Matti Mäntysaari

Occurrence, Predictors, and Clinical Significance of Autonomic Neuropathy in NIDDM: Ten-Year Follow-Up From the Diagnosis

Little is known about the occurrence and predictive factors of autonomic neuropathy and its relationship to cardiovascular mortality in NIDDM patients, and no long-term follow-up studies including nondiabetic control subjects are available. A total of 133 patients with newly diagnosed NIDDM (70 men) and 144 control subjects (62 men) were examined at baseline and after 5 and 10 years of follow-up. Deep-breathing tests (baseline, 5-year, and 10-year) and active orthostatic tests (5- and 10-year) were performed. Criteria for autonomic neuropathy were parasympathetic (expiration-to-inspiration ratio ≤1.10), sympathetic (systolic blood pressure decrease ≥30 mmHg in the orthostatic test), and combined autonomic neuropathy (parasympathetic with sympathetic neuropathy). The frequency of parasympathetic neuropathy (NIDDM patients versus control subjects) was 4.9 vs. 2.2% (P = 0.224) at baseline, 19.6 vs. 8.5% (P = 0.017) at 5 years, and 65.0 vs. 28.0% (P < 0.001) at 10 years of follow-up. The frequency of sympathetic neuropathy was 6.8 vs. 5.6% (P = 0.709) at 5 years and 24.4 vs. 9.0% (P = 0.003) at 10 years of follow-up. These figures for combined autonomic neuropathy were 2.1 vs. 1.8% (P = 0.869) at 5 years and 15.2 vs. 4.2% (P = 0.007) at 10 years of follow-up. NIDDM patients with parasympathetic neuropathy at the 10-year examination showed worse glycemic control and higher insulin values than those without parasympathetic neuropathy. Furthermore, in our subjects, women were more prone to have parasympathetic neuropathy than men. Parasympathetic neuropathy at baseline was more frequent in those who died from a cardiovascular cause than those who did not (13 vs. 3%, P = 0.045). Similarly, sympathetic autonomic nervous dysfunction at the 5-year examination predicted the 10-year cardiovascular mortality. In conclusion, the frequency of autonomic neuropathy in NIDDM patients increases sharply with time. The development of autonomic neuropathy is connected with poor glycemic control. Interestingly, a high insulin level seems to have a predictive role in the development of parasympathetic autonomic neuropathy irrespective of obesity and glycemia.

Noninvasive Detection of Cardiac Sympathetic Nervous Dysfunction in Diabetic Patients Using [123I]Metaiodobenzylguanidine

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP- group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P < 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P < 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

Waist circumference and BMI are independently associated with the variation of cardio-respiratory and neuromuscular fitness in young adult men

Objective:To test two hypotheses: (1) cardiorespiratory (CRF) and neuromuscular (NMF) fitness is associated with body mass index (BMI) and waist circumference (WC), independent of each other and of leisure-time physical activity; (2) individuals with high CRF and NMF have lower WC for a given BMI, compared with those with low CRF and NMF.Design:Cross-sectional study.Setting:Men participating in refresher training organized by the Finnish Defence Forces.Participants:A total of 951 men (mean age 29.1, s.d. 4.2 years; BMI 25.3 kg/m2, s.d. 3.8; WC 91, s.d. 11 cm).Main outcome measures:Body mass index, WC, maximal oxygen uptake (VO2max), height of vertical jump, number of push-ups and sit-ups during a 1-min test, static back extension endurance, isometric grip strength, self-reported leisure-time vigorous physical activity. Multiple linear regressions were used to explain the variation in fitness.Results:Waist circumference had significant (P<0.001) negative association with all test results (standardized beta coefficients from −0.23 to −0.77), except for grip strength. Body mass index had significant negative association with VO2max (−0.12; P<0.05), but positive association (P<0.01) with grip strength (0.28), vertical jump (0.21) and push-ups (0.55). For a given BMI, the estimated WC was highest among those with the poorest results for VO2max, vertical jump, sit-ups and push-ups.Conclusions:Despite stronger isometric grip strength, the functional muscle fitness of the upper body, trunk and lower extremities is impaired in individuals with abdominal obesity. Although the known loss of CRF is a serious consequence of obesity, the deterioration of NMF deserves increased attention.

