Editorials; atrial fibrillation
It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.
In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15439 participants (baseline 45–64 years, 55% women, and 27% black) from baseline (1987–1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline ≥65 years, 58% women, and 15% black) from baseline (first cohort, 1989–1990; second cohort, 1992–1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD): coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.
In ARIC, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89/1000 person-years (with AF) and 1.30/1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CI) of AF for SCD and NSCD were 3.26 (2.17–4.91) and 2.43 (1.60–3.71), respectively. In CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00/1000 person-years (with AF) and 3.82/1000 person-years (without AF). The multivariable HRs (95% CI) of AF for SCD and NSCD were 2.14 (1.60–2.87) and 3.10 (2.58–3.72), respectively. The meta-analyzed HRs (95% CI) of AF for SCD and NSCD were 2.47 (1.95–3.13) and 2.98 (2.52–3.53), respectively.
Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in AF patients is warranted.
Widening of the electrocardiographic [ECG] spatial QRS-T angle has been predictive of cardiovascular disease [CVD] events in the general population. However, its prognostic significance in HIV-infected individuals remains unknown. Spatial QRS-T angle was derived from the baseline ECG of 4453 HIV-infected patients aged 43.5 (SD 9.3) years from the Strategies for Management of Antiretroviral Therapy [SMART] trial. CVD events were identified during a median follow up of 28.7 months. Quartiles of spatial QRS-T angle was calculated for males and females separately, and values in the upper quartile were considered as widened angle (values above 74° for women and 93° for men). Multivariable Cox proportional hazards analysis was used to examine the association between widened baseline spatial QRS-T angle and incident CVD events. During 11965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events per 100 person-years. The rate of CVD events in individuals with widened spatial QRS-T angle was almost double the rate in those with normal spatial QRS-T angle [Rate ratio (95% CI) of 1.94 (1.40, 2.69); p <0.001]. In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers and other ECG abnormalities, widened spatial QRS-T angle was associated with more than 50% increased risk of CVD events compared to normal spatial QRS-T angle [Hazard ratio (95% CI): 1.53 (1.07, 2.17); p= 0.02]. There was no interaction by SMART trial arms [p-value for interaction 0.37] or by gender [p-value for interaction 0.84]. In Conclusion, widened spatial QRS-T angle is independently predictive of CVD events in HIV-infected patients on antiretroviral therapy. This highlights the potential role of routine ECG as a simple non-invasive CVD risk-screening tool in HIV-infected individuals.
Spatial QRS-T angle; Electrocardiogram; HIV/AIDS
Autonomic fluctuations are associated with the initiation and possibly maintenance of atrial fibrillation (AF). However, little is known about the relationship between orthostatic blood pressure change, a common manifestation of autonomic dysfunction, and incident AF.
We examined whether supine-to-standing changes in systolic blood pressure (SBP) are associated with incident AF in 12,071 African American and white men and women aged 45–64 years, enrolled in the Atherosclerosis Risks in Communities (ARIC) study. Orthostatic hypotension (OH) was defined as a supine-standing drop in SBP by ≥20 mmHg or diastolic blood pressure by ≥10 mmHg. AF cases were identified based on study scheduled 12-lead ECG, hospital discharge ICD codes, and death certificates through 2009.
OH was seen in 603 (5%) at baseline. During an average follow-up of 18.1 years, 1438 (11.9%) study participants developed AF. Incident AF occurred more commonly among those with OH than those without, a rate of 9.3 vs. 6.3 per 1000 person years, (p<0.001). The age, gender, and race adjusted hazard ratio (95%CI) of AF among those with OH compared to those without was 1.62 (1.34, 2.14). This association was attenuated after adjustment for common AF risk factors to HR 1.40 (1.15, 1.71), a strength similar to that of diabetes or hypertension with AF in the same model. A non-linear relationship between orthostatic change in SBP and incident AF was present after multivariable adjustment.
OH is associated with higher AF incidence. Whether interventions that decrease OH can reduce AF risk remains unknown.
Prolonged QRS duration (QRSd) on the electrocardiogram (ECG) has been associated with cardiac structural and functional abnormalities by echocardiography and an increased risk of heart failure (HF). Data are sparse on these relationships in middle-aged and elderly individuals free of baseline cardiovascular disease with respect to cardiac magnetic resonance imaging (MRI). We sought to determine whether QRSd is associated with incident HF and measures of cardiac structure and function by cardiac MRI.
Methods and results
We analysed baseline ECGs in the Multi-Ethnic Study of Atherosclerosis (MESA) to determine whether QRSd >100 ms was associated with incident HF. We adjusted for demographic and clinical risk factors, as well as MRI measures of left ventricular (LV) structure and function. Among 4591 eligible participants (51% women; 39% white; mean age 61 years), 75 developed incident HF over a mean follow-up of 7.1 years. QRSd >100 ms was significantly associated with MRI measures of cardiac structure and function, as well as incident HF, even after adjustment for demographic covariates [hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.29–3.42; P = 0.003] and clinical risk factors (HR 1.86, 95% CI 1.14–3.03; P = 0.01). With further adjustment for individual LV structural measures, findings were attenuated to non-significance. Separate adjustment for LV functional measures yielded only mild attenuation.
In middle-aged and older adults without cardiovascular disease, a QRSd >100 ms was significantly associated with incident HF. After adjustment for LV structural measures, the association was attenuated to non-significance, suggesting that prolonged QRSd is potentially a useful marker of LV structure that may predispose to HF risk.
Electrocardiogram; Heart failure; Magnetic resonance imaging; QRS duration
This study makes an important contribution by being one of the first to define the burden of clinically silent myocardial infarctions in the CKD community.
Unrecognized myocardial infarctions (UMIs) are common in the general population but have not been well studied in patients with chronic kidney disease (CKD). The purpose of this study was to determine the prevalence and prognosis for mortality of UMI among adults with CKD.
The current study included 18 864 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed a baseline examination including a 12-lead electrocardiogram (ECG). UMI was defined as the presence of myocardial infarction (MI) by Minnesota ECG classification in the absence of self-reported or recognized MI (RMI). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and albuminuria using albumin-to-creatinine ratio from a spot urine sample. All-cause mortality was assessed over a median 4 years of follow-up.
The prevalence of UMI was 4, 6, 6 and 13% among participants with eGFR levels of ≥60, 45–59.9, 30–44.9 and <30 mL/min/1.73m2, respectively, and 4, 5, 7 and 10% among participants with albuminuria levels of <10, 10–29.9, 30–299.9 and ≥300 mg/g, respectively. Compared to those with no MI, the multivariable adjusted hazard ratio for all-cause mortality associated with UMI and RMI was 1.65 [95% confidence interval (CI): 1.09–2.49] and 1.65 (95% CI: 1.20–2.26), respectively, among individuals with an eGFR <60 mL/min/1.73m2 and 1.49 (95% CI: 1.03–2.16) and 1.88 (95% CI: 1.40–2.52) among individuals with albuminuria ≥30 mg/g.
UMIs are common among individuals with an eGFR <60 mL/min/1.73m2 and albuminuria and associated with an increased mortality risk.
chronic kidney disease; coronary artery disease; mortality
Stroke symptoms are common among people without a history of stroke or transient ischemic attack; however, it is unknown if particular attention should be focused on specific symptoms for subgroups of patients.
Using baseline data from 26,792 REasons for Geographic and Racial Differences in Stroke (REGARDS) participants without a history of transient ischemic attack or stroke, we assessed the association between age, sex, race, current smoking, hypertension and diabetes and the six stroke symptoms in the Questionnaire for Verifying Stroke-Free Status.
The mean age of participants was 64.4 ± 9.4 years, 40.7% were black and 55.2% women. After multivariable adjustment, older persons more often reported an inability to understand (odds ratio [OR] = 1.16 per 10 years older age, 95% confidence interval [CI]: 1.07–1.25) and unilateral vision loss (OR=1.09, 95% CI: 1.01–1.18) and less often reported numbness (OR=0.83, 95% CI: 0.79–0.87) and weakness (OR=0.85, 95% CI: 0.80–0.90). Women reported difficulty communicating more often than men (OR=1.36, 95% CI: 1.19–1.56). The OR for blacks compared to whites for each of the six stroke symptoms was increased, markedly so for unilateral numbness (OR=1.97, 95% CI: 1.81–2.16), unilateral weakness (OR=1.96, 95% CI: 1.76–2.18) and inability to understand (OR=1.87, 95% CI: 1.61–2.18). Current smoking, hypertension, and diabetes were associated with higher ORs for each stroke symptom.
The association of risk factors with six individual stroke symptoms studied was not uniform, suggesting the need to emphasize individual stroke symptoms in stroke awareness campaigns when targeting populations defined by risk.
individual stroke symptoms; stroke symptoms; risk factors
Reduced heart rate variability (HRV) in older patients with heart failure (HF) is common and indicates poor prognosis. Exercise training (ET) has been shown to improve HRV in younger patients with HF. However the effect of ET on HRV in older patients with HF is not known.
Methods and Results
Sixty-six participants (36% males), age 69±5 years, with HF and both preserved ejection fraction (HFPEF) and reduced ejection fraction (HFREF), were randomly assigned to 16 weeks of supervised ET (ET group) versus attention-control (AC group). Two HRV parameters (the standard deviation of all normal RR intervals (SDNN) and the root mean square of successive differences in normal RR intervals (RMSSD)) were measured at baseline and after completion of the study. When compared with the AC group, the ET group had a significantly greater increase in both SDNN (15.46 ± 5.02 ms in ET versus 2.37 ± 2.13 ms in AC, P = 0.016), and RMSSD (17.53 ± 7.83 ms in ET versus 1.69 ± 2.63 ms in AC, P = 0.003). This increase was seen in both genders and HF categories.
ET improves HRV in older patients with both HFREF and HFPEF.
Atrial fibrillation and obesity are increasing in prevalence and are inter-related epidemics. There has been limited assessment of how obesity and the metabolic syndrome impact P wave indices, established electrocardiographic predictors of atrial fibrillation. We conducted a cross-sectional analysis to determine the association of obesity and the components of the metabolic syndrome with P wave indices in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Analyses were adjusted for demographic, anthropometric, and clinical variables and cardiovascular diseases and risk factors. Following relevant exclusions, 14,433 subjects were included (55% women and 24.7% black). In multivariable analyses, we identified significant, progressive increases in PR interval, P wave maximum duration, and P wave terminal force with BMI 25–30 kg/m2 and BMI ≥30 kg/m2 compared to the reference group <25 kg/m2 (P<0.0001 for trend for all P wave indices). These effects were present in both blacks and whites. Presence of metabolic syndrome was also associated with longer P wave indices. When components of the metabolic syndrome were examined separately, hypertension resulted in significant (P<0.001) augmentation of the three P wave indices. Similarly, waist circumference was associated with greater P wave maximum duration in both races (p<0.001). We concluded that P wave indices are significantly associated with obesity and particularly with hypertension and waist circumference. P wave indices may comprise intermediate markers, independent of age and cardiovascular risk, of the pathway linking obesity and with the risk of AF.
P waves; obesity; metabolic syndrome; epidemiology
We evaluated predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) study.
Methods and Results
The study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from Cox regression with 95% confidence intervals were computed for 18 dichotomized repolarization‐related ECG variables. The average follow‐up was 14 years. Independent predictors of CHD death in men were TaVR‐ and rate‐adjusted QTend (QTea), with a 2‐fold increased risk for both, and spatial angles between mean QRS and T vectors and between Tpeak (Tp) and normal R reference vectors [θ(Rm|Tm) and θ(Tp|Tref), respectively], with a >1.5‐fold increased risk for both. In women, independent predictors of the risk of CHD death were θ(Rm|Tm), with a 2‐fold increased risk for θ(Rm|Tm), and θ(Tp|Tref), with a 1.7‐fold increased risk. Independent predictors of SCD in men were θ(Tp|Tref) and QTea, with a 2‐fold increased risk, and θ(Tinit|Tterm), with a 1.6‐fold increased risk. In women, θ(Tinit|Tterm) was an independent predictor of SCD, with a >3‐fold increased risk, and θ(Rm|Tm) and TV1 were >2‐fold for both.
θ(Rm|Tm) and θ(Tp|Tref), reflecting different aspects of ventricular repolarization, were independent predictors of CHD death and SCD, and TaVR and TV1 were also independent predictors. The risk levels for independent predictors for both CHD death and SCD were stronger in women than in men, and QTea was a significant predictor in men but not in women.
