Showing papers by "Erik Ingelsson published in 2007"

Clinical utility of different lipid measures for prediction of coronary heart disease in men and women.

Abstract: ContextEvidence is conflicting regarding the performance of apolipoproteins vs traditional lipids for predicting coronary heart disease (CHD) risk.ObjectivesTo compare performance of different lipid measures for CHD prediction using discrimination and calibration characteristics and reclassification of risk categories; to assess incremental utility of apolipoproteins over traditional lipids for CHD prediction.Design, Setting, and ParticipantsPopulation-based, prospective cohort from, Framingham, Massachusetts. We evaluated serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non–HDL-C, apolipoprotein (apo) A-I and apo B, and 3 lipid ratios (total cholesterol:HDL-C, LDL-C:HDL-C, and apo B:apo A-I) in 3322 middle-aged white participants who attended the fourth offspring examination cycle (1987-1991) and were without cardiovascular disease. Fifty-three percent of the participants were women.Main Outcome MeasureIncidence of first CHD event (recognized or unrecognized myocardial infarction, angina pectoris, coronary insufficiency, or coronary heart disease death).ResultsAfter a median follow-up of 15.0 years, 291 participants, 198 of whom were men, developed CHD. In multivariate models adjusting for nonlipid risk factors, the apo B:apo A-I ratio predicted CHD (hazard ratio [HR] per SD increment, 1.39; 95% confidence interval [CI], 1.23-1.58 in men and HR, 1.40; 95% CI, 1.16-1.67 in women), but risk ratios were similar for total cholesterol:HDL-C (HR, 1.39; 95% CI, 1.22-1.58 in men and HR, 1.39; 95% CI, 1.17-1.66 in women) and for LDL-C:HDL-C (HR, 1.35; 95% CI, 1.18-1.54 in men and HR, 1.36; 95% CI 1.14-1.63 in women). In both sexes, models using the apo B:apo A-I ratio demonstrated performance characteristics comparable with but not better than that for other lipid ratios. The apo B:apo A-I ratio did not predict CHD risk in a model containing all components of the Framingham risk score including total cholesterol:HDL-C (P = .12 in men; P = .58 in women).ConclusionsIn this large, population-based cohort, the overall performance of apo B:apo A-I ratio for prediction of CHD was comparable with that of traditional lipid ratios but did not offer incremental utility over total cholesterol:HDL-C. These data do not support measurement of apo B or apo A-I in clinical practice when total cholesterol and HDL-C measurements are available.

Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study.

Abstract: Background— The metabolic syndrome (MetS) is associated with increased cardiovascular risk. We evaluated the relative contributions of circulating biomarkers representing distinct biological pathwa...

Prevalence and Prognostic Impact of Subclinical Cardiovascular Disease in Individuals With the Metabolic Syndrome and Diabetes

Abstract: Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than individuals without MetS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67-2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12-2.33]). Participants with MetS and subclinical disease experienced increased risk of overt CVD (2.67 [1.62-4.41] compared with those without MetS, diabetes, or subclinical disease), whereas the association of MetS with CVD risk was attenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87-2.90]). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition.

Polymorphisms in the SCD1 Gene: Associations With Body Fat Distribution and Insulin Sensitivity

Abstract: Objective: Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans. Research Methods and Procedures: The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis. Results: Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (β) = 1.19, p = 0.007] and waist circumference (β = −4.4, p = 0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference. Conclusion: This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

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

Abstract: 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 stu ...

Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals.

Abstract: Background— The burden and prognostic importance of subclinical cardiovascular disease (CVD) in obesity has not been investigated systematically. Methods and Results— We examined prevalence of subclinical disease in 1938 Framingham Study participants (mean age, 57 years; 59% women) by use of 5 tests (electrocardiography, echocardiography, carotid ultrasound, ankle-brachial pressure, and urinary albumin excretion) and stratified by body mass index (BMI) (normal, <25; overweight, 25 to <30.0; obese, ≥30 kg/m2) and waist circumference (WC) (increased, ≥88 cm for women or ≥102 cm for men). We investigated risk of overt CVD associated with adiposity according to presence versus absence of subclinical disease on any of the 5 tests. Prevalence of subclinical disease was higher in overweight (40.0%; adjusted odds ratio, 1.68) and obese individuals (49.7%; odds ratio, 2.82) compared with individuals with normal BMI (29.3%) and in individuals with increased WC (44.9%; odds ratio, 1.67) compared with normal WC (31.9...

