Smoking history and all-cause, ischaemic heart disease and lung cancer mortality: follow-up study of 358 551 men and women aged 40-43 years.

AIMS: We studied the health consequences of quitting smoking before age 43 by time since quitting, number of years smoked and cigarettes smoked per day. The outcomes were all-cause, ischaemic heart disease and lung cancer mortality. DESIGN: Prospective study. SETTING: Norwegian counties. PARTICIPANTS: Men and women aged 40-43 years who participated in a national cardiovascular screening programme and who were followed from 1985 to 2018. MEASUREMENTS: Self-reports from questionnaire on time since quitting smoking, years smoked and number of cigarettes per day, and measurements of height, weight and blood pressure, and a blood sample where serum was analysed for total serum cholesterol and triglycerides. FINDINGS: The all-cause mortality rate was 30% higher among quitters less than 1 year ago compared with never smokers (adjusted HR=1.30, 95% CI 1.18-1.43 in men and HR=1.31, 95% CI 1.16 to 1.50 in women). Quitters who had smoked longer than 20 years had 23% higher mortality in men (HR=1.23, 95% CI 1.14 to 1.34) and 32% higher mortality in women (HR=1.32, 95% CI 1.18 to 1.49). Past smoking of more than 20 cigarettes/day was associated with HR=1.14 (1.05-1.23) in men and HR=1.16 (1.01-1.32) in women. The HR for lung cancer was 6.77 (95% CI 4.86 to 9.45) for quitting men who had smoked for more than 20 years compared with never smokers. The corresponding figure for women was 5.75 (95% CI 4.08 to 8.09). CONCLUSIONS: The mortality among quitters was close to that of never smokers, except for a higher mortality for lung cancer, which on the other hand was much lower than the lung cancer mortality in current smokers.

Ten-year mortality among older male recreational endurance athletes in the Birkebeiner Aging Study in comparison with older men from the Tromsø Study.

BACKGROUND: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long-term endurance training is unclear. Thus, we aimed to examine 10-year mortality in older male endurance athletes compared with an older male general population. METHOD: Male athletes (n = 503) participating in an annual long-distance ski race (median years of participation: 14, range: 1-53) from the Norwegian Birkebeiner Aging study (BiAS), and non-athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self-reported leisure-time PA with all-cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. RESULTS: After 10 years (median: 10.4, range: 0.5-11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24-0.49) compared with non-athletes, corresponding to a 15% (95% CI: 12-19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose-response relationship with mortality (p < 0.001). Compared to inactive non-athletes, PA was associated with lower mortality in both active non-athletes and athletes. However, the observed benefit among participants reporting moderate-to-vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14-0.32) than non-athletes (HR: 0.43, 95% CI: 0.31-0.59) (p < 0.01). CONCLUSION: Endurance sport practice was associated with reduced 10-year mortality, beyond the effect of PA in older men. This study suggests that long-term endurance sport practice maintained into older adulthood promotes longevity.

Oral health and cardiovascular disease risk factors and mortality of cerebral haemorrhage, cerebral infarction and unspecified stroke in elderly men: A prospective cohort study.

Background: Stroke mortality comprises different specific diagnoses as cerebral infarction, different haemorrhagic conditions and unspecified stroke. This study seeks to explore the prediction of oral health indicators versus known cardiovascular disease risk factors for stroke mortality. Methods: Altogether, 12,764 men aged 58 to 77 years were invited to the health screening Oslo II in the year 2000. It included general medical measurements and questionnaire information. Mortality data were supplied by Statistics Norway for the 6530 attending men. Cox proportional hazards regression analyses were used to establish prediction models for mortality. Results: Oral health by number of tooth extractions >10 was found to be an independent predictor for cerebral infarction hazard ratio = 2.92, 95% confidence interval (1.24-6.89). This was independent of HDL-Cholesterol (inversely) hazard ratio = 0.21, 95% confidence interval (0.06-0.76), frequent alcohol consumption (drinking 4-7 times per week) hazard ratio = 3.58, 95% confidence interval (1.40-9.13) and diabetes hazard ratio = 4.28, 95% confidence interval (1.68-10.89). Predictors for cerebral haemorrhage were age, hs-C-reactive protein and body mass index (inversely). Age and total cholesterol (inversely) were predictors for unspecified stroke. Conclusions: Oral health measured by number of tooth extractions >10 was an independent predictor for cerebral infarction in addition to age, HDL-C, hs-C-reactive protein and diabetes. The pattern of risk factors varied between the specific stroke diagnoses.