electrocardiography; ischemic heart disease; prognosis; repolarization; sudden death
Both metaxbolic syndrome (MS) and atrial fibrillation (AF) are associated with increased cardiovascular disease morbidity and mortality. This analysis evaluates the association between MS and AF in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MS was defined using criteria recommended in the joint interim statement from several international societies. AF was defined in two ways - by electrocardiogram (ECG) and/or self-report and by ECG alone. Among individuals with 0, 1, 2, 3, 4 and 5 MS components, the prevalence of AF by ECG and/or self-report was 5.5%, 7.7%, 8.2%, 9.2%, 9.6% and 11.5%, respectively (p-trend<0.001). After multivariable adjustment, each of the MS components except serum triglycerides was significantly associated with AF. The multivariable-adjusted odds ratio for AF, defined by ECG and/or or self-reported history, comparing those with versus without MS was 1.20 (95% CI: 1.10 – 1.29). Results were consistent when AF was defined by ECG alone (OR=1.15, 95% CI: 0.92 – 1.39). In conclusion, MS is associated with an increased prevalence of AF. Further studies investigating a potential mechanism for this excess risk are warranted.
Atrial Fibrillation/epidemiology; Metabolic Syndrome X/epidemiology; Adults; Humans; Cohort Studies
To examine the association between prolongation of heart rate–corrected QT interval (QTc) with incident stroke.
Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.
A total of 27,411 participants aged ≥ 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median 5.1 years).
The risk of incident stroke in study participants with prolonged QTcFram was almost three times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for demographics (age, race, sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QT-prolonging drugs, the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0061)], and was consistent across several subgroups of REGARDS participants. Similar results were obtained when the risk of stroke was estimated per 1-standard deviation increase in QTcFram, [HR (95% CI): 1.12 (1.03, 1.21), p=0.0053 in multivariable-adjusted model], and when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used.
QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QT-prolonging drugs may be warranted.
QTc; stroke; electrocardiogram; QT-prolonging drugs; REGARDS
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
The association between metabolic syndrome and electrocardiographic (ECG) abnormalities is not well established.
ECG tracings of 6,765 men and women aged 45–84 years, free of clinical cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis were obtained (2000–2002) and classified as normal or having major or minor abnormalities. We evaluated the associations of metabolic syndrome and its components with ECG abnormalities, adjusting for age, ethnicity, and gender and testing for effect modification by ethnicity and gender.
The associations of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied significantly by gender. In males, metabolic syndrome and hypertension were significantly associated with major ECG abnormality [1.69 (1.33–2.13), and 2.22 (1.72–2.86), respectively] after adjusting for ethnicity and gender. Hypertension was also associated significantly with minor ECG abnormality in males after adjusting for age and ethnicity. In females, metabolic syndrome and hypertension were significantly associated with major [1.84 (1.44–2.37), and 1.68 (1.27–2.22), respectively] and minor [1.38 (1.19–1.59), and 1.53 (1.32–1.79), respectively] ECG abnormalities after adjusting for age and ethnicity. High triglycerides were only significantly associated with major ECG abnormality in females after adjusting for age and ethnicity. After adjusting for age, ethnicity, and gender, central obesity and high fasting blood glucose were significantly associated with major and minor ECG abnormalities, whereas low high-density lipoprotein cholesterol was significantly associated with major ECG abnormality only.
Metabolic syndrome and its components are associated with major and/or minor ECG abnormalities. The relationship of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied according to gender.
Routine electrocardiograms (ECGs) are not recommended for asymptomatic patients because the potential harms are thought to outweigh any benefits. Assessment tools to identify high risk individuals may improve the harm versus benefit profile of screening ECGs. In particular, people with unrecognized myocardial infarction (UMI) have elevated risk for cardiovascular events and death.
Using logistic regression, we developed a basic assessment tool among 16,653 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study using demographics, self-reported medical history, blood pressure, and body mass index and an expanded assessment tool using information on 51 potential variables. UMI was defined as electrocardiogram evidence of myocardial infarction without a self-reported history (n = 740).
The basic assessment tool had a c-statistic of 0.638 (95% confidence interval 0.617 - 0.659) and included age, race, smoking status, body mass index, systolic blood pressure, and self-reported history of transient ischemic attack, deep vein thrombosis, falls, diabetes, and hypertension. A predicted probability of UMI > 3% provided a sensitivity of 80% and a specificity of 30%. The expanded assessment tool had a c-statistic of 0.654 (95% confidence interval 0.634-0.674). Because of the poor performance of these assessment tools, external validation was not pursued.
Despite examining a large number of potential correlates of UMI, the assessment tools did not provide a high level of discrimination. These data suggest defining groups with high prevalence of UMI for targeted screening will be difficult.
