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Biomedical subjects

Pentti M Rautaharju

Publications and source records attributed to Pentti M Rautaharju.

At least 19 recordsLinked to original sources

Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort).

The clinical relevance of ventricular premature complexes (VPCs) in apparently healthy patients is not clear and is typically not considered when evaluating risk. We conducted a prospective longitudinal study of the population-based Atherosclerosis Risk In Communities (ARIC) study of 15,070 Caucasians and African-Americans, 45 to 64 years of age, to assess the risks of coronary heart disease (CHD) events and mortality associated with VPCs among participants with and without prevalent CHD at baseline. VPCs on a single 2-minute electrocardiogram were identified in 940 participants (6.2%). After a follow-up of >10 years, 1,762 participants died, with 366 deaths related to CHD, and 1,736 had cardiac events. The percentage of participants with CHD mortality was >3 times greater for those with VPCs compared with those without VPCs. After controlling for cardiovascular risk factors and therapy with proportional hazards regression, participants with VPCs were >2 times as likely to die due to CHD than were those without VPCs. Increased risk was found for participants with and without baseline CHD. In conclusion, a clinical finding of VPCs on electrocardiography of even apparently healthy patients may warrant a heightened awareness of and attention to cardiovascular risk assessment and management.

Coronary Disease↗

Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women's Health Initiative.

BACKGROUND: Information is limited about the independent prognostic value of repolarization abnormalities in women. METHODS AND RESULTS: We evaluated hazard ratios for ECG variables for combined fatal and nonfatal coronary heart disease (CHD) events and for CHD mortality using Cox regression in 38,283 Women's Health Initiative (WHI) participants during up to 9.2 years of follow-up. All risk models were adjusted for demographic, clinical, and therapeutic variables. Evaluated as single ECG variables, wide QRS/T angle and ECG-demonstrated myocardial infarction (ECG-MI) were the strongest predictors of CHD events, with hazard ratios (95% CI) of 1.90 (1.50 to 2.42) and 1.62 (1.29 to 2.03), respectively. Six other repolarization variables were also significant, strong predictors of CHD events. Wide QRS/T angle, ECG-MI, and QT prolongation appeared as dominant predictors when evaluated simultaneously with other ECG variables in a multiadjusted risk model. QRS/T angle, ECG-MI, and high QRS nondipolar voltage were the strongest predictors of CHD mortality, with hazard ratios of 2.70, 2.41, and 2.18, respectively. The risk increase ranged from 63% to 95% for the other 4 significant predictors. Five ECG abnormalities were identified as dominant mortality risk predictors: wide QRS/T angle, ECG-MI, high QRS nondipolar voltage, reduced heart rate variability, and QT prolongation (in the cardiovascular disease-free group only). CONCLUSIONS: Ventricular repolarization abnormalities in postmenopausal women are as important predictors of CHD events and CHD mortality as ECG-MI and other QRS abnormalities. Repolarization variables and QRS nondipolar voltage warrant attention in future investigations.

Aged↗

Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: the Women's Health Initiative.

BACKGROUND: Information is limited about ECG predictors of the risk of incident congestive heart failure (CHF), particularly in women without overt manifestations of cardiovascular disease (CVD). METHODS AND RESULTS: We evaluated hazard ratios for incident CHF and all-cause mortality using Cox regression in 38,283 participants of the Women's Health Initiative (WHI) during a 9-year follow-up. All risk models were adjusted for demographic and available clinical and therapeutic variables (multivariable-adjusted models). A backward selection procedure was used to identify dominant predictors among those that were significant as individual ECG predictors. Eleven ECG variables were significant predictors of incident CHF, with none of them having a significant interaction with baseline CVD status. From 6 dominant ECG predictors, wide QRS/T angle had a nearly 3-fold increased risk in multivariable-adjusted single ECG variable models. Two other repolarization variables, STV5 depression and high TV1 amplitude, and 2 QRS-related variables, QRS non-dipolar voltage and myocardial infarction (MI) by ECG, were all associated with &2-fold increase of incident CHF risk. Overall, 11 of the 12 ECG variables were significant predictors of all-cause mortality. Four variables had a significant interaction with CVD status requiring stratification. Three among these 4 were strong, dominant predictors in the CVD group: ECG MI, wide QRS/T angle, and low TV5 amplitude had risk increase from >2-fold to 3-fold, with considerably lower risks in the CVD-free group. CONCLUSIONS: Several repolarization variables in postmenopausal women are predictors of the risk of incident CHF and all-cause mortality as important as old ECG MI.

Age Distribution↗

Normal standards for QT and QT subintervals derived from a large ethnically diverse population of women aged 50 to 79 years (the Women's Health Initiative [WHI]).