Sympathetic reinnervation after acute myocardial infarction

Myocardial infarction produces sympathetic denervation of the necrotic myocardium and noninfarcted myocardium apical to the injury. Proof of sympathetic reinnervation after myocardial infarction has, however, remained elusive. In this study, we investigated whether cardiac sympathetic reinnervation occurs in men recovering from myocardial infarction. I-123 metaiodobenzylguanidine (MIBG), I-123 paraphenylpentadecanoic acid, and Tc-99m sestamibi scintigraphic imaging were conducted in 13 men 3 and 12 months after a first myocardial infarction to determine the extent of denervated myocardium, the size of the infarct, and the size of the myocardium with reduced perfusion, respectively. A defect was determined as regional uptake of < or = 30% of the maximal myocardial activity. The size of the MIBG defect was not significantly different between 3 and 12 months after infarction (17 +/- 8% and 18 +/- 8% of left ventricular mass, respectively). There was also no significant change in the extent of viable but denervated myocardium at 3 and 12 months (average 9 +/- 6% and 10 +/- 5%, respectively). MIBG activity of the infarct zone (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) did not change (17 +/- 13% and 20 +/- 16%), whereas MIBG activity of the periinfarct zone increased during follow-up (32 +/- 11% and 41 +/- 14%, p < 0.01). This was associated with an increase in periinfarct I-123 paraphenylpentadecanoic acid activity (40 +/- 11% and 48 +/- 9%, p < 0.05), but not Tc-99m sestamibi activity (48 +/- 10% and 48 +/- 11%). In conclusion, we did not observe sympathetic reinnervation in the infarct zone between 3 and 12 months after myocardial infarction. However, MIBG activity of the periinfarct zone increased, suggesting partial reinnervation, and this was associated with a recovery of myocardial metabolic activity of the periinfarct zone.

QT interval and QT dispersion in endurance athletes and in power athletes using large doses of anabolic steroids

We measured electrocardiographic repolarization indexes in athletes. Physiologic adaptive cardiac hypertrophy did not increase QT dispersion in endurance athletes despite long QT intervals due to increased vagal tone. In contrast, power athletes taking large doses of anabolic steroids had increased QT dispersion despite short QT intervals, which seems to reflect altered myocardium in the hypertrophied heart.

Simultaneous invasive and noninvasive evaluations of baroreflex sensitivity with bolus phenylephrine technique

Estimation of baroreflex sensitivity (BRS) is receiving increasing attention in clinical and experimental cardiology. Until recently, in most studies BRS has been assessed on the basis of invasive blood pressure measurement, which limits its use in large-scale studies and in clinical practice. The development of continuous noninvasive blood pressure monitoring has made it possible to assess BRS noninvasively. We compared central invasive and peripheral noninvasive techniques in the assessment of BRS during cardiac catheterization in 40 patients with possible coronary artery disease. The correlation between noninvasive and invasive BRS was high (r = 0.92; p < 0.001). However, the noninvasive method resulted in significantly higher BRS values than did the invasive method (7.1 +/- 6.5 msec/mm Hg vs 5.1 +/- 4.3 msec/mm Hg, respectively; p < 0.001) because of the smaller increase in systolic blood pressure after phenylephrine injection by the noninvasive technique than by the invasive technique (18.9 +/- 6.8 mm Hg vs 25.2 +/- 7.8 mm Hg, respectively; p < 0.01). The difference between noninvasive and invasive BRS correlated positively with invasive BRS (r = 0.54; p < 0.001) and inversely with age (r = -0.39; p < 0.01) and resting systolic blood pressure (r = -0.30, p < 0.05). A noninvasive BRS value of < 4.0 ms/mm Hg showed a sensitivity of 94%, a specificity of 91%, and an accuracy of 93% in identifying cases of reduced invasive BRS (< 3.0 msec/mm Hg). Our findings encourage the use of finger-cuff method in the assessment of BRS. However, noninvasive BRS values were slightly but significantly higher than invasive BRS values, a difference that should be taken into account when BRS is measured by the noninvasive approach.

Autonomic nervous function during whole-body cold exposure before and after cold acclimation.

INTRODUCTION Cold habituation could affect sympatho-vagal balance, which modulates cold stress responses. The study examined cardiovascular autonomic function at the sinus node level during controlled breathing and while undertaking isometric exercise during whole-body cold exposure before and after cold acclimation. METHODS There were 10 male subjects who were exposed to control (25 degrees C) and cold (10 degrees C) environments for 2 h on 10 successive days in a laboratory. Time and frequency domain heart rate variability (HRV) in terms of root mean square of successive differences in RR intervals, total, high, and low frequency power were determined from controlled breathing at the beginning and end of cold acclimation. Heart rate and blood pressure during an isometric handgrip test (30% MVC for 3 min) were recorded at the beginning and end of cold acclimation. Catecholamines (NE and E), mean skin (Tsk), and rectal temperatures (Trect) were measured. RESULTS Acute cold exposure increased total (36%), low (16%), and high frequency power (25%) and RMSSD (34%). Cold acclimation resulted in higher Tsk (0.6 degrees C) and lower NE (24%) response in cold. The cold-induced elevation in high frequency power became significant after cold acclimation, while other HRV parameters remained unchanged. A smaller increase in heart rate and blood pressure occurred at 10 degrees C during the handgrip test after cold acclimation. DISCUSSION Cold exposure increased sympathetic activity, which was blunted after cold acclimation. Parasympathetic activity showed a minor increase in cold, which was enhanced after cold acclimation. In conclusion, cold habituation lowers sympathetic activation and causes a shift toward increased parasympathetic activity.

