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1.  Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population 
Background
The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.
Methods
The study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7.
Results
In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008).
Conclusion
In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.
doi:10.1186/1471-2261-13-30
PMCID: PMC3663757  PMID: 23594436
Sex hormone binding globulin (SHBG); Testosterone; Gender; Hypertension; BMI
2.  Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden 
Endocrine Connections  2012;2(1):18-22.
Objectives
Obesity is associated with low levels of sex hormone-binding globulin (SHBG). While the reason is not fully understood, we aimed to study the association between serum insulin and levels of SHBG in a random population.
Design and methods
Between 2001 and 2005, a random sample of 2816 participants aged 30–74 years were enrolled in a cross-sectional survey in the South-west of Sweden. Fasting blood samples were collected and an oral glucose tolerance test (OGTT) was conducted in all subjects without known diabetes. Diabetes mellitus was defined according to criteria from WHO, and clinical characteristics were used to discriminate between type 1 (T1D) and type 2 diabetes (T2D). Analyses of SHBG were successful in 2782 participants (98%), who thus constituted the current study population.
Results
We found significant inverse association between levels of SHBG and fasting serum insulin in both genders (men: β=−0.090, P=0.001; women: β=−0.197, P<0.001), which was independent of differences in age and BMI. The associations remained when also differences in fasting plasma glucose were accounted for (men: β=−0.062, P=0.022; women: β=−0.176, P≤0.001). Subjects with T1D exhibited higher levels of SHBG than both T2D (men: δ=15.9 nmol/l, P<0.001; women: δ=71.1 nmol/l, P<0.001) and non-diabetic subjects (men: δ=15.1 nmol/l, P<0.001; women: δ=72.9 nmol/l, P<0.001) independent of age, BMI and fasting glucose levels.
Conclusion
These findings are consistent with high levels of SHBG in T1D, and correspondingly low levels in T2D subjects, suggesting an inhibitory effect of insulin on the SHBG production in the liver.
doi:10.1530/EC-12-0057
PMCID: PMC3680959  PMID: 23781314
sex hormone-binding globulin; insulin; liver; diabetes
3.  Blood Pressure and Global Risk Assessment in a Swedish Population 
This study investigated the association between SCORE and the 2007 ESH-ESC blood pressure categories and explored achievements of blood pressure goals considering global risk. In 2001–2005, a random sample of inhabitants aged 30–74 years in southwestern Sweden was invited to a survey of cardiovascular risk factors. The study enrolled 2816 participants (participation rate 76%). Blood pressure was categorized according to the 2007 ESH-ESC guidelines. Global risk of 10-year CVD death was estimated using the Swedish SCORE chart also accounting for additional risk from diabetes (SCORE-DM). SCORE-DM increased in both sexes from optimal blood pressure to manifest hypertension but did not differ between the normal blood pressure categories. However, SCORE-DM became significantly higher among those with temporarily high blood pressure (men 3.3 SD (1.7), women 1.1 (1.8)) and hypertension (3.6 (2.0), 2.0 (2.0)), compared to optimal blood pressure (1.6 (2.9), 0.6 (1.9)). In the presence of both hypertension and diabetes, high-risk subjects dominated (men 76%, women 61%), and correspondingly a major proportion of patients with known hypertension were at high risk at a blood pressure ≥160/100 mm Hg. These findings have strong implications on blood pressure evaluation in clinical practice and support the use of SCORE to evaluate global risk.
doi:10.1155/2012/835812
PMCID: PMC3443609  PMID: 22991653
4.  Prevalence, awareness, treatment, and control of hypertension: Rule of thirds in the Skaraborg project 
Objective
To describe the prevalence, awareness, and control of hypertension in a Swedish population during the early 2000s to address implications for care and prevention.
Design
A cross-sectional population survey.
Setting
Primary health care in Skaraborg, a rural part of western Sweden.
Subjects
Participants (n =2816) in a population survey of a random sample of men and women between 30 and 75 years of age in the municipalities of Vara (81% participation rate) and Skövde (70%), in western Sweden during 2001–2005.