Available normal standards for rate-adjusted QT intervals in women are based on samples that include only whites, and no normal standards are available for QT subintervals. This study derived normal limits from percentile distributions for QT as well as QT and T-wave subintervals in 22,311 participants in the Women's Health Initiative (WHI), including 19,059 white, 1,771 African-American, 819 Hispanic, 82 American Indian, and 580 Asian women. Excluded were women with cardiovascular disease or who were using cardioactive drugs at baseline and cardiovascular morbidity or death during the subsequent mean 6.3-year follow-up. Normal limits for QT adjusted by Bazett's formula were strongly rate dependent, invalidating their use in practical applications. QT adjusted as a linear function of RR (QTrr) or by power functions of RR with exponent 0.5 (QTsqr) or 0.42 (QT0.42) using an appropriate regression function produced rate-invariant upper and lower normal limits for rate-adjusted QT. Adjusted QT is preferable to adjusted JT because the latter requires the incorporation of QRS duration as a covariate with RR. Normal limits were also derived for T-wave subintervals. Normal limits of QTrr in Asian women were 10 ms longer than in other ethnic groups. In conclusion, QT adjusted for rate as a linear function of RR is preferable to JT and other QT subintervals in the evaluation of QT prolongation. The adaptation of considerable revisions of the currently used limits for prolonged QT in women is suggested, with an additional race-specific adjustment in Asian women. Bazett's formula is inappropriate for testing new drugs or other applications.

Black or African American↗

Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study).

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.

Aged↗

Dietary linolenic acid and adjusted QT and JT intervals in the National Heart, Lung, and Blood Institute Family Heart study.

OBJECTIVES: The goal of this study was to examine whether higher consumption of total linolenic acid was associated with rate-adjusted QT and JT intervals (QTrr and JTrr, respectively). BACKGROUND: Higher intake of fish omega-3 fatty acids and plant omega-3 such as alpha-linolenic acid is associated with lower risk of myocardial infarction. While long-chain omega-3 can inhibit ventricular arrhythmia, it is not known whether alpha-linolenic acid influences ventricular repolarization. METHODS: We studied 3,642 subjects from the National Heart, Lung, and Blood Institute Family Heart study who were free of myocardial infarction, left ventricular hypertrophy, pacemaker, and with QRS <120 ms. We used the 95th percentile of the gender-specific distribution of QTrr and JTrr to define abnormally prolonged repolarization. Within each gender, we created age- and energy-adjusted tertiles of linolenic acid and used regression models for analyses. RESULTS: Mean age was 50 years, and average intake of total linolenic acid was 0.74 g/day. There was an inverse association between consumption of linolenic acid and QTrr and JTrr (p for trend 0.001 and 0.0005, respectively). From the lowest (reference) to the highest gender-, age-, and energy-adjusted tertile of linolenic acid, multivariable adjusted odds ratios for prolonged QTrr were 1.0, 0.74 (95% confidence interval [CI] 0.57 to 0.96), and 0.59 (95% CI 0.44 to 0.77), respectively (p for trend 0.0003). Corresponding values for JTrr were 1.0, 0.73 (95% CI 0.52 to 1.03), and 0.59 (95% CI 0.40 to 0.87), respectively (p for trend 0.009). Exclusion of subjects taking drugs known to influence QT did not influence this association. CONCLUSIONS: Higher intake of dietary linolenic acid might be associated with a reduced risk of abnormally prolonged repolarization in men and women.

Adult↗

The association of spatial T wave axis deviation with incident coronary events. The ARIC cohort.

BACKGROUND: Although current evidence suggests that the spatial T wave axis captures important information about ventricular repolarization abnormalities, there are only a few and discordant epidemiologic studies addressing the ability of the spatial T wave axis to predict coronary heart disease (CHD) occurrence. METHODS: This prospective study analyzed data from 12,256 middle-aged African American and white men and women, from the Atherosclerosis Risk in Communities Study (ARIC). Following a standardized protocol, resting standard 12-lead, 10-second electrocardiograms were digitized and analyzed with the Marquette GE program. The median follow-up time was 12.1 years; incident coronary heart disease comprised fatal and non-fatal CHD events. RESULTS: The incidence rate of CHD was 4.26, 4.18, 4.28 and 5.62 per 1000 person-years respectively, across the spatial T wave axis quartiles. Among women for every 10 degrees increase in the spatial T wave axis deviation, there was an estimated increase in the risk of CHD of 1.16 (95% CI 1.04-1.28). After adjustment for age, height, weight, smoking, hypertension, diabetes, QRS axis and minor T wave abnormalities, this hazard rate ratio for women fell to 1.03 (0.92-1.14). The corresponding crude and adjusted hazard ratios for men were 1.05 (95% CI 0.96-1.15) and 0.95 (0.86-1.04) respectively. CONCLUSIONS: In conclusion, this prospective, population-based, bi-ethnic study of men and women free of coronary heart disease at baseline shows that spatial T wave axis deviation is not associated with incident coronary events during long-term follow up. It is doubtful that spatial T wave axis deviation would add benefit in the prediction of CHD events above and beyond the current traditional risk factors.

