The validity of a diagnosis of heart failure in a hospital discharge register

BACKGROUND AND AIMS: The accuracy of a diagnosis of heart failure (HF) in hospital discharge registers is largely unknown. We aimed to determine the validity of such a diagnosis in the Swedish hospital discharge register. METHODS AND RESULTS: In a population-based study of 2322 middle-aged men (the ULSAM study), 321 participants were diagnosed with HF according to the Swedish hospital discharge register, during a median follow-up time of 29 years. A review board examined the validity of the diagnosis according to the European Society of Cardiology definition of HF. Eighty-two percent of the possible cases were classified as having definite HF. An echocardiographic examination increased the validity to 88%. For patients treated at an internal medicine or cardiology clinic the validity was 86% and 91%, respectively. If HF was the primary diagnosis, the validity was 95%, irrespective of clinic type. CONCLUSION: The HF diagnosis in the Swedish hospital discharge register appears slightly less precise than for acute myocardial infarction and stroke. For population-based research, only those with a primary diagnosis of HF in the hospital discharge register should be regarded as definite HF cases, or alternatively the cases should be validated individually.     

Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men.

AIMS: To investigate associations of urinary albumin excretion rate (UAER) and heart failure (HF) incidence in a community-based sample. METHODS AND RESULTS: In a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER (from timed overnight samples) was analysed with established risk factors for HF [acute MI before baseline, acute MI during follow-up (modelled as a time-dependent covariate), hypertension, diabetes, left ventricular hypertrophy, smoking, body mass index, and glomerular filtration rate] and more recently described risk factors [high-sensitive C-reactive protein and insulin sensitivity (clamp glucose disposal rate)] as predictors of HF incidence. Ninety-eight participants developed HF during a median follow-up of 9.0 years. In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in individuals without anti-hypertensive treatment (hazard ratio 1.49; 95% CI 1.13-1.98; P = 0.005). Furthermore, UAER remained an independent predictor of HF, also in participants without diabetes at baseline or myocardial infarction at baseline or during follow-up. There were no significant associations between UAER and HF incidence in individuals with anti-hypertensive treatment. CONCLUSION: Our observations support the notion that low-grade albuminuria is a marker for subclinical cardiovascular damage that predisposes to future HF in the community.     

Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort

OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR.RESEARCH DESIGN AND METHODS—We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C–based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years.RESULTS—Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69–1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m²) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40–0.84]; P < 0.004).CONCLUSIONS—Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.Reduced insulin sensitivity is a key component in the pathogenesis of diabetes, and diabetic nephropathy is a leading cause of end-stage renal disease (ESRD) (1). However, lower insulin sensitivity has also been suggested to be associated with impaired renal function in individuals without overt diabetes (2). For instance, insulin resistance has been shown to predict ESRD in patients with mild renal impairment due to IgA nephritis (3). Furthermore, the opposite chain of events has also been observed; patients with ESRD without diabetes have been shown to develop insulin resistance in the later stage of the disease (3,4). Based on previous data, we hypothesized that reduced insulin sensitivity could be involved in the development of renal dysfunction via pathways that are not primarily mediated via increased glucose levels.We are aware of a few previous community-based studies that have reported the association of reduced insulin sensitivity to diminished renal function (2,5,6). These studies, however, have been limited by the use of surrogate markers of insulin sensitivity or by the use of creatinine-based glomerular filtration rate (GFR). Furthermore, all previous studies have included patients with impaired fasting glucose and impaired glucose tolerance, making it difficult to fully evaluate whether the association between insulin sensitivity and GFR is independent of elevated fasting and postload glucose levels. Moreover, most previous studies (2,5) have included patients with impaired renal function at baseline, and our knowledge of the relationship between insulin sensitivity and GFR within the normal range in the community is limited.Thus, we investigated the association between insulin sensitivity, evaluated by euglycemic clamp, and cystatin C–based GFR in a community-based cohort of elderly men with prespecified subgroup analyses in individuals with normal fasting glucose, normal glucose tolerance, and normal GFR. We also investigated the longitudinal association between insulin sensitivity and renal dysfunction during follow-up and evaluated whether this association was independent of other glucometabolic factors.     

Association study of cholesterol-related genes in Alzheimer’s disease

Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Insulin resistance and risk of congestive heart failure

Context  Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. Objective  To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. Design, Setting, and Participants  The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. Main Outcome Measure  First hospitalization for heart failure. Results  One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. Conclusions  Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.