ECG left ventricular hypertrophy is a stronger risk factor for incident cardiovascular events in women than in men in the general population.

OBJECTIVE: Left ventricular hypertrophy (LVH) is a strong risk factor for cardiovascular events. ECG is the most widely used method for LVH detection. Despite the abundance of ECG LVH criteria, their prognostic values have been compared in only a few studies, and little has been known about how sex modifies the prognostic value of LVH. We assessed the relationship between ECG LVH and incident cardiovascular events in the general population. METHODS: Several ECG LVH criteria were measured in 3059 women and 2456 men participating in the Health 2000 Study - a national general population survey. Association between ECG LVH and cardiovascular events were analyzed with Cox proportional-hazards models. RESULTS: ECG LVH was more prevalent in women than in men when measured with Cornell-based criteria, but less prevalent or nondifferent when measured with other criteria. The association between ECG LVH and events showed higher hazard ratios for women than in men. Sex × LVH interaction terms were statistically significant in part of the LVH criteria. In adjusted Cox models, Sokolow-Lyon voltage performed the best. The composite of Sokolow-Lyon voltage and Cornell voltage was statistically significantly associated with events in both sexes. CONCLUSION: Sex affects both the prevalence rates and prognostic values of ECG LVH criteria in the general population, while showing higher prognostic value of ECG LVH in women than in men. For clinical use, the composite of the Sokolow-Lyon voltage and the Cornell voltage seems to be a good option.

Sensitivity and specificity of automated detection of early repolarization in standard 12-lead electrocardiography.

BACKGROUND: Early repolarization (ER) is defined as an elevation of the QRS-ST junction in at least two inferior or lateral leads of the standard 12-lead electrocardiogram (ECG). Our purpose was to create an algorithm for the automated detection and classification of ER. METHODS: A total of 6,047 electrocardiograms were manually graded for ER by two experienced readers. The automated detection of ER was based on quantification of the characteristic slurring or notching in ER-positive leads. The ER detection algorithm was tested and its results were compared with manual grading, which served as the reference. RESULTS: Readers graded 183 ECGs (3.0%) as ER positive, of which the algorithm detected 176 recordings, resulting in sensitivity of 96.2%. Of the 5,864 ER-negative recordings, the algorithm classified 5,281 as negative, resulting in 90.1% specificity. Positive and negative predictive values for the algorithm were 23.2% and 99.9%, respectively, and its accuracy was 90.2%. Inferior ER was correctly detected in 84.6% and lateral ER in 98.6% of the cases. CONCLUSIONS: As the automatic algorithm has high sensitivity, it could be used as a prescreening tool for ER; only the electrocardiograms graded positive by the algorithm would be reviewed manually. This would reduce the need for manual labor by 90%.

Office, home, and ambulatory blood pressures as predictors of cardiovascular risk.

Ambulatory blood pressure (BP) is considered as the gold standard of BP measurement although it has not been shown to be more strongly associated with cardiovascular risk than is home BP. Our objective was to compare the prognostic value of office, home, and ambulatory BP for cardiovascular risk in 502 participants examined in 1992 to 1996. The end point was a composite of cardiovascular mortality, myocardial infarction, stroke, heart failure hospitalization, and coronary intervention. We assessed the prognostic value of each BP in multivariable-adjusted Cox models. The likelihood χ2 ratio value was used to test whether the addition of a BP variable improved the model's goodness of fit. After a follow-up of 16.1±3.9 years, 70 participants (13.9%) had experienced ≥1 cardiovascular event. Office (systolic/diastolic hazard ratio per 1/1 mm Hg increase in BP, 1.024/1.018; systolic/diastolic 95% confidence interval, 1.009­1.040/0.994­1.043), home (hazard ratio, 1.029/1.028; 95% confidence interval, 1.013­1.045/1.005­1.052), and 24-hour ambulatory BP (hazard ratio, 1.033/1.049; 95% confidence interval, 1.019­1.047/1.023­1.077) were predictive of cardiovascular events. When all 3 BP variables were included in the model simultaneously, only systolic/diastolic ambulatory BP was a significant predictor of cardiovascular events (P=0.002/<0.001). Home systolic/diastolic BP improved the fit of the model only marginally when added to a model including office BP (χ2=3.0/4.0, P=0.09/0.047). Ambulatory BP, however, improved the fit of model more clearly when added to office and home BP (χ2=9.0/12.3, P=0.001/<0.001). Our findings suggest that ambulatory BP is prognostically superior to office and home BP.

Lack of impact of a comprehensive intervention on hypertension in the primary care setting.

