Incidence and remission of type 2 diabetes in relation to degree of obesity at baseline and 2 year weight change: the Swedish Obese Subjects (SOS) study.

AIMS/HYPOTHESIS: The aim of this work was to analyse the rates of incidence and remission of type 2 diabetes in relation to baseline BMI and weight change in the prospective, controlled Swedish Obese Subjects (SOS) study. METHODS: Three-thousand four-hundred and eighty-five obese individuals receiving bariatric surgery or conventional treatment were grouped into four baseline BMI categories (<35, 35-40, 40-45 or ≥ 45 kg/m(2)) and five weight-change categories according to their BMI at 2 years (increase [≥ 1 BMI unit increase], no change [less than 1 BMI unit change], minor reduction [-1 to -9 BMI units], medium reduction [-10 to -14 BMI units] and major reduction [< -15 BMI units]). The incidence and remission of diabetes at 2 years was assessed. RESULTS: Among individuals with no weight change, diabetes incidence rates were 5.5%, 7.4%, 8.3% and 5.2%, in the four baseline BMI categories, respectively. In those with an initial BMI of 35-40, 40-45 and ≥ 45 kg/m(2) who attained a minor reduction in weight, the corresponding rates were 1.3%, 1.2% and 3.4%, respectively. In both the medium- and major-weight-reduction groups, diabetes incidence was ≤ 0.5%. Among individuals with diabetes at baseline, the remission rates were 15.3-26.9% in the no-weight-change groups, and 48.1-70% for individuals who attained a minor weight reduction. In the medium- and major-weight-reduction groups, the remission rate was 77-97%. There were no differences in 2 year incidence and remission rates between different baseline BMI groups that achieved the same degree of weight reduction. CONCLUSIONS/INTERPRETATION: In obese individuals, the favourable effect of weight reduction on type 2 diabetes incidence and remission is independent of initial BMI. Trial registration ClinicalTrials.gov number NCT01479452.

Heart rate variability associates with asymptomatic coronary atherosclerosis.

PURPOSE: Heart rate variability (HRV) becomes impaired in symptomatic coronary artery disease (CAD), particularly, after myocardial infarction. The mechanism how CAD results in impairment of cardiac autonomic regulation is not known. Whether it results rather from coronary atherosclerosis itself than myocardial ischemia and myocardial injury has remained elusive. METHODS: Quantitative coronary angiography was performed in 30 subjects without history of myocardial ischemia, but with high familial risk for CAD. HRV was measured from 24-h ambulatory ECG recordings in time and frequency domain and also non-linear HRV variables SD1 and SD2 in Poincare plot were calculated. Myocardial ischemia was excluded by Tc-99m sestamibi scintigraphy at rest and during exercise. RESULTS: Coronary angiography revealed mean diameter stenosis of 32 ± 19 % in left anterior descending coronary artery, 26 ± 16 % in left circumflex coronary artery and 25 ± 20 % in right coronary artery. An inverse correlation was found between pNN50 and global severity of coronary artery diameter stenosis (r = -0.415, p < 0.05). Correspondingly, power of HF spectral component correlated negatively with global extent of coronary atherosclerosis (r = -0.366, p < 0.05). In Poincare plot, SD1/SD2 ratio correlated with global extent (r = -0.394, p < 0.05) and global burden (r = -0.388, p < 0.05) of coronary arteries. CONCLUSIONS: The severity and extent of coronary atherosclerosis were related to a shift of cardiac autonomic regulation towards sympathetic predominance in asymptomatic subjects without evidence of myocardial ischemia.

Sagittal abdominal diameter as a new predictor for incident diabetes.

OBJECTIVE: Obesity, particularly visceral adiposity, is a major risk factor for type 2 diabetes. The commonly used obesity indicators, BMI, waist girth, and waist-to-hip ratio (WHR), have limited ability to measure the visceral adipose tissue. Sagittal abdominal diameter (SAD) has been shown to predict the amount of visceral fat. So far no study has been published on its ability to predict diabetes occurrence. RESEARCH DESIGN AND METHODS: We assessed and compared the prediction of the four obesity indicators for diabetes incidence in a prospective study based on 5,168 participants from the nationally representative Health 2000 study. RESULTS: During a mean follow-up lasting 8.1 years, 222 incident diabetes cases occurred. In multivariate models adjusted for lifestyle factors, BMI, waist girth, WHR, and SAD were significant predictors of diabetes incidence. The relative risks (95% CI) between high and low levels were 15.0 (6.94-32.6), 11.4 (5.39-23.8), 12.5 (6.47-24.2), and 14.7 (6.89-31.2), respectively. Pairwise interaction analysis showed that the co-occurrence of high BMI and high SAD was associated with the highest diabetes incidence, with a relative risk of 37.0 (11.2-122). After adjustment for waist girth and the components of the metabolic syndrome, the relative risk was 9.88 (2.81-34.7). The corresponding population-attributable fraction estimate was 84% (49-95). CONCLUSIONS: The combination of SAD and BMI measurements yields a new predictor of diabetes incidence.

Baroreflex sensitivity in asymptomatic coronary atherosclerosis.

BACKGROUND: Baroreflex sensitivity (BRS) reflects the effectiveness of cardiac parasympathetic regulation. BRS becomes impaired in stable coronary artery disease (CAD) and after myocardial infarction and carries prognostic information in these patients. Whether impaired BRS is found already in asymptomatic subjects, with subclinical coronary atherosclerosis, has remained elusive. METHODS: The relationship between BRS and coronary atherosclerosis was evaluated in 31 subjects with high familial risk for CAD but without evidence of angina pectoris or myocardial ischaemia. Single photon emission tomography was performed with (99m) Tc-sestamibi to rule out myocardial perfusion defects at rest and during exercise. BRS was assessed by phenylephrine technique. Coronary atherosclerosis was analysed by quantitative coronary angiography (QCA). Percentage of diameter stenosis (PDS) was calculated separately for LAD, LCX, RCA coronary arteries as well as for proximal (PROX), middle (MID) and distal (DIST) coronary artery regions; and for all coronary artery regions (global PDS). RESULTS: Baroreflex sensitivity averaged 7·8 ± 5·4 ms mmHg(-1) . BRS showed inverse correlation to PDS of the proximal coronary artery segments (r = -0·315; P<0·05) and with the most severe single coronary artery stenosis (r = -0·374; P<0·05). Five (16%) subjects had BRS ≤ 3 ms mmHg(-1) . They had more severe PDS of proximal coronary artery segment than subjects with BRS > 3 ms mmHg(-1) (24 ± 7% versus 13 ± 11%, P<0·05, respectively). CONCLUSIONS: Impairment of BRS was found to be associated with the severity of subclinical coronary atherosclerosis in healthy asymptomatic subjects with familial risk of CAD. Asymptomatic subjects with severely blunted BRS may have advanced coronary atherosclerosis.

Intra-individual changes in body weight in population-based cohorts during four decades: the Finnish FINRISK study.

BACKGROUND: The aim of the study was to evaluate trends in intra-individual weight changes over the last four decades in Finland. METHODS: Within the eight FINRISK surveys conducted during the years 1972-2007, we identified individuals who had participated, by chance in at least two surveys. First, individuals aged 25-54 years who had undergone a health examination within 10 years of the first examination (n = 2033) were categorized into five cohorts covering different time periods, and the annual weight change was calculated at follow-up. Second, for each individual aged 25-69 years the longest possible follow-up time (5-35 years) was identified (n = 3443), and the corresponding annual weight change was evaluated. RESULTS: Comparing the five cohorts from different time periods, the annual increase in body weight among men between 25- and 54-year old remained stable in the range of 0.27-0.47 kg per year over the decades, whereas women belonging to the most recent cohorts (the 1990s) gained weight at 0.53-0.63 kg per year, which is more than double the oldest cohort's weight gain of 0.24 kg. Overall, the annual increase in weight was around 0.3 kg in both sexes. The younger participants had a stronger tendency to gain weight than the older, and those with BMI < 25 kg/m(2) gained more than overweight or obese individuals. CONCLUSION: The amount of intra-individual annual increase in body weight among men remained stable over the decades, while it increased among women. The tendency to gain weight was most pronounced among the youngest and among those initially leanest.

Metabolically healthy and unhealthy obesity phenotypes in the general population: the FIN-D2D Survey.

