Hannu Karanko

Effects on left ventricular hypertrophy of long-term nonpharmacological treatment with sodium restriction in mild-to-moderate essential hypertension.

BACKGROUND Cross-sectional studies on human hypertension have suggested an association between sodium intake and left ventricular hypertrophy (LVH). METHODS AND RESULTS The effects on LVH of a nonpharmacological treatment program based mainly on sodium restriction were examined by serial echocardiography in a 12-month controlled, randomized study that included 76 previously untreated subjects with uncomplicated mild-to-moderate hypertension. The mean daily sodium excretion of 38 subjects randomized into the treatment group decreased from 195 +/- 95 to 94 +/- 73 mmol (P < .001) at 6 months and to 109 +/- 74 mmol (P < .001) at 12 months. This was accompanied by a weight decrease from 81.4 +/- 18.0 to 79.2 +/- 17.4 kg (P < .001) at 6 months and to 80.6 +/- 17.5 kg (NS) at 12 months. The net blood pressure decrease (difference in change from baseline between the treatment and control groups) was 8.9 mm Hg (P < .001) in systolic blood pressure and 6.5 mm Hg (P < .001) in diastolic blood pressure during the first 6 months and 6.7 mm Hg (P < .01) in systolic blood pressure and 3.8 mm Hg (P < .01) in diastolic blood pressure during the last 6 months. After 12 months of sodium restriction, left ventricular mass (LVM) had decreased by 5.4% (from 238 +/- 63 to 225 +/- 51 g, P < .01), and LVM index (LVMI) had decreased by 4.7% (from 123 +/- 26 to 117 +/- 22 g/m2, P < .05), whereas no changes occurred in these parameters in the control group. In treated subjects with baseline LVMI of more than the median value of 133 g/m2 in men and 107 g/m2 in women, LVM decreased by 8.6% (from 272 +/- 62 to 249 +/- 51 g, P < .01), and LVMI decreased by 7.1% (from 140 +/- 23 to 130 +/- 22 g/m2, P < .01). LVM and LVMI remained unchanged in treated subjects with LVMI values equal to or less than the median. CONCLUSIONS Our data suggest that long-term nonpharmacological treatment with moderate sodium restriction decreases LVH.

Multiple Clinic and Home Blood Pressure Measurements Versus Ambulatory Blood Pressure Monitoring

To compare multiple clinic and home blood pressure (BP) measurements and ambulatory BP monitoring in the clinical evaluation of hypertension, we studied 239 middle-aged pharmacologically untreated hypertensive men and women who were referred to the study from the primary healthcare provider. Ambulatory BP monitoring was successfully completed for 233 patients. Clinic BP was measured by a trained nurse with a mercury sphygmomanometer and averaged over 4 duplicate measures. Self-recorded home BP was measured with a semiautomatic oscillometric device twice every morning and twice every evening on 7 consecutive days. Ambulatory BP was recorded with an auscultatory device. Two-dimensionally controlled M-mode echocardiography was successfully performed on 232 patients. Twenty-four-hour urinary albumin was determined by nephelometry. Clinic BP was 144.5+/-12.6/94.5+/-7.4 mm Hg, home BP (the mean of 14 self-recorded measures) was 138.9+/-13.1/92.9+/-8.6 mm Hg, home morning BP (the mean of the first 4 duplicate morning measures) was 137.1+/-13.7/92.4+/-9.2 mm Hg, daytime ambulatory BP was 148.3+/-13. 9/91.9+/-7.8 mm Hg, nighttime ambulatory BP was 125.5+/-16.4/75. 6+/-8.9 mm Hg, and 24-hour ambulatory BP was 141.7+/-14.0/87.2+/-7.6 mm Hg. Pearson correlation coefficients of clinic, home, home morning, and daytime ambulatory BPs to albuminuria and to the characteristics of the left ventricle were nearly equal. In multivariate regression analyses, 36% (P<0.0001) of the cross-sectional variation in left ventricular mass index was attributed to gender and home morning systolic BP in models that originally included age, gender, and clinic, self-measured home morning, and ambulatory daytime, nighttime, and 24-hour systolic and diastolic BPs. We concluded that carefully controlled nonphysician-measured clinic and self-measured home BPs, when averaged over 4 duplicate measurements, are as reliable as ambulatory BP monitoring in the clinical evaluation of untreated hypertension.