Trends in Modifiable Risk Factors Are Associated With Declining Incidence of Hospitalized and Nonhospitalized Acute Coronary Heart Disease in a Population.

BACKGROUND: Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors. METHODS AND RESULTS: We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48-97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively. CONCLUSIONS: We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events.

Physical activity, resting heart rate, and atrial fibrillation: the Tromsø Study.

AIMS: The objective was to examine the association of physical activity and resting heart rate (RHR) with hospital-diagnosed atrial fibrillation (AF) in a Norwegian cohort. METHODS AND RESULTS: This prospective study included 20 484 adults (50.3% men) who participated in the third Tromsø Study survey in 1986-87. At baseline, physical activity was assessed by a validated questionnaire, and RHR was objectively measured. Participants were followed from baseline through 2010 with respect to incident cases of hospital-diagnosed AF documented on an electrocardiogram. During a mean follow-up period of 20 years (409 045 person-years), 750 participants (70.5% men) were diagnosed with AF. Compared with the low physical activity group, moderately active individuals had a 19% lower risk of any AF [adjusted hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.68-0.97], whereas highly active had similar risk of AF. Vigorously active individuals showed a non-significantly higher risk of AF (adjusted HR 1.37, 95% CI 0.77-2.43). Risk of AF increased with decreasing RHR (adjusted HR 0.92, 95% CI 0.86-0.98 for each 10 b.p.m. increase in RHR), and RHR < 50 b.p.m. was a risk factor for AF (P < 0.05). CONCLUSION: In this prospective cohort study, leisure time physical activity was associated with AF in a J-shaped pattern. Moderate physical activity was associated with a reduced risk of AF, whereas higher activity levels attenuated the benefits of moderate activity. Low RHR was a risk factor for AF. Our results support the hypothesis that moderate and vigorous physical activity may affect AF risk via different pathophysiological mechanisms.

Comparative analysis of antibodies to four major periodontal bacteria in respiratory diseases: a cohort study.

OBJECTIVES: To make a descriptive comparison of antibodies to four major periodontal bacteria and their relation to the respiratory diseases asthma and bronchitis/emphysema, and to cancer incidence. METHODS: The serum of a random sample of men with no history of cancer incidence (n=621) was analysed by the ELISA method for antibody levels of four periodontal bacteria; the anaerobes of the so-called red complex Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD), and the facultative anaerobe Aggregatibacter actinomycetemcomitans (AA). The antibody readings were divided into quartiles and the distribution of cases of the relevant diseases as compared with the non-cases. Comparisons of the quartile distributions were by the Pearson χ2 test. Data and serum from the Oslo II study of Norwegian men from 2000 were used. The ELISA analyses were performed on thawed frozen serum. Cancer data from 17.5 years of follow-up were provided by the Norwegian Cancer Registry. RESULTS: In all, 52 men had reported asthma and 23 men had bronchitis/emphysema at the health screening. Results on cancer incidence are given for all respiratory cancers, n=23, and bronchi and lung cancers separately, n=18. Stratified analyses were performed for the four endpoints showing significant association with low levels of TD antibodies for bronchitis; p=0.035. Both TF and TD were significant for low levels of antibodies among daily smokers; p=0.030 for TF and p<0.001 for TD in the analysis of the full study sample. For PG and AA, no such associations were observed. An association with respiratory cancers was not observed. CONCLUSION: A low level of TD was associated with bronchitis/emphysema compared with the rest of the cohort. In the total study sample, low levels of antibodies to both TF and TD were associated with daily smoking.

Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

BACKGROUND: This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. METHODS AND RESULTS: In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. CONCLUSIONS: Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

Are observational data on therapeutic outcome trustworthy?

Randomized controlled trials have become the golden standard to assess the effectiveness of a therapeutic action. Observational studies can be used to monitor effects of routinely applied therapeutic procedures. The validity of such studies can always be questioned and the results must be assessed in light of possible sources of bias. This issue is exemplified by the analysis of more than 10,000 patients admitted for coronary artery by-pass surgery in Gothenburg early in this century.

Self-reported leisure time physical activity: a useful assessment tool in everyday health care.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Atrial fibrillation, physical activity and endurance training.