Myocardial infarction; Screening; Electrocardiography
Our aim was to determine if silent myocardial infarction (MI) is more common in women with type 2 diabetes than in men. Our secondary aim was to examine the relationships between silent MI and risk factors for cardiovascular disease.
Research Design and Methods
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) database was used to determine if women had more silent MI on baseline electrocardiograms (ECGs) than did men with a similar unremarkable cardiovascular history. MI was diagnosed using ECG analysis according to the Minnesota code. Multivariable logistic regression analysis was used to compare demographic and clinical associations. Interactive effects of risk factors by gender were tested using a forward selection algorithm.
Men were found to have a higher prevalence of silent MI on baseline ECGs than women (6% vs 4%, p=0.001). Women had lower odds of silent MI than men after adjusting for other risk factors (OR=0.80, p=0.04). Race and ethnicity were significantly associated with silent MI (p=0.02), with Asians having the highest and African Americans and Hispanics having lower odds relative to whites.
Our main findings provide no evidence that silent MI, as detected by the Minnesota code, was more common in women than in men in the ACCORD cohort. If, as in the general population, the women in ACCORD are found to have a higher heart disease mortality rate than the men, it seems unlikely that failure to recognize clinically silent heart disease in the years before study enrollment could be a major cause.
silent myocardial infarction; type 2 diabetes; Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial; cardiovascular disease in women
While black-white and regional disparities in U.S. stroke mortality rates are well documented, the contribution of disparities in stroke incidence is unknown. We provide national estimates of stroke incidence by race and region, contrasting these to publicly available stroke mortality data.
This analysis included 27,744 men and women without prevalent stroke (40.4% black), aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study, enrolled 2003–2007. Incident stroke was defined as first occurrence of stroke over 4.4 years of follow-up. Age-sex–adjusted stroke mortality rates were calculated using data from the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) System.
There were 460 incident strokes over 113,469 person-years of follow-up. Relative to the rest of the United States, incidence rate ratios (IRRs) of stroke in the southeastern stroke belt and stroke buckle were 1.06 (95% confidence interval [CI], 0.87–1.29) and 1.19 (95% CI, 0.96–1.47), respectively. The age-sex–adjusted black/white IRRblack was 1.51 (95% CI, 1.26–1.81), but for ages 45–54 years the IRRblack was 4.02 (95% CI, 1.23–13.11) while for ages 85+ it was 0.86 (95% CI, 0.33–2.20). Generally, the IRRsblack were less than the mortality rate ratios (MRRs) across age groups; however, only in ages 55–64 years and 65–74 years did the 95% CIs of IRRsblack not include the MRRblack. The MRRs for regions were within 95% CIs for IRRs.
National patterns of black-white and regional differences in stroke incidence are similar to those for stroke mortality; however, the magnitude of differences in incidence appear smaller.
Various hemostatic markers are associated with the risk of cardiovascular disease; however, limited information exists on their relationship with the occurrence and prognosis of atrial fibrillation (AF).
To assess whether hemostatic markers are associated with the incidence and prognosis of AF.
We studied 14,858 men and women in the Atherosclerosis Risk in Communities cohort, aged 45–64 and free of AF at baseline (1987–1989). Fibrinogen, von Willebrand factor (vWf), factor VII activity (VIIc), factor VIII activity (VIIIc), protein C, antithrombin III (ATIII), and activated partial thromboplastin time (aPTT) were measured in blood samples at baseline. AF and other cardiovascular outcomes through 2005 were determined following standardized protocols.
During a median follow-up of 16.8 years, 1209 cases of AF were identified. In multivariable Cox models, the hazard ratios (HR) and 95% confidence intervals (CI) of incident AF associated with a 1-standard deviation (SD) increase in each marker were 1.13 (1.07–1.20) for fibrinogen, 1.17 (1.11–1.23) for vWf, 1.17 (1.11–1.24) for factor VIIIc, 0.93 (0.88–1.00) for factor VIIc, 0.98 (0.92–1.04) for protein C, 1.00 (0.94–1.06) for aPTT and 1.00 (0.95–1.06) for ATIII. Greater factor VIIIc, fibrinogen and vWf were consistently associated with a higher risk of cardiovascular outcomes and mortality in those with and without incident AF, while greater protein C was associated with a lower risk of ischemic stroke.