Main outcome measures
Anthropometric measures, blood pressure, leisure-time physical activity, current smoking, fasting glucose, and cholesterol. Hypertension was defined as ongoing treatment for hypertension, or three consecutive blood pressure readings ≥140 systolic and/or ≥90 mmHg diastolic. Hypertension was considered controlled when the blood pressure was <140/90 mm Hg (both).
Results
The prevalence of hypertension was 20% in both men and women with a steep increase by age. Among hypertensive subjects, 33% were unaware, 36% aware but uncontrolled, and 31% aware and controlled, with no statistically significant differences between men and women. Patients with diabetes had a higher awareness (87% vs. 64%, p <0.001), but the same control rate (56% vs. 44%, p =0.133), when compared with those without diabetes.
Conclusion
A large proportion of subjects with hypertension are still unaware of their condition, or aware but not controlled. It is important to emphasize population-based prevention to reduce the prevalence of hypertension, to perform screening to increase awareness, and to improve implementation of expert guidelines in clinical practice to improve control.
doi:10.3109/02813432.2012.684207
PMCID: PMC3378010  PMID: 22643153
Awareness; control; hypertension; population survey; prevention
5.  High prevalence of type 2 diabetes in Iraqi and Swedish residents in a deprived Swedish neighbourhood - a population based study 
BMC Public Health  2011;11:303.
Background
Immigrants from the Middle-East are at high risk of developing type 2 diabetes (T2D). The aim of the present survey was to measure, in a single deprived neighbourhood, the prevalence rates of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D in residents originating from Iraq and to compare them to those in residents born in Sweden. An additional aim was to identify metabolic, lifestyle and socioeconomic risk factors associated with IFG/IGT and T2D in these residents.
Methods
The study was conducted February 1'st to March 31'st 2010. Men and women aged 45 to 65 years of Swedish or Iraqi origin, living in the neighbourhood of Rosengård, Malmö, Sweden, were randomly selected from the census register. Each participant signed a written informed consent form, underwent a physical examination and an oral glucose tolerance test (OGTT), provided blood samples and filled in a questionnaire. A total of 175 subjects participated (Swedish origin n = 79, Iraqi origin n = 96), reflecting an overall response rate of almost 60%.
Results
In total, 21.9% and 19.0% of the Iraqi and Swedish participants, respectively, suffered from T2D, while 24.0% of the Iraqi participants and 25.3% of the Swedish participants had IFG/IGT. There were no significant differences in prevalence rates relating to country of origin.
Obesity (BMI ≥30 kg/m2) and sedentary leisure time physical activity were highly prevalent in both groups, while a family history of diabetes was more prevalent in participants from Iraq (49.2%) than in those from Sweden (22.8%) (p = 0.001).
Being obese or having a sedentary leisure time were, independently associated with T2D (OR 5.43 (95% CI 2.10-14.02) and 2.89 (95% CI 1.03-8.10) respectively), while economic difficulties were independently associated with IFG/IGT (OR 2.55 (95% CI 1.06-6.15)) after adjustment for the confounding effects of other common risk factors for T2D.
Conclusions
This study reveals a high prevalence of T2D, independently of country of origin (Iraq or Sweden), in a socially vulnerable area and additionally presents a risk factor profile that is markedly different from that of Sweden in general.
doi:10.1186/1471-2458-11-303
PMCID: PMC3120683  PMID: 21569404
6.  Polymorphisms in α- and β-Adrenergic Receptor Genes, Hypertension, and Obstructive Sleep Apnea: The Skaraborg Sleep Study 
The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α2B-, β1-, and β2-adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β1-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02–4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4–21.2).
doi:10.4061/2010/458410
PMCID: PMC2949080  PMID: 20948559
7.  Diastolic dysfunction is associated with sedentary leisure time physical activity and smoking in females only 
Objectives
Left ventricular diastolic dysfunction with preserved systolic function (DD-PSF) is associated with an increased risk of morbidity and mortality. Population-based surveys studying the associations between DD-PSF and lifestyle-associated risk factors, such as leisure time physical activity (LTPA) and smoking, are scarce. Thus, the aims were to explore the associations between DD-PSF and LTPA and smoking, employing optimal echocardiographic techniques.
Design
Cross-sectional study conducted from 2001 to 2003.
Setting
The study was conducted in a random sample of a rural Swedish population.