INTRODUCTION: Clinical practice and the results of some studies may indicate that physical exercise in the form of endurance training may influence the development of atrial fibrillation (AF). The aim of this paper is to evaluate the scientific background for the hypothesis that there is a connection between physical activity and AF. MATERIAL AND METHOD: This paper is a review article based on searches in PubMed on specific topics, limited to the period 1995 through March 2011. We found 17 original articles and three relatively recent reviews. Each was read by at least two of the authors and then discussed. Seven of the original articles were excluded for methodological reasons, and we therefore discuss the other ten. RESULTS: We found support for the hypothesis that systematic high intensity endurance training such as running can increase the risk of AF, whereas the studies provide no evidence that less intensive physical exercise such as walking increases the risk. Several of the studies have methodological weaknesses. INTERPRETATION: Important questions remain unanswered. There is a need for more studies that can shed light on the connection between training intensity, total volume of intensive endurance training, age-related changes and AF. Studies that include women are also needed.

Alcohol consumption and incidence of pancreatic cancer.

Purpose: The association between alcohol consumption and pancreatic cancer is unsettled. Methods: Altogether 243,169 men and women 20-79 years, without cancer at baseline, were followed with respect to pancreatic cancer by linkage to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. They participated in a cardiovascular survey where information on alcohol consumption, smoking habits, anthropometric measures, and some biological variables were recorded. During 20 years of follow-up, 991 incident pancreatic cancers were registered. We estimated the hazard ratios with the Cox proportional hazards model, and graphed spline curves between glass-units/d of alcohol and hazard ratio of incident pancreatic cancer. Results: The multivariable adjusted hazard per 1 glass-unit/d was 1.08 (95% confidence interval 1.02-1.15) for men and 1.04 (0.97-1.13) for women. The association between alcohol consumption and incident pancreatic cancer was present in ex- and current smokers, but the association could be ascribed to smoking habits. The multivariable adjusted spline curves increased with increasing glass-units/d and with confidence bands not encompassing 1.0 above one glass-unit/day. Conclusion: Our findings of an association between higher level of alcohol consumption and incident pancreatic cancer, could be attributed to confounding by smoking habits.

Low level of antibodies to the oral bacterium Tannerella forsythia predicts bladder cancers and Treponema denticola predicts colon and bladder cancers: A prospective cohort study.

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.

Risk of atrial fibrillation and stroke among older men exposed to prolonged endurance sport practice: a 10-year follow-up. The Birkebeiner Ageing Study and the Tromsø Study.

AIMS: Endurance sport practice is associated with a high prevalence of atrial fibrillation (AF), which increases the risk of stroke in the general population. However, stroke risk in endurance athletes with AF is sparsely investigated. Most studies have been limited by design and are largely restricted to younger and middle-aged populations. Thus, we aimed to investigate AF and stroke risk in older athletes exposed to prolonged endurance training. METHOD: During a 10-year period, 505 male athletes aged ≥65 years frequently participating in a long-distance ski race were compared with 1867 men of the same age from the general population. The main exposure was endurance sport practice with self-reported AF and stroke as outcomes. Stroke risk was further examined by joint modelling of AF and endurance practice. Statistical analysis was conducted with a modified Poisson model. RESULTS: Athletes (median age: 68, range: 65-90) participated in a long-distance ski race over a median of 14 years (range: 1-53). Prevalence (28.5% vs 17.8%) and adjusted risk of AF (risk ratio (RR): 1.88, 95% CI: 1.49 to 2.37) were higher in athletes compared with non-athletes, whereas the prevalence (5.4% vs 9.7%) and risk of stroke were lower (RR: 0.60, 95% CI: 0.37 to 0.95). Compared with athletes without AF, risk of stroke was twofold in athletes (RR: 2.38, 95% CI: 1.08 to 5.24) and nearly fourfold in non-athletes (RR: 3.87, 95% CI: 1.98 to 7.57) with AF. CONCLUSION: Although older male endurance athletes experienced an increased risk of AF, the long-term risk of stroke was substantially reduced compared with non-athletes.

The "smoker's paradox" in patients with acute coronary syndrome: a systematic review.

BACKGROUND: 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". METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diagnostic validity of fatal cerebral strokes and coronary deaths in mortality statistics: an autopsy study.

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.

Increased fraction of exhaled nitric oxide predicts new-onset wheeze in a general population.