Sports activity and the use of cigarettes and snus among young males in Finland in 1999-2010

BackgroundStudies of the relationship between sports activity and smoking among adolescents and young adults report contradictory results. We examined the association between sports activity (intensity and type of sport) and the current use of snus (Swedish snuff), cigarette smoking, and the combined use of cigarettes and snus (dual use) among young males in Finland.MethodsData were collected from 16,746 male conscripts who completed a survey during the first days of their conscription during the years 1999-2010 (median age 19 years, response rate 95%). Main outcome measures were self-reported daily/occasional use of snus, cigarette smoking, and dual use. The association between sports activity, type of sport, and several sociodemographic background variables was assessed using logistic regression analysis.ResultsOver the study period (1999-2010), the prevalence of cigarette smoking decreased from 42% to 34%, while snus use increased from 5% to 12%, and dual use increased from 7% to 13% (p < 0.001). Compared with no physical activity, regular competitive sports activity (defined as high-intensity sports activity) was positively associated with use of snus (odds ratio [OR] 10.2; 95% confidence interval [CI]: 7.8-13.5) and negatively with cigarette smoking (OR 0.2; 95% CI: 0.1-0.3). When stratified by type of sport in multivariate models, ice hockey was most strongly associated with snus use (OR 1.6; 95% CI: 1.4-1.9) and dual use (OR 2.0; 95% CI 1.8-2.3) compared with those not playing ice-hockey, followed by other team sports for snus use (OR 1.5; 95% CI: 1.3-1.8) and dual use (OR 1.8; 95% CI: 1.6-2.0) compared with those not participating in other team-sports.ConclusionsOur results show a clear association between snus use and intensity and type of training. Team sports were associated with increased use of snus and dual use compared with no participation in team sports. These findings should be acknowledged when planning and implementing preventive strategies.

Gamified physical activation of young men – a Multidisciplinary Population-Based Randomized Controlled Trial (MOPO study)

BackgroundInactive and unhealthy lifestyles are common among adolescent men. The planned intervention examines the effectiveness of an interactive, gamified activation method, based on tailored health information, peer networks and participation, on physical activity, health and wellbeing in young men. We hypothesize that following the intervention the physical activation group will have an improved physical activity, as well as self-determined and measured health compared with the controls.Methods/designConscription-aged men (18 years) attending compulsory annual call-ups for military service in the city of Oulu in Finland (n = 1500) will be randomized to a 6-months intervention (n = 640) or a control group (n = 640) during the fall 2013. A questionnaire on health, health behaviour, diet and wellbeing is administered in the beginning and end of the intervention. In addition, anthropometric measures (height, weight and waist circumference), body composition, grip strength, heart rate variability and aerobic fitness will be measured. The activation group utilizes an online gamified activation method in combination with communal youth services, objective physical activity measurement, social networking, tailored health information and exercise programs according to baseline activity level and the readiness of changes of each individual. Daily physical activity of the participants is monitored in both the activation and control groups. The activation service rewards improvements in physical activity or reductions in sedentary behaviour. The performance and completion of the military service of the participants will also be followed.DiscussionThe study will provide new information of physical activity, health and health behaviour of young men. Furthermore, a novel model including methods for increasing physical activity among young people is developed and its effects tested through an intervention. This unique gamified service for activating young men can provide a translational model for community use. It can also be utilized as such or tailored to other selected populations or age groups.Trial registrationClinicalTrials.gov Identifier: NCT01376986

Central Aortic Blood Pressure of Hypertensive Men During Short-Term Cold Exposure

BACKGROUND Short- and long-term exposures to cold increase blood pressure and may explain the higher wintertime cardiovascular morbidity and mortality. Hypertensive subjects may be more susceptible to adverse cold-related cardiovascular health effects. The aim of our study was to assess the effect of short-term cold exposure on central aortic blood pressure among untreated hypertensive men. METHODS We conducted a population-based recruitment of 41 hypertensive men and a control group of 20 men without hypertension (aged 55-65 years) who underwent whole-body cold exposure (15-minute exposure to temperature -10 °C, wind 3 m/s, winter clothes). Central aortic blood pressure, augmentation index, and subendocardial viability ratio were measured by radial artery applanation tonometry. RESULTS Short-term cold exposure increased the central aortic blood pressure similarly both in both hypertensive men, from 130/93 to 162/107 mm Hg (P < 0.001) and men in the control group, from 114/81 to 142/91 mmHg (P < 0.001). Augmentation index increased by 12% (from 10% to 22%, P < 0.001; and from 16% to 28%, P < 0.001, respectively), whereas subendocardial viability ratio decreased 10% (from 188% to 177%, P = 0.001; and from 203% to 193%, P = 0.01, respectively) during cold exposure in both hypertensive men and control subjects. CONCLUSIONS Short-term cold exposure increases central aortic blood pressure and cardiac workload, and myocardial oxygen demand slightly increases in relation to blood supply in untreated hypertensive middle-aged men. Because of the higher baseline blood pressure among hypertensive subjects, the cold-induced rise in central aortic blood pressure may increase the risk of adverse cardiovascular health effects.