Subjects
Men and women of 30–75 years of age were consecutively invited for conventional echocardiography and tissue velocity imaging (n = 1149). Structured questionnaires and physical examinations were conducted using standardized methods.
Main outcome measures
DD-PSF was defined according to the European Society of Cardiology criteria excluding subjects with ejection fraction < 45%, or a self-reported history of heart failure.
Results
Complete information was available in 500 men and 538 women. In a multivariate model, DD-PSF was independently associated with sedentary LTPA and smoking in females; sedentary LTPA odds ratio (OR) 2.91, 95% confidence interval (CI) 1.02 to 8.27, and smoking OR 3.42, 95% CI 1.35 to 8.64. The probability of identifying DD-PSF in females with a sedentary LTPA was 37% and increased to 80% if they also had hypertension and were obese.
Conclusions
Sedentary LTPA and smoking are independently associated with DD-PSF in females. Identification of a sedentary lifestyle in females increases the probability of diagnosing DD-PSF.
doi:10.3109/02813432.2010.506803
PMCID: PMC3442333  PMID: 20698731
Echocardiography; gender; family practice; leisure time physical activity; smoking
8.  Salivary cortisol differs with age and sex and shows inverse associations with WHR in Swedish women: a cross-sectional study 
Background
Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.
Methods
In 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.
Results
Morning and Δ-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Δ-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for Δ-cortisol. All findings for Δ-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).
Conclusion
In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Δ-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.
doi:10.1186/1472-6823-9-16
PMCID: PMC2711063  PMID: 19545400
9.  Spatial clustering of mental disorders and associated characteristics of the neighbourhood context in Malmö, Sweden, in 2001 
Study objective
Previous research provides preliminary evidence of spatial variations of mental disorders and associations between neighbourhood social context and mental health. This study expands past literature by (1) using spatial techniques, rather than multilevel models, to compare the spatial distributions of two groups of mental disorders (that is, disorders due to psychoactive substance use, and neurotic, stress related, and somatoform disorders); and (2) investigating the independent impact of contextual deprivation and neighbourhood social disorganisation on mental health, while assessing both the magnitude and the spatial scale of these effects.
Design
Using different spatial techniques, the study investigated mental disorders due to psychoactive substance use, and neurotic disorders.
Participants
All 89 285 persons aged 40–69 years residing in Malmö, Sweden, in 2001, geolocated to their place of residence.
Main results
The spatial scan statistic identified a large cluster of increased prevalence in a similar location for the two mental disorders in the northern part of Malmö. However, hierarchical geostatistical models showed that the two groups of disorders exhibited a different spatial distribution, in terms of both magnitude and spatial scale. Mental disorders due to substance consumption showed larger neighbourhood variations, and varied in space on a larger scale, than neurotic disorders. After adjustment for individual factors, the risk of substance related disorders increased with neighbourhood deprivation and neighbourhood social disorganisation. The risk of neurotic disorders only increased with contextual deprivation. Measuring contextual factors across continuous space, it was found that these associations operated on a local scale.
Conclusions
Taking space into account in the analyses permitted deeper insight into the contextual determinants of mental disorders.
doi:10.1136/jech.2005.040360
PMCID: PMC2563968  PMID: 16614334
mental health; social disorder; socioeconomic environment; spatial analysis
10.  The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men 
Background
The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction.
Methods
The PPARGC1A Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models.
Results
The Ser allele of the PPARGC1A Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03–0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele.
Conclusion
The Ser allele of the PPARGC1A Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.
doi:10.1186/1471-2261-8-37
PMCID: PMC2637232  PMID: 19077249
11.  The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus 
Background
Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp298 allele and T2DM in predisposing to acute myocardial infarction (AMI).
Methods
In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp298 allele versus the risk for AMI.
Results
In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp298 allele was a significant risk factor (HR 3.12 [1.49–6.56], p = 0.003), but not in subjects without diabetes or hypertension.
Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp298 allele (HR 7.20 [3.01–17.20], p < 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men.