RATIONALE: Fraction of exhaled nitric oxide (Fe(NO)) is regarded as a marker of airway inflammation. It is unknown whether increased Fe(NO) in respiratorily healthy subjects increases the risk of developing wheeze. OBJECTIVES: To examine if increased levels of Fe(NO) predicts later onset of wheeze. METHODS: We followed up 2,200 men and women from a general population-based study. At baseline, the subjects were investigated with questionnaires, blood samples, pulmonary function tests, and Fe(NO). At follow-up 4 years later, all subjects were mailed a respiratory questionnaire. The association between incident wheeze and baseline levels of Fe(NO) over the 90th percentile were evaluated calculating hazard ratios using Cox regression models adjusted for smoking habits, age, height, sex, and atopy. MEASUREMENTS AND MAIN RESULTS: The follow-up questionnaire was completed by 1,896 subjects (86.2%). All subjects reporting wheeze, asthma, or asthma symptoms at baseline were excluded resulting in a study population of 1,506 subjects. Of these, 49 subjects reported new-onset wheeze. The median concentration of Fe(NO) at baseline was significantly higher among those with new-onset wheeze (18.8 ppb vs. 15.8 ppb, P = 0.03). In a Cox regression model including all subjects, Fe(NO) over the 90th percentile predicted onset of wheeze (hazard ratio 2.7; 95% confidence interval, 1.4-5.4). In stratified models, this was most apparent among never-smokers and in atopic subjects, for whom the odds ratios were higher. CONCLUSIONS: Our results indicate that increased Fe(NO) is associated with an increased risk of developing wheeze. The results also support the hypothesis that increased level of Fe(NO) among subjects without respiratory symptoms is a sign of subclinical airways inflammation.

Genetic variation of the ghrelin signaling system in females with severe alcohol dependence.

INTRODUCTION: Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). METHODS: Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. RESULTS: We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. CONCLUSION: Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.

Selection bias in a population survey with registry linkage: potential effect on socioeconomic gradient in cardiovascular risk.

Non-participation in population studies is likely to be a source of bias in many types of epidemiologic studies, including those describing social disparities in health. The objective of this paper is to present a non-attendance analysis evaluating the possible impact of selection bias, when investigating the association between education level and cardiovascular risk factors. Data from the INTERGENE research programme including 3,610 randomly selected individuals aged 25-74 (1,908 women and 1,702 men), in West Sweden were used. Only 42% of the invited population participated. Non-attendance analyses were done by comparing data from official registries (Statistics Sweden) covering the entire invited study population. This analysis revealed that participants were more likely to be women, have university education, high income, be married and of Nordic origin compared to non-participants. Among participants, all health behaviours studied were significantly related to education. Physical activity, alcohol use and breakfast consumption were higher in the more educated group, while there were more smokers in the less educated group. Central obesity, obesity and hypertension were also significantly associated with lower education level. Weaker associations were observed for blood lipids, diabetes, high plasma glucose level and perceived stress. The socio-demographic differences between participants and non-participants indicated by the register analysis imply potential biases in epidemiological research. For instance, the positive association between education level and frequent alcohol consumption, may, in part be explained by participation bias. For other risk factors studied, an underestimation of the importance of low socioeconomic status may be more likely.

Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter?

AIM: The aim of this study was to investigate whether the coffee brewing method is associated with any death and cardiovascular mortality, beyond the contribution from major cardiovascular risk factors. METHODS AND RESULTS: Altogether, 508,747 men and women aged 20-79 participating in Norwegian cardiovascular surveys were followed for an average of 20 years with respect to cause-specific death. The number of deaths was 46,341 for any cause, 12,621 for cardiovascular disease (CVD), 6202 for ischemic heart disease (IHD), and 2894 for stroke. The multivariate adjusted hazard ratios (HRs) for any death for men with no coffee consumption as reference were 0.85 (082-0.90) for filtered brew, 0.84 (0.79-0.89) for both brews, and 0.96 (0.91-1.01) for unfiltered brew. For women, the corresponding figures were 0.85 (0.81-0.90), 0.79 (0.73-0.85), and 0.91 (0.86-0.96) for filtered, both brews, and unfiltered brew, respectively. For CVD, the figures were 0.88 (0.81-0.96), 0.93 (0.83-1.04), and 0.97 (0.89-1.07) in men, and 0.80 (0.71-0.89), 0.72 (0.61-0.85), and 0.83 (0.74-0.93) in women. Stratification by age raised the HRs for ages ≥60 years. The HR for CVD between unfiltered brew and no coffee was 1.19 (1.00-1.41) for men and 0.98 (0.82-1.15) for women in this age group. The HRs for CVD and IHD were raised when omitting total cholesterol from the model, and most pronounced in those drinking ≥9 of unfiltered coffee, per day where they were raised by 9% for IHD mortality. CONCLUSION: Unfiltered brew was associated with higher mortality than filtered brew, and filtered brew was associated with lower mortality than no coffee consumption.