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≥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=9.0×10−13). The KCNH2 R176W variant (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.1×10−6). 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.

Common candidate gene variants are associated with QT interval duration in the general population

Objectives.  QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30–40% of the QT‐interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population‐based sample.

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 &khgr;2 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, 1.009–1.040/0.994–1.043), home (hazard ratio, 1.029/1.028; 95% confidence interval, 1.013–1.045/1.005–1.052), and 24-hour ambulatory BP (hazard ratio, 1.033/1.049; 95% confidence interval, 1.019–1.047/1.023–1.077) 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 (&khgr;2=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 (&khgr;2=9.0/12.3, P=0.001/<0.001). Our findings suggest that ambulatory BP is prognostically superior to office and home BP.

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.

Responses of atrial natriuretic factor to long‐term sodium restriction in mild to moderate hypertension

Abstract. The effects of long‐term sodium restriction on plasma atrial natriuretic factor (ANF) concentrations, and the role of baseline plasma ANF concentration as an indicator of changes in haemodynamics and left ventricular hypertrophy during this treatment were studied in 40 middle‐aged previously untreated mildly to moderately hypertensive men and women in a 6‐month controlled randomized study. The main emphasis of the treatment programme was to reduce daily sodium intake to less than 70 mmol. Mean sodium excretion decreased from 148 ± 74 mmol 24 h‐1 to 79 ± 71 mmol 24 h‐1 in the treatment group, but remained unchanged in the control group (173 ± 68 mmol 24 h‐1 vs. 186 ± 62 mmol 24 h‐1; P < 0.01 for the difference in changes between the groups). Mean plasma ANF concentrations in the treatment group were 52.4 ± 20.7 (median 50) pg ml‐1 at baseline and 38.7 ± 26.3 (median 42) pg ml‐1 at 6 months, and the corresponding values in the control group were 55.5 ± 20.5 (median 50) pg ml‐1 and 46.1 ± 32.4 (median 50) pg ml‐1, respectively (P = NS for the difference in changes). The ANF concentration decreased from 70 ± 14 pg ml‐1 to 32 ± 26 pg ml‐1 in treated subjects with a high baseline plasma ANF concentration (> 50 pg ml‐1), but increased from 37 ± 11 pg ml‐1 to 45 ± 27 pg ml‐1 in subjects with a low baseline plasma ANF concentration (< 50 pg ml‐1) (difference in changes P < 0.001). Compared with treated subjects with low baseline plasma ANF levels and with controls, treated subjects with high baseline plasma ANF levels showed a decrease (P < 0.05) in interventricular septal and left posterior wall thicknesses, in relative wall thickness, and in peripheral resistance. These results suggest that in mildly to moderately hypertensive subjects long‐term sodium restriction decreases high plasma ANF concentrations concomitantly with regression of concentric left ventricular hypertrophy, probably as a result of changes in haemodynamics.

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.

Hormone response of diabetic patients to exercise at cool and warm temperatures

SummaryBoth exercise and high ambient temperatures stimulate the secretion of counterregulatory hormones which can change glucose homeostasis. We studied whether in diabetic patients there are any differences in the hormonal response to exercise performed at cool or warm ambient temperatures. A study was performed on eight male insulin-dependent patients at rest and during exercise at + 10° C and + 30° C. Exercise consisted of three consecutive 15-min periods at 60% of maximal aerobic capacity. The concentrations of plasma lactate and counterregulatory hormones at rest were similar at warm and cool temperature, whereas prolactin concentration was higher (P < 0.01) at +30° C. Exercise resulted in an increase in noradrenaline, growth hormone and prolactin (P < 0.01), prevented the diurnal decrease in cortisol, but had no effect on glucagon. Hormone responses to exercise were similar at + 10° C and at +30°C, except for cortisol and noradrenaline which showed greater responses at warm than at cool temperatures. This may have been due to the higher relative work load at warm compared to cool temperatures as suggested by the higher heart rate and greater increase of lactate at +30° C. These data indicate that within a range of ambient temperatures commonly occurring in sports, the response of counterregulatory hormones is largely independent of ambient temperature in insulin-dependent diabetic patients.

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

Abstract 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.