Several hemostatic markers are associated with the incidence of AF independently of other cardiovascular risk factors. Their role in the risk stratification of AF patients should be further studied.
atrial fibrillation; epidemiology; prognosis; fibrinogen; von Willebrand factor
To compare cardiac autonomic function as measured by heart rate variability for HIV-infected participants taking protease inhibitors (PIs) with those taking a non-nucleoside reverse transcriptase inhibitor without a PI (NNRTI-no PI) regimen.
2998 participants (average age 44 years, 28% females) enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial.
Primary outcome measures
Heart rate and two heart rate variability measures (the SD of all filtered RR intervals over the length of the recording (SDNN) and the root mean square of successive differences in normal RR intervals (rMSSD)).
At study entry, 869 participants were taking a boosted PI (PI/r), 579 a non-boosted PI and 1550 an NNRTI-no PI. Median values (IQR) of heart rate, SDNN and rMSSD were: 68 (60–75) beats/min (bpm), 21 (13–33) ms, 22 (13–35) ms in the PI/r group, 68 (60–75) bpm, 21 (13–33) ms and 21 (14–33) ms in the non-boosted PI group and 69 (62–77) bpm, 20 (13–31) ms and 21(13–33) ms in the NNRTI-no PI group. After adjustment for baseline factors, for those given PI/r and non-boosted PI, heart rate was 2.2 and 2.8 bpm, respectively, lower than the NNRTI-no PI group (p<0.001 for both). On the other hand, compared with the NNRTI-no PI group, log SDNN and log rMSSD were significantly greater for those in the non-boosted PI (p values for baseline adjusted differences in log-transformed SDNN and rMSSD were 0.004 and 0.001) but not for those in the PI/r group at the 0.01 α-level.
Compared to an NNRTI-no PI regimen, heart rate was lower for those taking a PI/r or non-boosted PI and heart rate variability was greater, reflecting better cardiac autonomic function, for those taking a non-boosted PI regimen but not PI/r.
Virology; Cardiology; Clinical Pharmacology
Data are sparse describing factors associated with development of prolonged QRS duration (QRSd) from young adulthood to middle age.
We analyzed 12-lead electrocardiograms (ECGs) from the Coronary Artery Risk Development in Young Adults (CARDIA) study over 20 years. We performed logistic regression to examine associations of baseline (Year 0) or average (Year 0 to Year 20) risk factors with incident prolonged QRSd (QRS > 100 msec).
We included 2,537 participants (57.2% women, 44.7% black, mean age 25 years); 292 (11.5%) developed incident QRSd >100 msec by Year 20. In univariate analyses, baseline covariates associated with incident QRSd prolongation included white race, male sex, ECG-LVMI, and baseline QRSd. Similar results were observed after multivariable adjustment.
We found no long-term associations of modifiable risk factors with incident QRSd >100 msec. Men, whites, and those with higher ECG-LVMI and QRSd in young adulthood are at increased risk for incident prolonged QRSd by middle age.
Individuals with unrecognized myocardial infarction (UMI) have similar risks for cardiovascular events and mortality as those with recognized myocardial infarction (RMI). The prevalence of cardioprotective medication use and blood pressure and low-density lipoprotein cholesterol control among individuals with UMI is unknown.
Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were recruited between May 2004 and October 2007 received baseline twelve-lead electrocardiograms (n = 21,036). Myocardial infarction (MI) status was characterized as no MI, UMI (electrocardiogram abnormalities consistent with MI without self-reported history; n = 949; 4.5%), and RMI (self-reported history of MI; n = 1574; 7.5%).
For participants with no MI, UMI, and RMI, prevalence of use was 38.4%, 44.4%, and 75.7% for aspirin; 18.0%, 25.8%, and 57.2% for beta blockers; 31.7%, 38.7%, and 55.0% for angiotensin converting enzyme inhibitors or angiotensin receptor blockers; and 28.1%, 33.9%, and 64.1% for statins, respectively. Participants with RMI were 35% more likely to have low-density lipoprotein cholesterol < 100 mg/dL than participants with UMI (prevalence ratio = 1.35, 95% confidence interval 1.19–1.52). Blood pressure control (,140/90 mmHg) was similar between RMI and UMI groups (prevalence ratio = 1.03, 95% confidence interval 0.93–1.13).
Although participants with UMI were somewhat more likely to use cardioprotective medications than those with no MI, they were less likely to use cardioprotective medications and to have controlled low-density lipoprotein cholesterol than participants with RMI. Increasing appropriate treatment and risk factor control among individuals with UMI may reduce risk of mortality and future cardiovascular events.
unrecognized myocardial infarction; secondary prevention; risk factor control
Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid lowering medication use with AF risk.
Methods and Results
We analyzed 13,969 participants (25% African-American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities (ARIC) study. Fasting HDL cholesterol (HDLc), LDL cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987–89) and each of three follow-up visits. Incidence of AF was ascertained through 2007. The association of the use of statins and other lipid lowering medications with AF was estimated in 13,044 ARIC participants attending visit 2 (1990–92), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years there were 1433 incident AF cases. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) of AF associated with a one standard deviation increase in lipid levels were: HDLc: 0.97 (0.91–1.04); LDLc: 0.90 (0.85–0.96); total cholesterol: 0.89 (0.84–0.95); and triglycerides: 1.00 (0.96–1.04). Participants taking lipid lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82–1.13) compared to those not on medications, while those taking statins had an adjusted HR of 0.91 (0.66–1.25) compared to those taking other lipid lowering mediations.
Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. HDLc and triglycerides, however, were not independently associated with AF incidence. No association was found between the use of lipid lowering medications and incident AF.
lipids; epidemiology; atrial fibrillation; statins
Background and Purpose
Black/white disparities in stroke incidence are well-documented, but few studies have assessed the contributions to the disparity. Here we assess the contribution of “traditional” risk factors.
25,714 black and white men and women, aged 45+ and stroke-free at baseline were followed for an average of 4.4 years to detect stroke. Mediation analysis employing proportional hazards analysis assessed the contribution of “traditional” risk factors to racial disparities.
At age 45, incident stroke risk was 2.90 (95% CI: 1.72 – 4.89) times more likely in blacks than whites, and 1.66 (95% CI: 1.34 – 2.07) times at age 65. Adjustment for risk factors attenuated these excesses by 40% and 45%, respectively, resulting in relative risks of 2.14 (95% CI: 1.25 – 3.67) and 1.35 (95% CI: 1.08 – 1.71). Approximately one-half of this mediation is attributable to systolic blood pressure. Further adjustment for socioeconomic factors resulted in total mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16 – 3.47) and 1.30 (1.03 – 1.65) respectively.
Between ages 45 to 65 years, approximately half of the racial disparity in stroke risk is attributable to traditional risk factors (primarily systolic blood pressure) and socioeconomic factors, suggesting a critical need to understand the disparity in the development of these traditional risk factors. Because half of the excess stroke risk in blacks is not attributable to traditional risk factors and socioeconomic factors, differential racial susceptibility to risk factors, residual confounding or non-traditional risk factors may also play a role.
stroke; risk factors; hypertension; diabetes; mediation analysis
An association has been described between death from arrhythmia and early repolarization, an electrocardiogram pattern characterized by elevation of the QRS–ST junction (J-point). Little is known about this relationship in non-white populations. This study examines the relationship between J-point elevation (JPE) and sudden cardiac death (SCD) and whether this relationship differs by race or sex.
Methods and results
A total of 15 141 middle-aged subjects from the prospective, population-based Atherosclerosis Risk in Communities (ARIC) study were included in this analysis. The primary endpoint was physician-adjudicated SCD occurring from baseline (1987–1989) through December 2002, secondary endpoints were fatal and non-fatal coronary events and all-cause mortality occurring through December 2007. J-point elevation was defined as J-point amplitude ≥0.1 mV. Pre-specified subgroup analyses by sex and race were conducted. J-point elevation in any lead was present in 1866 subjects (12.3%). After adjustment for demographic, clinical, lifestyle, and laboratory variables, JPE was not significantly related to SCD in the overall sample [adjusted hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.87–1.75]. However, significant interactions were present between race and JPE (P = 0.006) and between sex and JPE (P = 0.020). J-point elevation was significantly predictive of SCD in whites (adjusted HR, 2.03; 95% CI, 1.28–3.21) and in females (adjusted HR, 2.54; 95% CI, 1.34–4.82).
Our results suggest that JPE is associated with an increased risk of SCD in whites and in females, but not in blacks or males. Further studies are needed to clarify which subgroups of individuals with JPE are at increased risk for adverse cardiac events.
Electrocardiography; Sudden cardiac death; J-point elevation; Epidemiology
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