BACKGROUND: The aim of this work was to examine the prevalence of different metabolical phenotypes of obesity, and to analyze, by using different risk scores, how the metabolic syndrome (MetS) definition discriminates between unhealthy and healthy metabolic phenotypes in different obesity classes. METHODS: The Finnish type 2 diabetes (FIN-D2D) survey, a part of the larger implementation study, was carried out in 2007. The present cross-sectional analysis comprises 2,849 individuals aged 45-74 years. The MetS was defined with the new Harmonization definition. Cardiovascular risk was estimated with the Framingham and SCORE risk scores. Diabetes risk was assessed with the FINDRISK score. Non-alcoholic fatty liver disease (NAFLD) was estimated with the NAFLD score. Participants with and without MetS were classified in different weight categories and analysis of regression models were used to test the linear trend between body mass index (BMI) and various characteristics in individuals with and without MetS; and interaction between BMI and MetS. RESULTS: A metabolically healthy but obese phenotype was observed in 9.2% of obese men and in 16.4% of obese women. The MetS-BMI interaction was significant for fasting glucose, 2-hour plasma glucose, fasting plasma insulin and insulin resistance (HOMA-IR)(p < 0.001 for all). The prevalence of total diabetes (detected prior to or during survey) was 37.0% in obese individuals with MetS and 4.3% in obese individuals without MetS (p < 0.001). MetS-BMI interaction was significant (p < 0.001) also for the Framingham 10 year CVD risk score, NAFLD score and estimated liver fat %, indicating greater effect of increasing BMI in participants with MetS compared to participants without MetS. The metabolically healthy but obese individuals had lower 2-hour postload glucose levels (p = 0.0030), lower NAFLD scores (p < 0.001) and lower CVD risk scores (Framingham, p < 0.001; SCORE, p = 0.002) than normal weight individuals with MetS. CONCLUSIONS: Undetected Type 2 diabetes was more prevalent among those with MetS irrespective of the BMI class and increasing BMI had a significantly greater effect on estimates of liver fat and future CVD risk among those with MetS compared with participants without MetS. A healthy obese phenotype was associated with a better metabolic profile than observed in normal weight individuals with MetS.

Body fat measured by a near-infrared interactance device as a predictor of cardiovascular events: the FINRISK'92 cohort.

We evaluated how body fat percentage, measured by a portable near-infrared interactance (NIR) device predicts cardiovascular (CVD), coronary heart disease (CHD), and ischemic stroke events in a prospective population-based survey. The study population consisted of 2,842 men and 3,196 women, who participated in the FINRISK'92 survey. Obesity was assessed with BMI, waist circumference, and waist-to-hip ratio (WHR) and body fat percentage measured with an NIR. Mean length of follow-up was 9 years and 3 months. In Cox proportional hazards regression analyses for men, BMI, waist circumference, and WHR as well as body fat percentage were predictors of a CVD event when adjusted for age and for major risk factors. Hazard ratio (HR) per 1 s.d. was 1.27 (95% confidence interval: 1.10-1.48) for body fat percentage, 1.30 (1.16-1.46) for BMI, and 1.31 (1.16-1.50) for waist circumference. Among women, the body fat lost its predictive power in a fully adjusted model. Body fat percentage, BMI, waist circumference, and WHR were predictors of a CHD event both among men and women, whereas body fat percentage did not predict ischemic stroke among either gender. We observed that body fat percentage measured by an NIR device was a significant predictor of CVD and CHD events among men and women, but in our population-based survey, it did not provide any additional predictive power over and above the simpler measures, such as BMI or WHR.

Seasonal changes in mood and behavior in relation to work conditions among the general population.

OBJECTIVES: This study explored seasonal changes in mood and behavior in relation to work conditions. METHODS: For the 4850 participants, who were 30-64 years of age, had a current profession, and participated in a nationwide population-based study in Finland, data on both the work conditions and seasonal changes in mood and behavior were valid and available for 3623 persons. The participants were divided into groups of indoor and outdoor workers and those working office hours and those not working office hours. RESULTS: There was no difference in the seasonal changes in mood and behavior between the indoor and outdoor workers, except with respect to social activity among the women. The women working indoors reported more extensive seasonal changes in social activity than those working outdoors (P=0.008). There was no difference between the daytime workers and those working nonstandard hours, except that the men working evening and night shifts had more extensive seasonal changes in general (P=0.0001). CONCLUSIONS: Working indoors has a limited effect on seasonal changes in mood and behavior, whereas working evening and night shifts is associated with extensive seasonal changes among men in particular.

Modifiable risk factors have an impact on socio-economic differences in coronary heart disease events.

