Sleep deprivation in healthy men has been experimentally found to result in disturbances in glucose metabolism and in sympathovagal imbalance. The aim of the present study was to investigate whether ...sleep disturbances and elevated resting heart rate are associated with increased risk of developing diabetes.
A group of 6,599 initially healthy, nondiabetic men aged 44.5 +/- 4.0 years took part in a prospective, population-based study in Malmö, Sweden. The incidence of diabetes during a mean follow-up of 14.8 +/- 2.4 years was examined in relation to self-reported difficulties in falling asleep and resting heart rate at baseline. Diabetes was assessed at follow-up in all subjects by questionnaire and in a subgroup of 1,551 men by blood glucose measurement.
A total of 615 (9.3%) subjects reported either difficulties in falling asleep or regular use of hypnotics (seen as markers of sleep disturbances), and 158 (2.4%) subjects reported both of these. Altogether, 281 (4.3%) of the men developed diabetes during the follow-up period. Logistic regression models showed difficulties in falling asleep or regular use of hypnotics (odds ratio OR 1.52 95% CI 1.05-2.20) and resting heart rate (OR per 10 bpm 1.13 0.99-1.30) to be associated with development of diabetes when full adjustments were made for baseline age, biological risk factors, lifestyle, family history of diabetes, and social class.
The results suggest that sleep disturbances and, possibly, elevated resting heart rate, in middle-aged men, are associated with an increased risk of diabetes.
Metabolic syndrome (MetS) constitutes a worldwide epidemic burst accounting for billions of cardiovascular disease events and deaths. The genetic basis of MetS is largely unknown. The rs11646213 T → ...A polymorphism maps at 16q23.3 upstream of the CDH13 gene codifying for cadherin-13 (also known as T-cadherin or H-cadherin), which is considered a vascular adiponectin receptor. This and other single-nucleotide polymorphisms have been associated with hypertension and adiponectin level in separate studies. The aim of the present study was to evaluate the effect of the CDH13 rs11646213 T → A polymorphism on individual components of MetS and on MetS. The polymorphism was genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study (n = 4,942) and successively in the Malmö Preventive Project (n = 17,675) cohort at baseline and after an average of 23 years of follow-up (reinvestigation). Four different definitions of MetS were applied to these cohorts. In the cardiovascular arm, CDH13 rs11646213 AA homozygotic women showed a trend toward higher triglycerides and lower high-density lipoprotein cholesterol and presented a higher MetS score (composite sum of MetS phenotypes). MetS (Adult Treatment Panel III definition) was more prevalent in AA homozygotic women compared to T-carriers, a result confirmed in the Malmö Preventive Project cohort at baseline and at reinvestigation with an increased risk from 19% to 45% in AA homozygotic women. In conclusion, the CDH13 rs11646213 T > A polymorphism was consistently associated with MetS in Swedish women recruited in 2 large cohorts. In light of the role of cadherin-13 as a vascular receptor for adiponectin, our study supports the genetic basis for the role of adiponectin in MetS pathogenesis.
Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and ...neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE.
Neutrophil and lymphocyte counts were measured in 27 419 subjects from the general population without a history of CEs, heart failure, or atrial fibrillation. Incidence of CEs was studied in relation to leukocyte counts during a mean follow-up of 13.6 years. Neutrophil but not lymphocyte counts were significantly associated with incidence of CEs. After adjustments for confounding factors, the hazard ratios (95% confidence interval) were 1.00 (reference), 1.07 (0.94-1.23), 1.09 (0.95-1.25), and 1.39 (1.22-1.59) for subjects with neutrophils in the first, second, third, and fourth (highest) sex-specific quartiles, respectively (P for trend <0.001). Of the 1965 subject who had a CE, 471 subjects died on the first day of the CE, in- or outside hospital. The proportions of subjects who died the first day were 19%, 21%, 25%, and 28%, respectively in the first, second, third, and fourth quartiles (P for trend <0.001).
Increased neutrophil counts are associated with incidence of CEs and increased case-fatality rate after a CE.
Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease ...(IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.
Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model.
The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.
Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of ...cardiovascular disease (CVD).
A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline.
Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up.
Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.9, cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors.
C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.
Atrial fibrillation (AF) episodes are thought to be started by an electrical trigger reaching susceptible atria. Such a trigger could be present long before the occurrence of sustained symptomatic ...arrhythmia.
We sought to determine whether supraventricular extrasystoles (SVESs) and supraventricular tachycardias (SVTs) measured at 24-hour Holter electrocardiogram were associated with an increased incidence of AF.