Alcohol intake, insulin resistance, and abdominal obesity in elderly men.

Abstract: RISERUS, ULF AND ERIK INGELSSON. Alcohol intake, insulin resistance, and abdominal obesity in elderly men. Obesity. 2007;15:1766-1773. Objective: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. Research Methods and Procedures: In a population-based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insu- lin secretion (early insulin response), or adiposity (BMI, waist circumference (WC), waist-to-hip ratio). Alcohol in- take was self-reported (questionnaire) and was assessed from a validated 7-day dietary record. The cross-sectional associations were evaluated using multivariable linear re- gression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. Results: In multivariable models, self-estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (- coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p 0.02) and waist-to-hip ratio (0.006 (0.002-0.009), p 0.003). The association with WC and waist-to-hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. Discussion: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers.

Clinical Correlates of Circulating Visfatin Levels in a Community-Based Sample

Abstract: Visfatin, a novel adipokine with insulin-mimetic characteristics, is highly expressed in visceral fat (1). Associations of circulating visfatin concentrations with diabetes and obesity have not been rigorously established, most likely due to small sample sizes of prior studies. Furthermore, relations of visfatin to other cardiovascular risk factors in the general population have not been examined systematically. Accordingly, we tested the hypothesis that plasma visfatin would be positively related to obesity, diabetes, and visceral adiposity in a community-based sample. The design and selection criteria of the Framingham Third Generation Cohort are detailed elsewhere (2). Briefly, 4,095 adults (53% women; mean age 40 years) having at least one parent in the Framingham Offspring Study cohort were recruited in 2001–2005. At their first examination, participants underwent anthropometry, medical history and physical examination, laboratory assessment of cardiovascular risk factors, and, in a subsample, imaging for coronary calcification and adiposity using multidetector computer tomography (MDCT). The present study was performed in a subsample of 374 participants (9% eligible; 53% women) in whom plasma visfatin was assayed. We randomly selected these participants using a weighted sampling scheme with oversampling of the lowest and highest sex-specific quintiles of BMI (ratio of 1.5:2:1.5 for the lowest, middle three, and upper quintiles, respectively) using the participants undergoing MDCT imaging as the sampling frame. We chose this sampling strategy for cost efficiency and optimizing the use of nonrenewable serological resources (given …

Heritability, Linkage, and Genetic Associations of Exercise Treadmill Test Responses

Abstract: Background— The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. Methods and Results— We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritabil...

Sleep disturbances independently predict heart failure in overweight middle-aged men.

Abstract: Background Sleep disturbances are associated with manifest heart failure (HF). However, the relationship between sleep disturbances and incident HF has been less studied. Aims To investigate self-reported sleep disturbances as predictors of HF in a longitudinal, community-based cohort of 2314 middle-aged men. Methods and results Data on self-reported sleep disturbances, as well as established risk factors for HF were collected and analyzed using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF, the presence at baseline of sleep disturbances (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.16–1.99; p=0.002) was an independent risk factor for HF. There was evidence of effect modification between BMI and sleep disturbances. In multivariable-adjusted models, sleep disturbance (HR, 1.58; 95% CI, 1.13–2.21; p=0.008) was an independent risk factor for HF in overweight participants (BMI>25), but not in normal-weight participants (BMI≤25). All results remained similar in a sub-sample excluding all participants suffering from a myocardial infarction during follow-up. Conclusions Self-reported sleep disturbances imply an increased risk of subsequent HF in overweight middle-aged men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction.