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1.  Correction: The Ghrelin Signalling System Is Involved in the Consumption of Sweets 
PLoS ONE  2014;9(1):10.1371/annotation/69c18638-12de-4f08-9a3c-f8c7bf3a0cc6.
PMCID: PMC3882138
2.  Self-reported leisure time physical activity: a useful assessment tool in everyday health care 
BMC Public Health  2012;12:693.
The individual physical activity level is an independent risk factor for cardiovascular disease and death, as well as a possible target for improving health outcome. However, today´s widely adopted risk score charts, typically do not include the level of physical activity. There is a need for a simple risk assessment tool, which includes a reliable assessment of the level of physical activity. The aim of this study was therefore, to analyse the association between the self-reported levels of physical activity, according to the Saltin-Grimby Physical Activity Level Scale (SGPALS) question, and cardiovascular risk factors, specifically focusing on the group of individuals with the lowest level of self-reported PA.
We used cross sectional data from the Intergene study, a random sample of inhabitants from the western part of Sweden, totalling 3588 (1685 men and 1903 women, mean age 52 and 51). Metabolic measurements, including serum-cholesterol, serum-triglycerides, fasting plasma-glucose, waist circumference, blood pressure and resting heart rate, as well as smoking and self-reported stress were related to the self-reported physical activity level, according to the modernized version of the SGPALS 4-level scale.
There was a strong negative association between the self-reported physical activity level, and smoking, weight, waist circumference, resting heart rate, as well as to the levels of fasting plasma-glucose, serum-triglycerides, low-density lipoproteins (LDL), and self-reported stress and a positive association with the levels of high-density lipoproteins (HDL). The individuals reporting the lowest level of PA (SGPALS, level 1) had the highest odds-ratios (OR) for having pre-defined levels of abnormal risk factors, such as being overweight (men OR 2.19, 95% CI: 1.51-3.19; women OR 2.57, 95 % CI: 1.78-3.73), having an increased waist circumference (men OR 3.76, 95 % CI: 2.61-5.43; women OR 2.91, 95% CI: 1.94-4.35) and for reporting stress (men OR 3.59, 95 % CI: 2.34-5.49; women OR 1.25, 95% CI: 0.79-1.98), compared to the most active individuals, but also showed increased OR for most other risk factors analyzed above.
The self-reported PA-level according to the modernized Saltin-Grimby Physical Activity Level Scale, SGPALS, is associated with the presence of many cardiovascular risk factors, with the most inactive individuals having the highest risk factor profile, including self-reported stress. We propose that the present SGPALS may be used as an additional, simple tool in a routine risk assessment in e.g. primary care, to identify inactive individuals, with a higher risk profile.
PMCID: PMC3519710  PMID: 22920914
3.  Comparison of Apolipoprotein (apoB/apoA-I) and Lipoprotein (Total Cholesterol/HDL) Ratio Determinants. Focus on Obesity, Diet and Alcohol Intake 
PLoS ONE  2012;7(7):e40878.
The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I) has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women) as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.
PMCID: PMC3405058  PMID: 22848405
4.  The "smoker's paradox" in patients with acute coronary syndrome: a systematic review 
BMC Medicine  2011;9:97.
Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival benefit for smokers; that is, the "smoker's paradox". The aim of this study was, therefore, to perform a systematic review of the literature and evidence surrounding the existence of the "smoker's paradox".
Relevant studies published by September 2010 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of Controlled Trials, with a combination of text words and subject headings used. English-language original articles were included if they presented data on hospitalised patients with defined acute coronary syndrome, reported at least in-hospital mortality, had a clear definition of smoking status (including ex-smokers), presented crude and adjusted mortality data with effect estimates, and had a study sample of > 100 smokers and > 100 non-smokers. Two investigators independently reviewed all titles and abstracts in order to identify potentially relevant articles, with any discrepancies resolved by repeated review and discussion.
A total of 978 citations were identified, with 18 citations from 17 studies included thereafter. Six studies (one observational study, three registries and two randomised controlled trials on thrombolytic treatment) observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled patients with acute myocardial infarction (AMI) according to criteria similar to the World Health Organisation criteria from 1979. Among the remaining 11 studies not supporting the existence of the paradox, five studies represented patients undergoing contemporary management.
