criteria, including a QRS duration less than 120 msec. We then examined multivariable regression coefficients that describe associations between global cognitive performance and 4 novel descriptors of ventricular repolarization waveforms. All analyses were adjusted for age, sex, education, and race. T wave non-dipolar voltage had a significant association with global cognitive performance (p = 0.01), and this association largely remained after adjustment for cardiovascular disease risk factors (p = 0.03). In contrast, global cognitive performance was not significantly associated with the rate-adjusted QT interval, the voltage change from beginning to end of the ST segment in lead V5, or the spatial angle between mean QRS and T wave vectors. In conclusion, strengths of associations varied between novel ECG descriptors of ventricular repolarization and global cognitive performance. Nevertheless, the significant association observed with T wave non-dipolar voltage suggests that the cardiac effects of heart disease are associated with cognitive decline.
cognitive performance; ventricular repolarization; T wave non-dipolar voltage
Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial.
SNA definitions were developed based upon the following: (1) criteria from a previous trial (SMART), (2) review of published literature, (3) an iterative consultation and review process with the ERC and other content experts, and (4) evaluation of draft SNA criteria using retrospectively collected reports in another trial (ESPRIT).
Final criteria are presented for acute myocardial infarction, congestive heart failure, coronary artery disease requiring drug treatment, coronary revascularization, decompensated liver disease, deep vein thrombosis, diabetes mellitus, end-stage renal disease, non-AIDS cancer, peripheral arterial disease, pulmonary embolism, and stroke. Of 563 potential SNA events reported in ESPRIT and reviewed by an ERC, 72% met “confirmed” and 13% “probable” criteria. Twenty-eight percent of cases initially reviewed by the ERC required follow-up discussion (adjudication) before a final decision was reached.
HIV clinical trials that include SNA diseases as clinical outcomes should have standardized SNA definitions to optimize event reporting and validation and should have review by an experienced ERC with opportunities for adjudication.
clinical trials; cardiovascular disease; endpoint review committees; HIV; serious non-AIDS events
The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease (ESRD), with limited data on less advanced chronic kidney disease (CKD) stages.
A total of 3267 adult participants (50% non-Hispanic blacks, 46% females) with CKD from the Chronic Renal Insufficiency Cohort (CRIC) were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (N=323) or those without ECG data (N=22) were excluded. AF was ascertained by a 12-lead electrocardiogram (ECG) and self-report. Age- sex- race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable adjusted logistic regression analysis.
The mean estimated glomerular filtration rate (GFR) was 43.6 (±13.0) ml/min/1.73 m2. AF was present in 18% of the study population and in more than 25% of those 70 years or older. In multivariable adjusted models, 1-SD increase in age (11 years) [odds ratio (OR) and CI 95%: 1.27 (1.13, 1.43), P<0.0001], female sex [0.80 (0.65, 0.98), P=0.0303], smoking (former vs. never) [1.34 (1.08, 1.66), P= 0.0081], history of heart failure [3.28 (2.47, 4.36), P<0.001], and history of cardiovascular disease [1.94 (1.56, 2.43), P<0.0001] were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated GFR <45 ml/min/1.73 m2 was associated with AF in an unadjusted model [1.35 (1.13–1.62)); P=0.0010)], but not after multivariable adjustment [1.12 (0.92– 1.35), P=0.2710].
Nearly one in five participants in CRIC, a national study of CKD, had evidence for AF at study entry, a prevalence similar to that reported among patients with ESRD and 2–3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.
To minimize participants’ burden and the need for disrobing, a 7-lead electrocardiogram (ECG) recording using a single mid-sternal chest lead was recorded at the initial stages of The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. ECG-detected left ventricular hypertrophy (ECG-LVH) by Cornell voltage (RaVL +SV3) cannot be assessed from this method because of the absence of V3. We examined the possibility that the S wave amplitude in the mid-sternal lead (SV) could be used as a surrogate for SV3.
The REGARDS study is a US national study where 7-lead ECGs were performed in 8,330 (29%) participants and standard 12-lead EGCs were performed in 20,811 (71%). Cornell voltage was calculated as the sum of aVL amplitude + SV (in the 7-lead group) or SV3 (in the 12-lead group). Logistic regression analysis was used to examine and compare the magnitude of the association between the LVH risk factors with ECG-LVH in both groups, and Cox Proportional Hazards analysis was used to examine and compare the hazard ratios of overall mortality and cardiovascular mortality associated with ECG-LVH in both groups.