BACKGROUND: The implementation of lifestyle modifications, home blood pressure (BP) measurement, and optimization of antihypertensive drug therapy have been shown to improve BP control in tightly controlled research settings. Our objective was to determine the effect of these interventions in a primary care setting, with the family practitioners and nurses serving as the interventionists. METHODS: Two hundred twenty hypertensive patients were recruited from 2 health centers that operated in the same building and covered similar populations, with the health centers randomized to function as intervention or control sites. Participants in the intervention group received repeated individual and group counseling from the centrally trained staff of the health center on healthy lifestyles. In addition, their antihypertensive drug therapy was guided by home BP measurements performed at 3-month intervals instead of by conventional office measurements. RESULTS: After 12 months of follow-up, the between-group differences in the changes of lifestyle variables (body mass index, physical activity, dietary recalls, and urinary sodium/potassium) were nonsignificant. Antihypertensive treatment intensity increased in both groups, but the between-group difference was nonsignificant (P = 0.63). Office systolic/diastolic BP decreased significantly in the intervention (8/6 mm Hg; P < 0.001) and control (11/7 mm Hg; P < 0.001) groups, but the between-group differences were nonsignificant (P = 0.25/0.16). CONCLUSIONS: Our intervention did not improve BP control as suggested by many prior studies performed in controlled academic settings. This result could be attributed to a lack of motivation and incentives among the staff or because the population was relatively unselected. Greater attention to education and financial incentives might be required in typical primary care settings to obtain better results. CLINICALTRIALSGOV IDENTIFIER: NCT01915199.

Risk assessment of echocardiographic left ventricular hypertrophy with electrocardiography, body mass index and blood pressure.

AIMS: Electrocardiography (ECG) has a high specificity but unfortunately low sensitivity to detect anatomic left ventricular hypertrophy (LVH). In this study, ECG amplitude and products were examined as continuous variables together with blood pressure (BP) and body mass index (BMI) to find out a simple method to predict echocardiographic (ECHO)-LVH. An age- and gender-stratified population-based sample of men (n = 121) and women (n = 135) aged 35-64 years enriched with newly diagnosed untreated hypertensive men (n = 138) and women (n = 97) in the Turku area in south-western Finland was studied. MAJOR FINDINGS: Cornell voltage (or Cornell product), systolic BP (SBP) and BMI were all independent determinants of ECHO-LVH and left ventricular mass (LVM) indexed by height (LVMI). According to multivariate regression analyses with Cornell voltage (Cornell product), BMI and BP as explanatory variables, the three determinants explained 46-48% (47-49%) of the variation in LVMI among men and 50-54% (52-57%) among women. Score tables were constructed to estimate the probability of LVH. The estimated probability of ECHO-LVH increased in men gradually from 0% to 81% (79%) along with increased Cornell voltage (Cornell product) tertiles and in women respectively from 0% to 95% (97%). CONCLUSION: The sensitivity of ECG to detect ECHO-LVH can be markedly enhanced by using ECG amplitudes and products as continuous variables. The risk tables using Cornell voltages or products, BMI and SBP enable an easy and effective way to estimate the probability of ECHO-LVH.

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance.

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45 years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P < 0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P < 0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.

High prevalence of four long QT syndrome founder mutations in the Finnish population.

AIMS: Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%-0.05%. In Finland, four founder mutations constitute up to 70% of the known genetic spectrum of LQTS. In the present survey, we sought to estimate the actual prevalence of the founder mutations and to determine their effect sizes in the general Finnish population. METHODS AND RESULTS: We genotyped 6334 subjects aged > or =30 years from a population cohort (Health 2000 study) for the four Finnish founder mutations using Sequenom MALDI-TOF mass spectrometry. The electrocardiogram (ECG) parameters were measured from digital 12-lead ECGs, and QT intervals were adjusted for age, sex, and heart rate using linear regression. A total of 27 individuals carried one of the founder mutations resulting in their collective prevalence estimate of 0.4% (95% CI 0.3%-0.6%). The KCNQ1 G589D mutation (n=8) was associated with a 50 ms (SE 7.0) prolongation of the adjusted QT interval (P=9.0x10(-13)). The KCNH2 R176W variant (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.1x10(-6)). CONCLUSION: In Finland 1 individual out of 250 carries a LQTS founder mutation, which is the highest documented prevalence of LQTS mutations that lead to a marked QT prolongation.

Pupillary function in early multiple sclerosis.

Autonomic pupillary function was assessed with pupillometry in 95 mildly or moderately disabled patients with multiple sclerosis (MS) and 81 healthy subjects. The parasympathetic pupillary function was measured as initial diameter (mm), time to minimum diameter (seconds), reflex amplitude (mm), relative reflex amplitude (%), and maximal constriction velocity (mm/seconds). To reflect the sympathetic pupillary function maximal redilatation velocity (mm/seconds), and time of 75% of redilatation (seconds) were measured. Of MS patients 85-99% were within the reference values of healthy subjects. In MS patients the effect of age was observed in the initial diameter, reflex amplitude, and time of 75% redilatation. There were no such age related effects in healthy subjects. In age adjusted analysis the initial diameter and time of 75% redilatation differed significantly from healthy controls. Autonomic pupillary functions were not associated with fatigue, visual defect, or bladder disturbance, as measured by Fatigue Severity Scale, Kurtzke's Functional System Scales, Expanded Disability Status Scale, or the Multiple Sclerosis Functional Composite. Our results suggest that both parasympathetic and sympathetic pupillary functions are disturbed already early in the course of MS. However, the disturbance is not severe at this stage of the disease. The dysfunction is age-dependent and thus possibly related to the dimished remyelination capacity of the central nervous system.

Changes in cardiovascular autonomic regulation among elderly subjects: follow-up of sixteen years.

BACKGROUND: Previous cross-sectional studies have suggested that cardiac autonomic regulation, measured as heart rate (HR) variability, is altered upon ageing, and that altered HR variability may predict mortality. However, there are no longitudinal follow-up reports of the changes of HR dynamics in elderly subjects. AIM & METHOD: This study was designed to examine the longitudinal changes in the spectral, fractal, and complexity measures of HR variability in a random sample of 41 elderly subjects (mean age 69+/-4 years), who underwent repeated 24-hour Holter recordings at the baseline and after 16 years' follow-up. Several cardiovascular risk factors were determined at the baseline. RESULTS: A time-domain index, standard deviation of N-N intervals (SDNN) (142+/-34 msec versus 133+/-50 msec, not significant (NS)), and the high frequency spectral component of HR variability (219+/-222 msec(2)versus 268+/-287 msec(2), NS) did not change during the follow-up. The low frequency power (LF) of HR variability decreased from 678+/-654 msec(2) to 436+/-651 msec(2) (P<0.01). Among the fractal HR variability indexes, the power-law slope (ss) (-1.31+/-0.20 versus -1.47+/-0.21, P<0.001) and the short-term fractal exponent a1 (1.16+/-0.19 versus 1.06+/-0.18, P<0.01) decreased significantly. Approximate entropy remained unchanged. CONCLUSIONS: The magnitude of total HR variability and the respiratory vagal modulation of HR do not change over time in the elderly. However, the spectral and fractal characteristics of HR behavior still undergo alterations upon ageing.

Myocardial perfusion reserve and oxidative metabolism contribute to exercise capacity in patients with dilated cardiomyopathy.

BACKGROUND: Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized. METHODS: Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG. RESULTS: Hyperemic perfusion and perfusion reserve were significantly lower in the DCM patients compared with the healthy subjects. There was no difference in left ventricular oxidative metabolism between the 2 groups; however, the patients had a 19% higher right ventricular oxidative metabolism (P=.005). Consequently, the ratio of right to left ventricular oxidative metabolism was also higher (31%) in the patients. There was a strong inverse association between decreased exercise capacity and the ratio of right to left ventricular oxidative metabolism (r=-.68, P<.01) and a positive association with myocardial perfusion reserve (r=.62, P<.01) in the patient group. These 2 parameters along with resting left ventricular work explained 57% of the variability in peak exercise capacity. CONCLUSIONS: Impaired perfusion reserve and an exaggerated imbalance in right to left ventricular oxidative metabolism appear to significantly contribute to the impaired exercise capacity in these DCM patients.

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were measured using oxygen-15-labeled water and positron emission tomography (PET). Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion. FMD was assessed by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/- 0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs 3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD, however, was not different from that of the healthy subjects. Furthermore, neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the patients with IDC, whereas the healthy subjects demonstrated a positive correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus, abnormal myocardial perfusion characterizes patients with IDC. Myocardial perfusion reserve and peripheral endothelial function do not parallel each other in patients with IDC.

Exercise training improves insulin stimulated skeletal muscle glucose uptake independent of changes in perfusion in patients with dilated cardiomyopathy.

OBJECTIVE: The purpose of the present study was to investigate the effects of a 5-month exercise training program on skeletal muscle perfusion and insulin sensitivity at rest and during exercise in patients with idiopathic dilative cardiomyopathy (DCM). BACKGROUND: Patients with chronic heart failure are characterized by impaired insulin sensitivity and endothelial function. It is hypothesized that exercise training improves metabolism by enhancing perfusion in patients with heart failure. METHODS: Fifteen DCM patients (New York Heart Association I-III) on stable medical therapy participated in the study. Patients were divided to receive either supervised strength and aerobic training (n=9, left ventricular ejection fraction [LVEF]=34 +/- 8%) for 5 months (3 times per week at an intensity of 70% of peak oxygen uptake [VO2]) or standard care (n=7, LVEF=36 +/- 6%) based on their living proximity to the exercise training site. Muscle blood flow, oxygen consumption, and glucose uptake were quantified using [15O]-water, [15O]-oxygen, [18F]FDG, and positron emission tomography (PET) during euglycemic hyperinsulinemia and 1-legged isometric exercise. PET studies were performed twice for each patient at the same individual workloads. RESULTS: Exercise training improved exercise capacity by 27% (P<.001). Whole body insulin-stimulated glucose uptake enhanced by 23% (P<.05) and muscle glucose uptake by 53% (P<.05) in the trained group but tended to decrease in the untrained group. When studied using identical workloads, muscle glucose uptake in exercising muscles was enhanced by 55% (P<.05), whereas no changes were observed in muscle blood flow and oxygen uptake. CONCLUSIONS: Exercise training counteracts the impaired insulin sensitivity caused by DCM. Training improves exercise capacity with a concomitant enhancement in whole body, resting, and exercising skeletal muscle glucose uptake. The improved insulin sensitivity is not explained by changes in muscle perfusion suggesting enhanced cellular glucose extraction.