The "smoker's paradox" was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era, whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox.
PMCID: PMC3179733  PMID: 21861870
5.  Lipid Profile and Its Association with Risk Factors for Coronary Heart Disease in the Highlanders of Lhasa, Tibet 
Sherpa, Lhamo Y., Deji, Hein Stigum, Virasakdi Chongsuvivatwong, Ouzhu Luobu, Dag S. Thelle, Per Nafstad, and Espen Bjertness. Lipid profile and its association with risk factors for coronary heart disease in highlanders of Lhasa, Tibet. High Alt. Med. Biol. 12:57–63, 2011.—The aim of this study was to determine the prevalence of abnormal lipid levels and its association with selected coronary heart disease (CHD) risk factors in the Tibetan population living at 3660 meters above sea level in Lhasa, Tibet. Three hundred seventy one randomly selected male and female, aged 30 to 70 yr took part in the study. Based on the National Cholesterol Education Programme (NCED) adult treatment panel ATP-III 2004 criteria, the age-adjusted prevalence of hypertriglyceridemia was 12.0%; high triglycerides (TG), 33.4%; high low-density lipoprotein cholesterol (LDL-C), 4.8%; and low high-density lipoprotein cholesterol (HDL-C); 24.3%. After adjusting for age, sex, smoking, alcohol, physical activity, diet, hemoglobin (Hb) concentration, and systolic and diastolic blood pressure (BP), an increase in waist-to-hip ratio (WHR) by 0.1 unit was associated with a statistically significant increase in TG, total cholesterol (TC) and LDL-C by 0.25 mmol/L, 0.24 mmol/L, and 0.18 mmol/L, respectively. Female gender increased HDL-C by 0.18 mmol/L when compared with males. Age-adjusted prevalences of Framingham CHD risk score for males and females were 16.3% and 0.6%, respectively. This study demonstrated a high prevalence of hypertriglyceridemia in males, a higher prevalence of low HDL-C in females, and a high hypercholesterolemia prevalence in both genders. However, further longitudinal studies assessing CHD risk factors in high altitude natives are required.
PMCID: PMC3128317  PMID: 21452966
Tibetans; lipid profile; highlanders; heart disease; obesity
6.  The Ghrelin Signalling System Is Involved in the Consumption of Sweets 
PLoS ONE  2011;6(3):e18170.
The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose- intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours.
PMCID: PMC3063250  PMID: 21448464
7.  Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors 
Metabolism  2011;60(1-6):114-120.
The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.
PMCID: PMC3004038  PMID: 20619427
8.  Diagnostic validity of fatal cerebral strokes and coronary deaths in mortality statistics: an autopsy study 
European Journal of Epidemiology  2010;26(3):221-228.
Mortality statistics represent important endpoints in epidemiological studies. The diagnostic validity of cerebral stroke and ischemic heart disease recorded as the underlying cause of death in Norwegian mortality statistics was assessed by using mortality data of participants in the Bergen Clinical Blood Pressure Study in Norway and autopsy records from the Gade Institute in Bergen. In the 41 years of the study (1965–2005) 4,387 subjects had died and 1,140 (26%) had undergone a post mortem examination; 548 (12%) died from cerebral stroke and 1,120 (24%) from ischemic heart disease according to the mortality statistics, compared to 113 (10%) strokes and 323 (28%) coronary events registered in the autopsy records. The sensitivity and positive predictive value of fatal cerebral strokes in the mortality statistics were 0.75, 95% confidence interval (CI) [0.66, 0.83] and 0.86 [0.77, 0.92], respectively, whereas those of coronary deaths were 0.87 [0.84, 0.91] and 0.85 [0.81, 0.89] respectively. Cohen’s Kappa coefficients were 0.78 [0.72, 0.84] for stroke and 0.80 [0.76, 0.84] for coronary deaths. In addition to female gender and increasing age at death, cerebral stroke was a negative predictor of an autopsy being carried out (odds ratio (OR) 0.69, 95% CI [0.54, 0.87]), whereas death from coronary heart disease was not (OR 1.14, 95% CI [0.97, 1,33]), both adjusted for gender and age at death. There was substantial agreement between mortality statistics and autopsy findings for both fatal strokes and coronary deaths. Selection for post mortem examinations was associated with age, gender and cause of death.