Conclusion
We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp298 allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM.
doi:10.1186/1471-2261-8-36
PMCID: PMC2636751  PMID: 19077211
12.  Atheroprotective natural anti-phosphorylcholine antibodies of IgM subclass are decreased in Swedish controls as compared to non-westernized individuals from New Guinea 
Objective
To determine the importance of IgM antibodies against phosphorylcholine (aPC), a novel protective factor for cardiovascular disease (CVD), in a population with a non-western life style as compared with a Swedish control group.
Methods and results
Risk factors for cardiovascular disease were determined in a group of 108 individuals aged 40–86 years from New Guinea and 108 age-and sex-matched individuals from a population based study in Sweden. Antibodies were tested by ELISA. aPC IgM levels were significantly higher among New Guineans than among Swedish controls (p < 0.0001). This difference remained significant among both men and women when controlled for LDL and blood pressure which were lower and smoking which was more prevalent in New Guineans as compared to Swedish controls (p < 0.0001). aPC IgM was significantly and negatively associated with age and systolic blood pressure among Swedish controls and with waist circumference among New Guineans. aPC IgM levels were significantly higher among women than men in both groups. The proportion of the saturated fatty acid (FA) myristic acid in serum cholesterol esters was negatively but polyunsaturated eicosapentaenoic acid and also lipoprotein (a) were positively associated with aPC IgM levels.
Conclusion
IgM-antibodies against PC, which have atheroprotective properties, are higher in a population from Kitava, New Guinea with a traditional lifestyle, than in Swedish Controls, and higher among women than men in both populations tested. Such antibodies could contribute to the low incidence of cardiovascular disease reported from Kitava and could also provide an explanation as to why women have a later onset of CVD than men.
doi:10.1186/1743-7075-4-7
PMCID: PMC1852561  PMID: 17374168
13.  Predictors of acute myocardial infarction mortality in hypertensive patients treated in primary care 
Objective
To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care.
Design
Community-based cohort study.
Setting
Hypertension outpatient clinic in primary health care.
Subjects
Patients who consecutively underwent an annual follow-up during 1992–1993 (n =894; 377 men and 517 women).
Methods
All events of fatal AMI were ascertained by record linkage to the National Mortality Register to December 31, 2002. Gender-specific predictors for AMI mortality were analysed by Cox regression.
Main outcome measure
AMI mortality.
Results
During a mean follow-up of 8.7 years 32 cases (8.5%) of fatal AMI were observed in men and 31 cases (6.0%) were observed in women. Most important predictors for AMI mortality in men were microalbuminuria (HR 3.8, CI 1.8–8.0) and left ventricular hypertrophy (HR 4.0, CI 1.7–9.4), whilst in women type 2 diabetes (HR 4.8, CI 2.4–9.8) was an important predictor. In hypertensive patients without diabetes male gender was associated with high AMI mortality (HR 2.7, CI 1.4–5.3), but in patients with both hypertension and type 2 diabetes the higher risk in men disappeared (HR 0.8, CI 0.4–1.7).
Conclusion
Cardiovascular disease risk factors remain strong predictors of AMI mortality in hypertensive patients but with a different pattern in the two genders. Markers of organ damage are more important predictors in men, whereas markers of impaired glucose metabolism are more important predictors in women.
doi:10.1080/02813430701706253
PMCID: PMC3379766  PMID: 17965983
Acute myocardial infarction; cardiovascular disease risk factors; family practice; hypertension; primary care; type 2 diabetes
14.  Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families – a public health perspective 
BMC Medical Genetics  2006;7:14.
Background
Individuals belonging to the same family share a number of genetic as well as environmental circumstances that may condition a common SBP level. Among the genetic factors, the angiotensin converting enzyme (ACE) gene I/D polymorphism appears as a possible candidate as it might influence both SBP and the pharmacological effect of ACE inhibitors. We aimed to combine genetic epidemiology with public health ideas concerning life-course and multilevel epidemiology in order to understand the role of familial factors regarding individual SBP.
Methods
We applied multilevel regression analysis on 1926 individuals nested within 438 families from South Sweden. Modelling familial SBP variance as a function of age and use of ACE inhibitors we calculates a variance partition coefficient and the proportional change in familial SBP variance attributable to differences in ACE gene I/D polymorphism
Results
Our results suggest the existence of genetic or environmental circumstances that produce a considerable familial clustering of SBP, especially among individuals using ACE-inhibitors. However, ACE gene I/D polymorphism seems to play a minor role in this context. In addition, familial factors – genetic, environmental or their interaction – shape SBP among non-users of ACE inhibitors but their effect is expressed later in the life-course.