In 1998-2000, 389 individuals (44% men; mean age 65 years) were examined using 24-hour Holter electrocardiogram. Six individuals with known prevalent AF were excluded. After a mean follow-up of 10.3 years, there were 45 cases of incident AF. Hazard ratios (HRs) were computed using multivariable Cox regression adjusting for age, sex, systolic blood pressure, height, weight, smoking, and homeostatic model assessment of insulin resistance.
Frequency of SVESs as well as SVT episodes per hour were independent predictors of incident AF (HR per log unit 1.38; 95% confidence interval 1.14-1.68; P = .001 and HR 1.95; 95% confidence interval 1.21-3.13; P = .006, respectively). Further adjustment for education level, alcohol use, use of medication, and physical activity did not substantially alter the results, nor did analysis using competing risks regression accounting for a competing risk of death. The maximum duration of SVT or the heart rate at SVT was not significantly associated with the incidence of AF.
SVESs and SVTs independently predict AF. The prognostic significance was similar for SVESs, SVTs, and a combination of the two. Repeated efforts to detect AF could be of merit in individuals with frequent supraventricular activity.
Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not ...been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38-50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >/= 3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.
This study explored the relationships between carotid intima-media thickness (IMT), plasma levels of C-reactive protein (CRP), and incidence of heart failure hospitalizations.
Men and women from the ...general population (n=4691), without history of myocardial infarction or stroke, were examined. Incidence of hospitalizations attributable to heart failure was studied over a mean follow-up of 13 years. A total of 75 subjects were hospitalized with a primary diagnosis of heart failure. Adjusted for risk factors, the hazards ratios (95% CI) were 1.00, 0.98 (0.36 to 2.7), 1.9 (0.80 to 4.6), and 2.7 (1.1 to 6.2), respectively, for the 1st, 2nd, 3rd, and 4th quartiles of IMT (P for trend=0.003). The HR associated with CRP levels >or=3 mg/L (versus <1 mg/L) was 2.0 (95% CI: 1.06 to 3.9) after adjustments for risk factors. There was a significant interaction between IMT and CRP on heart failure incidence (P=0.028). Subjects with CRP >or=3 mg/L and IMT in the 4th quartile had an adjusted HR of 3.7 (1.9 to 7.1) compared to those with CRP <3 mg/L and IMT in quartile 1 to 3.
High IMT and high CRP are both independent risk factors for incidence of heart failure requiring hospitalization. The joint exposure to both risk factors substantially increases the risk.
Natriuretic peptides predict poor outcomes in cardiovascular disease. However, the knowledge of their relationship to stroke is limited and prospective studies from the general population are few. ...The purpose of this study was to explore the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) plasma levels and the risk for ischemic stroke and its subtypes.
NT-proBNP and MR-proANP were measured in fasting blood samples from 4,862 subjects (40.2% men, mean age 57.5 ± 6.0 years) without cardiovascular disease from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Incidence of ischemic stroke was monitored over a mean follow-up of 14.9 ± 3.0 years. Stroke cases were etiologically classified according to the TOAST classification. Cox proportional-hazards regression was used to study the incidence of stroke in relationship to NT-proBNP and MR-proANP.
During follow-up, 227 had a first-ever ischemic stroke (large-artery atherosclerosis, n = 35; cardioembolic stroke, n = 44; small-artery occlusion, n = 80; undetermined cause, n = 68). In the age- and sex-adjusted model, only NT-proBNP was associated with total ischemic stroke. This association was completely explained by an increased incidence of cardioembolic stroke. Adjusted for cardiovascular risk factors (age, sex, hypertension, diabetes, smoking, body mass index and low-density lipoprotein cholesterol), the hazard ratios (HRs, 95% confidence interval, 95% CI) for cardioembolic stroke were 1.00 (reference), 1.42 (0.34-6.00), 2.79 (0.77-10.12) and 5.64 (1.66-19.20), respectively, for the 1st, 2nd, 3rd and 4th quartiles of NT-proBNP. The corresponding HRs (95% CIs) for quartiles of MR-proANP were 1.00 (reference), 1.83 (0.55-6.14), 1.20 (0.33-4.34) and 3.96 (1.31-11.99), respectively. In total, 335 (6.9%) subjects were diagnosed with atrial fibrillation during follow-up. Among the cardioembolic stroke cases, 30% were diagnosed with atrial fibrillation before the stroke event and another 36% within 6 months after the stroke. Of the cardioembolic stroke cases with atrial fibrillation, 59% were in the top quartile of NT-proBNP, 69% in the top quartile of MR-proANP and 79% were either in the top quartile of NT-proBNP or in the top quartile of MR-proANP.
High plasma levels of NT-proBNP and MR-proANP are associated with a substantially increased risk of cardioembolic stroke, but not with other subtypes of ischemic stroke. The results suggest that assessment of stroke risk, including electrocardiography, is warranted in subjects with high NT-proBNP or MR-proANP.
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