PMCID: PMC3079075  PMID: 21170572
Autopsy; Stroke; Ischemic heart disease; Death certification; Validity; Mortality statistics
9.  Obesity in Tibetans Aged 30–70 Living at Different Altitudes under the North and South Faces of Mt. Everest 
Risk factors for chronic diseases in Tibetans may be modified due to hypobaric hypoxia. The objectives of this study were to determine the prevalence of obesity at varying altitudes of 1,200, 2,900 and 3,700 meters above sea-level in Tibet and Nepal; to estimate the effect of altitude on body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). Three cross-sectional studies with simple random sampling were performed on 617 men and women. BMI, WC and WHtR decreased with increasing altitude. It is likely that the physical conditions such as low temperatures and low oxygen levels have a direct catabolic effect.
PMCID: PMC2872340  PMID: 20617052
obesity; WHtR; BMI; waist circumference; Tibetans; Tibet; Everest; Nepal
10.  Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques 
The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques.
The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing.
SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids.
We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
PMCID: PMC1215476  PMID: 16122381
11.  The apolipoprotein E polymorphism and the cholesterol-raising effect of coffee 
The response of serum cholesterol to diet may be affected by the apolipoprotein E (APOE) ε2/ε3/ε4 polymorphism, which also is a significant predictor of variation in the risk of coronary heart disease (CHD) and CHD death. Here, we test the hypothesis that the APOE polymorphism may modulate the cholesterol-raising effect of coffee.
We determined the effect of a coffee abstention period and a daily intake of 600 mL coffee on serum cholesterol and triglycerides with respect to the APOE polymorphism.
121 healthy, non-smoking men (22%) and women (78%) aged 29–65 years, took part in a study with four intervention periods: 1 and 3) a coffee free period of three weeks, 2 and 4) 600 mL coffee/day for four weeks.
APOE ε2 positive individuals had significantly lower total cholesterol concentration at baseline (4.68 mmol/L and 5.28 mmol/L, respectively, p = 0.01), but the cholesterol-raising effect of coffee was not influenced significantly by APOE allele carrier status.
The APOE ε 2 allele is associated with lower serum cholesterol concentration. However, the APOE polymorphism does not seem to influence the cholesterol-raising effect of coffee.
PMCID: PMC539242  PMID: 15571629
controlled study; APOE polymorphism; serum lipids; filtered coffee
12.  The Oslo Health Study: The impact of self-selection in a large, population-based survey 
Research on health equity which mainly utilises population-based surveys, may be hampered by serious selection bias due to a considerable number of invitees declining to participate. Sufficient information from all the non-responders is rarely available to quantify this bias. Predictors of attendance, magnitude and direction of non-response bias in prevalence estimates and association measures, are investigated based on information from all 40 888 invitees to the Oslo Health Study.
The analyses were based on linkage between public registers in Statistics Norway and the Oslo Health Study, a population-based survey conducted in 2000/2001 inviting all citizens aged 30, 40, 45, 59–60 and 75–76 years. Attendance was 46%. Weighted analyses, logistic regression and sensitivity analyses are performed to evaluate possible selection bias.
The response rate was positively associated with age, educational attendance, total income, female gender, married, born in a Western county, living in the outer city residential regions and not receiving disability benefit. However, self-rated health, smoking, BMI and mental health (HCSL) in the attendees differed only slightly from estimated prevalence values in the target population when weighted by the inverse of the probability of attendance.
Observed values differed only moderately provided that the non-attending individuals differed from those attending by no more than 50%. Even though persons receiving disability benefit had lower attendance, the associations between disability and education, residential region and marital status were found to be unbiased. The association between country of birth and disability benefit was somewhat more evident among attendees.
Self-selection according to sociodemographic variables had little impact on prevalence estimates. As indicated by disability benefit, unhealthy persons attended to a lesser degree than healthy individuals, but social inequality in health by different sociodemographic variables seemed unbiased. If anything we would expect an overestimation of the odds ratio of chronic disease among persons born in non-western countries.
PMCID: PMC428581  PMID: 15128460
Epidemiological studies; equity; health surveys; non-response; response bias; self-selection; bias; ethnicity; response rate; disability benefit.

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