Regardless of the Cornell voltage calculation method, ECG-LVH was significantly associated with LVH risk factors, and with the exception of sex there was no evidence of a difference in the magnitude of the association. ECG-LVH from both approaches were significantly and similarly associated with both all cause and cardiovascular mortality.
ECG-LVH by Cornell voltage calculated from a 7-lead ECG (using SV in the formula) has demographic and clinical associations that are similar to that calculated from a standard 12-lead ECG (using SV3). In epidemiologic studies recording 7-lead ECG, SV could be used as an alternative to SV3 in the Cornell voltage formula.
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for LV mass measurement. Ethnicity is believed to affect ECG performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity.
Methods and Results
Data were analyzed from 4967 participants (48% males, mean age 62 ± 10 years; 39% Caucasian, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 yearsfor incident CVD. Thirteen traditional ECG-LVH criteria were assessed and showed overall and ethnicity-specific low sensitivity (10–26%) and high specificity (88–99%) in diagnosing MRI-defined LVH. 10 out of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared to Caucasians (p=0.02–0.001). The sum of amplitudes of S wave in V1, S wave in V2 and R wave in V5 (a MESA specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared to prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (ROC area=0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product and Framingham-adjusted Cornell voltage predicted increased CVD risk (p<0.05).
ECG has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared to other ethnic groups.
Studies suggest that diabetes may specifically elevate risk of sudden cardiac death in excess of other heart disease outcomes. In this study, we examined the association of type 2 diabetes with incidence of sudden cardiac death as compared to the incidence of non-sudden cardiac death and non-fatal myocardial infarction (MI). We used data from the Atherosclerosis Risk in Communities (ARIC) study to examine incidence of sudden and non-sudden cardiac death and non-fatal MI among persons with and without diabetes in follow-up from the baseline data collection (1987-1989) through December 31, 2001. There were 209 cases of sudden cardiac death, 119 of non-sudden cardiac death, and 739 of non-fatal MI identified in this cohort over an average 12.4 years of follow-up. In analyses adjusted for age, race/ARIC center, gender, and smoking, the Cox proportional hazard ratio of the association of baseline diabetes was 3.77 (95% CI 2.82, 5.05) for sudden cardiac death, 3.78 (95% CI 2.57, 5.53) for non-sudden cardiac death, and 3.20 (95% CI 2.71, 3.78) for non-fatal MI. Elevated risk for each of the three outcomes associated with diabetes was independent of adjustment for measures of blood pressure, lipids, inflammation, hemostasis, and renal function. Among those with diabetes, the risk of cardiac death, but not of non-fatal MI, was similar for men and women. Findings from this prospective, population-based cohort investigation indicate that diabetes does not confer a specific excess risk of sudden cardiac death. Our results suggest that diabetes attenuates gender-differences in risk of fatal cardiac events.
sudden cardiac death; myocardial infarction; cohort study; diabetes; coronary heart disease
Experimental and clinical trial data suggest an association between fish oil intake and atrial fibrillation (AF). However, prior observational studies have reported conflicting results regarding this association. Thus, we sought to compare the association between dietary fish intake and incident AF in a large sample of older, postmenopausal women. We included 44,720 participants from the Women's Health Initiative clinical trials not enrolled in the dietary modification intervention arm and without AF at baseline. The dietary intake of non-fried fish and omega-3 fatty acid intake were estimated from a Food Frequency Questionnaire at study entry. Incident AF was determined by follow-up ECG at year 3 and year 6. Baseline characteristics and rates of incident AF were compared across quartiles (Q) of fish intake. Adjusted logistic regression models were used to evaluate the association between dietary non-fried fish intake and incident AF. There were 378 incident cases of AF in follow-up. In age-adjusted models, there was no association between dietary non-fried fish intake and incident AF [odds ratios (95% confidence intervals) 1.17 (0.88–1.57) for Q 4 vs. Q 1 of dietary fish intake). Similar findings were observed in multivariable models and in subgroup analyses. In a large cohort of healthy women, we found no evidence of an association between fish or omega-3 fatty acid intake and incident AF.
atrial fibrillation; diet; omega-3 fatty acids
This study examines the hypothesis that chronic inflammation is associated with a higher risk of cardiac death compared to the risk of non-fatal myocardial infarction.
Cardiac death and non-fatal MI events were identified in the ARIC cohort during follow-up from 1987 through 2001. Markers of inflammation and hemostasis were determined at baseline using standardized procedures. Cox proportional hazard regression and polytomous logistic regression were used to estimate associations.
We observed a positive gradient in incidence of sudden cardiac death, non-sudden cardiac death and non-fatal MI in association with decreasing levels of albumin and increasing levels of white blood cell count and of markers of hemostasis (fibrinogen, von Willebrand factor, factor VIIIc). Associations for von Willebrand factor (vWF) and factor VIIIc were stronger for fatal relative to non-fatal events (3rd versus 1st tertile hazard ratios: vWF: SCD 2.67 (95% CI 1.80, 3.96), NSCD 2.11 (95% CI 1.40, 3.19), non-fatal MI 1.40 (95% CI 1.17, 1.67); factor VIIIc: SCD 2.58 (95% CI 1.77, 3.78), NSCD 2.01 (95% CI 1.38, 2.93), non-fatal MI 1.48 (95% CI 1.24, 1.78). Gradients of association for fibrinogen and white blood cell count, examined over tertiles of distribution and per one SD increase, were similar for the three endpoints. All associations were independent of smoking status.
Von Willebrand factor and factor VIIIc are associated with an increased risk of cardiac death as compared to the risk of non-fatal MI.
hemostasis; inflammation; von Willebrand factor; sudden cardiac death; non-fatal myocardial infarction
Among persons treated for hypertension, Blacks are more likely to have uncontrolled blood pressure compared to Whites. Few studies have focused on trust in physicians as a potential contributor to this disparity in blood pressure (BP) control. The primary objective of this study was to assess the relationship between trust in physicians and blood pressure control among Blacks and Whites being treated for hypertension.
Cross-sectional analysis of baseline data collected from the REasons for Geographic And Racial Differences in Stroke cohort, a US national, population-based cohort study. Participants were recruited by telephone from 2003–2007, completed a telephone survey, and had BP measured during an in-home visit.
2843 Black and White adults aged >45 years with treated hypertension.
Main Outcome Measures
Uncontrolled blood pressure was defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg. For participants with diabetes, renal disease, or self-reported previous myocardial infarction, uncontrolled blood pressure was defined as systolic blood pressure >130 mm Hg or diastolic blood pressure >80 mm Hg.
Trust in physicians was not associated with uncontrolled blood pressure in either unadjusted (odd ratio [OR] 1.07; 95% confidence interval [CI] 0.92, 1.25) or adjusted analyses (OR 0.97; 0.83, 1.14). Both Black race (OR 1.58; 1.36, 1.84) and imperfect medication adherence (OR 1.56; 1.31, 1.86) were associated with higher odds of uncontrolled blood pressure.
Trust in physicians was not related to blood pressure control among Blacks and Whites with treated hypertension in this sample. The racial disparity in blood pressure control was not completely explained by trust in physicians or medication adherence, and a better understanding of the mechanisms leading to this disparity is needed.
Hypertension; Trust; Disparities
Evidence is mounting regarding the clinically significant effect of temperature on blood pressure.
In this cross-sectional study the authors obtained minimum and maximum temperatures and their respective previous week variances at the geographic locations of the self-reported residences of 26,018 participants from a national cohort of blacks and whites, aged 45+. Linear regression of data from 20,623 participants was used in final multivariable models to determine if these temperature measures were associated with levels of systolic or diastolic blood pressure, and whether these relations were modified by stroke-risk region, race, education, income, sex hypertensive medication status, or age.
After adjustment for confounders, same-day maximum temperatures 20°F lower had significant associations with 1.4 mmHg (95% CI: 1.0, 1.9) higher systolic and 0.5 mmHg (95% CI: 0.3, 0.8) higher diastolic blood pressures. Same-day minimum temperatures 20°F lower had a significant association with 0.7 mmHg (95% CI: 0.3, 1.0) higher systolic blood pressures but no significant association with diastolic blood pressure differences. Maximum and minimum previous-week temperature variabilities showed significant but weak relationships with blood pressures. Parameter estimates showed effect modification of negligible magnitude.
This study found significant associations between outdoor temperature and blood pressure levels, which remained after adjustment for various confounders including season. This relationship showed negligible effect modification.
The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 × 10−8. Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.
Isolated minor non-specific ST-segment and T-wave (NSSTA), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study is to define the association between ECG abnormalities and measures of subclinical atherosclerosis. We studied participants from MESA, a multi-ethnic sample of men and women aged 45–84 and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, resting 12-lead electrocardiograms, coronary artery calcium (CAC) measurement and common carotid intima-media thickness (CCIMT). Electrocardiograms were coded using Novacode criteria and were defined as having either minor abnormalities (e.g., minor non-specific STTA, first degree atrioventricular block, and QRS axis deviations) or major abnormalities (e.g., pathologic Q waves, major ST-segment and T-wave abnormalities, significant dysrhythmias and conduction system delays). Multivariable logistic and linear regressions were used to determine the cross-sectional associations of ECG abnormalities with CAC and common carotid-IMT. Among 6710 participants, 52.7% were women, with a mean age of 62 years. After multivariable-adjustment, isolated minor STTA, minor and major ECG abnormalities were not associated with the presence of CAC (>0) among men (OR 1.04, 95% CI 0.81–1.33; 1.10, 0.91–1.32; and 1.03, 0.81–1.31, respectively) or women (1.01, 0.82–1.24; 1.04, 0.87–1.23; and 0.94, 0.73–1.22, respectively). Lack of association remained consistent when using both log CAC and CC-IMT as continuous variables. ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multi-ethnic cohort.
Adult obesity and hypertension are leading causes of cardiovascular morbidity/mortality. Although childhood body mass index and blood pressure track into adulthood, how they influence adult cardiovascular risk independent of each other is not well defined.
Participants were from two longitudinal studies with a baseline evaluation at mean age 13 and a follow-up at mean age 24. Regression models using childhood blood pressure and body mass index to predict young adult cardiovascular risk factors were performed.
In univariate analysis, childhood body mass index predicted young adult blood pressure, lipids, glucose, insulin, and insulin resistance, while childhood blood pressure predicted young adult blood pressure, lipids and glucose. In a multivariable regression model (adjusted for age, sex and race) which included change in body mass index and blood pressure from age 13 to 24, body mass index predicted all young adult risk factors except blood pressure and glucose. Baseline systolic blood pressure predicted young adult blood pressure, cholesterol, triglycerides and glucose while baseline diastolic blood pressure predicted young adult blood pressure, body mass index and glucose.
The results from this study show that 1) blood pressure and body mass index act independently in children to influence future cardiovascular risk factors, and 2) the combination of high blood pressure and body mass index in childhood have an additive effect in predicting the highest levels of young adult cardiovascular risk. Thus, there should be a focus on treating hypertension in overweight and obese children, in addition to attempting to reduce weight.
adolescents; young adults; risk factors; blood pressure; body mass index
Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality.
Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates.
There was no relationship between CHD and stroke mortality rates (r = 0.04; p = 0.78), but there was between CHD and stroke risk scores at the individual (r = 0.68; p < 0.0001) and state (r = 0.64, p < 0.0001) level. There was a stronger (p < 0.0001) association between state-level FCRS and state-level CHD mortality (r = 0.28, p = 0.18), than between FSRS and stroke mortality (r = 0.12, p = 0.56).
Weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest geographic variation in risk factors may not underlie geographic variations in stroke and CHD mortality. The relationship between risk factor scores and mortality was stronger for CHD than stroke.
Stroke; Coronary Heart Disease; Geography; Risk Factors; Mortality
To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African-Americans.
African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African-Americans have not been previously published.
We studied the incidence of AF in the Atherosclerosis Risk in Communities Study, which has followed up 15,792 men and women aged 45-65 at baseline from four communities in the United States since 1987. AF cases were identified from ECGs conducted at baseline and three follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African-Americans, 889 in whites).
Crude incidence rates of AF were 6.7, 4.0, 3.9 and 3.0 per 1,000 persons per year in white men, white women, African-American men and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% confidence interval: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at age 80 was 21% in white men, 17% in white women, and 11% in African-American men and women.
In this population-based cohort, African-Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before the age of 80.
atrial fibrillation; epidemiology; incidence; African-Americans; lifetime risk
Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA.
We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002–07, population ∼1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (p<5×10−8). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10−4 and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01).
A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study.