OBJECTIVES: To investigate the association of socio-economic status, defined by occupational class, income and education, with coronary heart disease (CHD) morbidity and mortality, and further to analyse to which extent modifiable risk factors may explain socio-economic differences in CHD risk. DESIGN: A population-based prospective cohort study including 9,061 men and 10,211 women aged 35-64 at baseline who participated in a cardiovascular risk factor survey in 1982, 1987, 1992 or 1997 in Finland. The subjects were followed for CHD events up till the end of 2001. Cox's proportional hazards model was used in the analysis. RESULTS: Male manual workers had a double risk of CHD death compared with upper-level employees (HR=2.00, 95% CI 1.35-2.97). This excess risk was reduced by 31% when adjusted for traditional cardiovascular risk factors and most of this reduction was due to smoking. CONCLUSIONS: Modifiable risk factors explained about a third of the excess CHD mortality between manual workers and upper-level employees in men. Among women the differences between socio-economic groups were not statistically significant.

C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. A population-based, prospective study.

Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25-64 years was examined in Finland in 1992. The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showed a significant association with CHD risk in men (HR=2.39, 1.08-5.28, comparing fourth quartile to the first quartile). This association remained significant after further adjustment for TNFalpha. TNFalpha also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18-4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFalpha predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP and TNFalpha were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.

The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease.

BACKGROUND AND DESIGN: The recent introduction of sensitive markers of myocardial injury is likely to affect the epidemiology of coronary heart disease (CHD). The American Heart Association together with other societies and research agencies have recently published a new definition on acute CHD to improve consistency in epidemiological and clinical studies (referred here as the '2003 definition'). METHODS: In this study we compare the data on CHD events in the Finnish National Hospital Discharge Register (HDR) and the Causes of Death Register (CDR) with the population-based myocardial infarction (MI) register, FINMONICA/FINAMI. The FINMONICA/FINAMI events were classified according to the 2003 definition. The relevant International Classification of Diseases (ICD) codes from the HDR and CDR were used. RESULTS: Using the 2003 definition as the reference, the overall sensitivity of the ICD codes for MI in the combined HDR and CDR was 83% and the positive predictive value (PPV) was 90%. When the ICD codes for unstable angina were added to the analyses, the sensitivity improved to 85% and the PPV declined to 83%. In the age group 35-74 the sensitivity of the MI codes improved over time, in men from 64% in 1988-1992 to 81% in 1998-2002, and in women from 61 to 78%, respectively. The oldest age group, 75 years or older, had sensitivity and PPV values comparable to those of the younger. CONCLUSION: Diagnoses of fatal and non-fatal CHD events in the Finnish HDR and Causes of Death register were reasonably valid indicators for hard CHD events when compared with the FINMONICA/FINAMI register data.

Hemostatic factors as predictors of stroke and cardiovascular diseases: the FINRISK '92 Hemostasis Study.

We carried out a prospective cohort study to determine whether the plasma levels of fibrinogen, plasminogen, factor VII and lipoprotein (a) are predictors of ischemic stroke and all cardiovascular disease (CVD) events. The FINRISK '92 Hemostasis Study included a random sample of 2372 participants, who were followed-up from winter 1992 to 31 December 2001. During the follow-up, 75 ischemic stroke and 145 coronary events occurred. Of these, 169 were observed among participants free of known CVD at baseline. In this group, fibrinogen and plasminogen were positively associated with the risk of a CVD event with hazard ratios of 1.22 [95% confidence interval (CI), 1.05-1.41] and 1.22 (95% CI, 1.03-1.44), respectively, after adjusting for age, sex and conventional risk factors. Factor VII:C was associated with risk of a future CVD event only among persons with positive history of CVD at baseline (hazard ratio, 1.32; 95% CI, 1.00-1.73). Factor VII antigen was not associated with CVD risk. None of the measured hemostatic factors was a predictor of ischemic stroke events, with the possible exception of lipoprotein (a), which had a borderline significant association (hazard ratio, 1.25; 95% CI, 0.99-1.58). In conclusion, the present study supports the observations that fibrinogen and plasminogen are significant predictors of CVD events, independently of conventional risk factors.

Trends in fatal and nonfatal strokes among persons aged 35 to > or =85 years during 1991-2002 in Finland.