Conclusion
Strategies directed to prevent hypertension should be launched in younger rather than in older ages and both prevention of hypertension and its treatment with ACE inhibitors should be focused on families rather than on individuals.
doi:10.1186/1471-2350-7-14
PMCID: PMC1484472  PMID: 16509973
15.  Low adherence with antihypertensives in actual practice: the association with social participation – a multilevel analysis 
BMC Public Health  2005;5:17.
Background
Low adherence is a key factor in explaining impaired effectiveness and efficiency in the pharmacological treatment of hypertension. However, little is known about which factors determine low adherence in actual practice.
The purpose of this study is to examine whether low social participation is associated with low adherence with antihypertensive medication, and if this association is modified by the municipality of residence.
Methods
1288 users of antihypertensive medication were identified from The Health Survey in Scania 2000, Sweden. The outcome was low adherence with antihypertensives during the last two weeks. Multilevel logistic regression with participants at the first level and municipalities at the second level was used for analyses of the data.
Results
Low social participation was associated with low adherence with antihypertensives during the last two weeks (OR = 2.05, 95% CI: 1.05–3.99), independently of low educational level. However, after additional adjustment for poor self-rated health and poor psychological health, the association between low social participation and low adherence with antihypertensives during the last two weeks remained but was not conclusive (OR = 1.80, 95% CI: 0.90–3.61). Furthermore, the association between low social participation and low adherence with antihypertensives during the last two weeks varied among municipalities in Scania (i.e., cross-level interaction).
Conclusion
Low social participation seems to be associated with low adherence with antihypertensives during the last two weeks, and this association may be modified by the municipality of residence. Future studies aimed at investigating health-related behaviours in general and low adherence with medication in particular might benefit if they consider area of residence.
doi:10.1186/1471-2458-5-17
PMCID: PMC551610  PMID: 15720716
16.  Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study 
BMJ : British Medical Journal  1998;316(7133):741-745.
Objective: To investigate possible associations between use of cardiovascular drugs and suicide.
Design: Cross sectional ecological study based on rates of use of eight cardiovascular drug groups by outpatients. A population based cohort study including users of drugs to control hypertension.
Subjects: The ecological study included 152 of Sweden’s 284 municipalities. The cohort study included all inhabitants of one Swedish municipality who during 1988 or 1989 had purchased cardiovascular agents from pharmacies within the municipality. Six hundred and seventeen subjects (18.2%) were classified as users of calcium channel blockers and 2780 (81.8%) as non-users.
Main outcome measures: Partial correlations (least squares method) between rates of use of cardiovascular drugs and age standardised mortality from suicide in Swedish municipalities. Hazard ratios for risk of suicide with adjustments for difference in age and sex in users of calcium channel blockers compared with users of other hypertensive drugs.
Results: Among the Swedish municipalities the use of each cardiovascular drug group except angiotensin converting enzyme inhibitors correlated significantly and positively with suicide rates. After adjustment for the use of other cardiovascular drug groups, as a substitute for the prevalence of cardiovascular morbidity, only the correlation with calcium channel blockers remained significant (r=0.29, P<0.001). In the cohort study, five users and four non-users of calcium channel blockers committed suicide during the follow up until the end of 1994. The absolute risk associated with use of calcium channel blockers was 1.1 suicides per 1000 person years. The relative risk, adjusted for differences in age and sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5).
Conclusions: Use of calcium channel blockers may increase the risk of suicide.
Key messages Clinical trials have a limited ability to detect infrequent adverse effects, so postmarketing reports on adverse effects and observational epidemiological studies are necessary The present investigations, including one cross sectional ecological study and one population based cohort study, suggest an increased risk of suicide in users of calcium channel blockers The results are in accordance with a depressive effect of calcium channel blockers suggested by case reports and a recent epidemiological study Channel blockers should be considered a possible cause of depression and suicide
PMCID: PMC28478  PMID: 9529409

Results 1-17 (17)