Black or African American↗

Short-term repeatability of electrocardiographic spatial T-wave axis and QT interval.

Although ventricular repolarization abnormalities reflect arrhythmic susceptibility, few reliable tools exist to identify their presence. We investigated the repeatability of the spatial T-wave axis and QT interval from standard 12-lead electrocardiograms in 63 asymptomatic volunteers. Certified technicians used a standardized protocol to digitally record 2 electrocardiograms per participant at each of 2 visits separated by 1 to 2 weeks. Absolute paired differences within and between visits were 0.19 degrees and 0.90 degrees for the T-wave axis and 1.08 and 1.55 milliseconds for the QT interval, respectively. The intraclass correlation coefficients for the T-wave axis and QT interval were 0.87 and 0.86, respectively. The impact of repeated measurements on the precision of the QT-interval measurements was evaluated for a hypothetical clinical trial aimed at detecting a drug-induced QT prolongation. We conclude that the spatial T-wave axis is as repeatable a measure of ventricular repolarization as the QT interval.

Electrocardiography↗

Assessment of prolonged QT and JT intervals in ventricular conduction defects.

The JT interval or Bazett's QTc - QRS has been advocated for detection of prolonged repolarization in ventricular conduction defects (VCDs). However, the use of neither JT nor QTc - QRS has been validated, and normal limits for rate-adjusted JT have not been established for VCDs or for normal ventricular conduction. Functional relations among RR, JT, and QT intervals were evaluated in 11,739 adult men and women with normal ventricular conduction and in 1,251 subjects with major VCD. The results showed that JT adjustment obtained as QTc - QRS retained a strong residual correlation with ventricular rate (r = 0.54), making its use ill-advised. In contrast, QT adjustment as a linear function of the RR interval for VCD as QT(RR,QRS) = QT - 155 x (60/heart rate - 1) - 0.93 x (QRS - 139) + k, with k = -22 ms for men and -34 ms for women, removed the rate dependence and produced upper 2% and 5% normal limits at 460 and 450 ms, respectively, which are identical to those in normal conduction. As an alternative, equally effective linear JT adjustment formulas were derived, including newly required normal standards. Thus, detection of prolonged repolarization in VCD requires the use of the JT interval or a bivariate model for QT with RR and QRS intervals as covariates.

Adult↗

The association between the length of the QT interval and mortality in the Cardiovascular Health Study.

PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7). CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.

Aged↗

Prospective association between hormone replacement therapy, heart rate, and heart rate variability. The Atherosclerosis risk in communities study.

Hormone replacement therapy is universally associated with coronary heart disease (CHD) in observational studies, but it is unknown whether this association is mediated by the autonomic nervous system. We tested the hypothesis that postmenopausal hormone replacement therapy was associated with more favorable heart rate (HR) and heart rate variability (HRV) in a population sample of women (n=2,621). Hormone therapy use was measured at four examinations beginning in 1987. Supine HR and HRV indices were measured for 6 minutes at the final examination (1996-1998). In unadjusted linear regression models, hormone therapy was associated with lower HR (hormone use=64.7 vs. never=65.7 beats/min, P=.01) and higher HRV. However, following adjustment for age and CHD risk factors, both associations were eliminated. Results from this observational study suggest that hormone therapy is not associated with HR or HRV. These analyses should be replicated in a randomized trial.

Autonomic Nervous System↗

A prospective evaluation of the risk of QT prolongation with hormone replacement therapy: the atherosclerosis risk in communities study.

PURPOSE: Prolongation of the QT interval is associated with an increased risk of arrhythmia, coronary heart disease (CHD), and mortality. Estrogens and androgens have been proposed as a causal factor in QT lengthening. We tested whether postmenopausal hormone replacement therapy was associated with prolonged QT intervals in a healthy population sample of women (mean age=54). METHODS: Women (n=3103) were asked about estrogen (ERT) and progestin plus estrogen (PERT) replacement therapy use at 4 examinations over 9 years. Electrocardiographic QT intervals were measured and corrected for heart rate using the QT Index (QTI) and Bazett's correction. QT prolongation was defined as QTI>110% and a change from baseline of >or=4%. RESULTS: Heart rate corrected QT length was moderately but significantly (p<0.01) greater, and the risk of QT prolongation was nearly twice (Odds Ratio=1.9, 95% Confidence Interval: 1.2-2.0) that in women who used ERT compared with never users. PERT use was not significantly associated with QT length. CONCLUSIONS: The potential for slight increases in QT length over time, and an increased risk of QT prolongation with ERT use identified in this observational study, are important concerns that should be further explored in randomized trials.

Arteriosclerosis↗