BACKGROUND AND PURPOSE: Declining trends in the incidence and mortality of stroke have been observed in Finland since the beginning of the 1980s until 1997. In this study we analyzed the trends in fatal and nonfatal strokes in Finland during 1991-2002. METHODS: The Finnish Hospital Discharge Register was linked to the National Causes of Death Register to produce a Cardiovascular Disease Register, which includes data on 410 760 cerebrovascular events (International Statistical Classification of Diseases, 10th Revision [ICD-10] codes I60-I69) in patients aged > or =35 years in 1991-2002. RESULTS: Age-standardized incidence of first-ever stroke (ICD-10 codes I60-I64, excluding I63.6) per 100 000 persons declined during 1991-2002 annually by 2.2% (95% CI, -2.4% to -1.9%) among men and 2.5% (-2.8% to -2.2%) among women aged 35 to 74 years. In patients aged 75 to 84 years, the change in the incidence of first-ever stroke was -2.6% per year (-3.0% to -2.2%) among men and -3.2% per year (-3.5% to -2.9%) among women. A similar trend was observed also in the oldest age group, in patients aged > or =85 years. Among patients aged 35 to 74 years, the 28-day case fatality of first-ever stroke declined annually by 3.2% (-3.9% to -2.5%) among men and by 3.0% (-3.8% to -2.2%) among women. A significant decrease was found in the 28-day case fatalities of all subtypes of stroke in this age group. CONCLUSIONS: The favorable development in stroke incidence, mortality, and case-fatality has continued in Finland during 1991-2002.

Trends in fatal and non-fatal coronary heart disease events in Finland during 1991-2001.

OBJECTIVE: To analyse the trends in fatal and non-fatal coronary heart disease (CHD) events in Finland during an 11-year period 1991-2001. DESIGN: Data on hospitalizations due to CHD in the Hospital Discharge Register were linked to the National Causes of Death Register in order to produce a Cardiovascular Disease Register including data on 271,771 events in 234,244 individuals. RESULTS: The annual average decline in the age-standardized CHD mortality rate was 5.2% (95% CI, -5.6, -4.8%) among men and 6.1% (-6.6, -5.6%) among women. The incidence of first myocardial infarction declined annually on average by 5.5% (-5.9, -5.1%) from 1991 to 1997 and by 2.4% (-3.0, -1.7%) from 1998 to 2001 among men. The respective changes among women were -5.9% (-6.5, -5.2%) and -1.7% (-2.7, -0.6%). The number of hospitalizations due to unstable angina pectoris increased between 1991 and 1996 (p = 0.0002) and remained stable for the rest of the study period. CONCLUSIONS: The Cardiovascular Disease Register is a powerful tool for epidemiological monitoring of cardiovascular diseases in Finland.

Cardiac adrenergic innervation is affected in asymptomatic subjects with very early stage of coronary artery disease.

UNLABELLED: The aim of this study was to investigate whether, in subjects with a very early stage of coronary artery disease without hemodynamically significant coronary artery stenoses, cardiac adrenergic innervation is already affected. METHODS: Quantitative coronary angiography and dual-isotope SPECT with 123I-metaiodobenzylguanidine (MIBG) and 99mTc-sestamibi (MIBI) were conducted to assess the function of cardiac adrenergic innervation and myocardial perfusion, respectively, in 30 asymptomatic volunteers with a high familial risk for coronary artery disease. Regional quantitative analysis of MIBG uptake and washout rates was performed using the SPECT data from the anteroseptal, lateral, and inferior myocardial regions, which represented vascular supply by the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA), respectively. RESULTS: The average severity of stenoses was 33% +/- 11% in the LAD, 29% +/- 14% in the LCX, and 26% +/- 19% in the RCA. The severity of stenosis was not related to MIBI uptake in any corresponding myocardial region at rest or during exercise. However, the degree of LAD stenosis correlated directly with delayed MIBG uptake (r = 0.43; P < 0.05) and inversely with MIBG washout (r = -0.34; P = 0.06) of the anteroseptal myocardium. When subjects were divided into tertiles according to the separate severity of stenosis for each coronary artery, delayed MIBG uptake in the anteroseptal region was significantly lower in the lowest LAD tertile (0.34 +/- 0.05) than in the middle (0.41 +/- 0.06; P < 0.01) or highest (0.43 +/- 0.05; P < 0.001) LAD tertile. Correspondingly, delayed MIBG uptake in the lateral region was also lower in the lowest LCX tertile than in the middle tertile (0.34 +/- 0.04 vs. 0.41 +/- 0.06, respectively; P < 0.01). Washout rate was also higher in the lowest LAD tertile (44% +/- 7%) than in the middle (36% +/- 10%; P < 0.05) or highest LAD tertile (34% +/- 8%; P < 0.01). CONCLUSION: The degree of coronary artery stenosis was associated directly with MIBG uptake and inversely with MIBG washout. This finding suggests that the function of cardiac adrenergic nerve endings is modified even in mild coronary artery disease before denervation occurs.