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Abstract Background In recent years, several primary care databases recording information from computerized medical records have been established and used for quality assessment of medical care and research. However, to be useful for research purposes, the data generated routinely from every day practice require registration of high quality. In this study we aimed to investigate (i) the frequency and validity of ICD code and drug prescription registration in the new Skaraborg primary care database (SPCD) and (ii) to investigate the sources of variation in this registration. Methods SPCD contains anonymous electronic medical records (ProfDoc III) automatically retrieved from all 24 public health care centres (HCC) in Skaraborg, Sweden. The frequencies of ICD code registration for the selected diagnoses diabetes mellitus, hypertension and chronic cardiovascular disease and the relevant drug prescriptions in the time period between May 2002 and October 2003 were analysed. The validity of data registration in the SPCD was assessed in a random sample of 50 medical records from each HCC (n = 1200 records) using the medical record text as gold standard. The variance of ICD code registration was studied with multi-level logistic regression analysis and expressed as median odds ratio (MOR). Results For diabetes mellitus and hypertension ICD codes were registered in 80-90% of cases, while for congestive heart failure and ischemic heart disease ICD codes were registered more seldom (60-70%). Drug prescription registration was overall high (88%). A correlation between the frequency of ICD coded visits and the sensitivity of the ICD code registration was found for hypertension and congestive heart failure but not for diabetes or ischemic heart disease. The frequency of ICD code registration varied from 42 to 90% between HCCs, and the greatest variation was found at the physician level (MORPHYSICIAN = 4.2 and MORHCC = 2.3). Conclusions Since the frequency of ICD code registration varies between different diagnoses, each diagnosis must be separately validated. Improved frequency and quality of ICD code registration might be achieved by interventions directed towards the physicians where the greatest amount of variation was found.

Aims: Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term treatment adherence, risk factor control, and its association to recurrent ACS and death., Methods and Results: We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio [HR] 1.19 [95% confidence interval (CI) 1.00-1.40]} and death HR [1.26 (95% CI 1.08-1.47)] compared with an LDL-C of 1.8 mmol/L., Conclusion: This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population., Competing Interests: Conflict of interest: S.B. reports research grants from Astra Zeneca and personal fees from Amarin, Amgen, Astra Zeneca, Sanofi, and Novo Nordisk. T.K. report research grants to Karolinska Institutet from Medtronic and ReCor Medical. These companies do not have access to the data and do not have the right to review manuscripts before publication., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Studies in primary healthcare (PHC) assessing the effect of primary prevention with statins on mortality and cardiovascular disease (CVD) are scarce. This study aimed to estimate the effect of statins on all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stroke in individuals in PHC with hypertension without CVD or diabetes., Methods and Results: Using the Swedish PHC quality assurance register QregPV, the study included 13 193 individuals with hypertension without CVD or diabetes, who had filled a first statin prescription between 2010 and 2016, and 13 193 matched controls without a filled statin prescription at the index date. Controls were matched on sex and propensity score using clinical data and data from national registers on comorbidities, prescriptions, and socioeconomic status. The effect of statins was estimated in Cox regression models. During a median of 4.2 years of follow-up, 395 individuals in the statin group vs. 475 in the control group died, 197 vs. 232 died of cardiovascular disease, 171 vs. 191 had an MI, and 161 vs. 181 had a stroke. The treatment effect of statins was significant for all-cause mortality [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.74-0.93] and cardiovascular mortality (HR 0.85, 95% CI 0.72-0.998). Overall, no significant treatment effect of statins was seen for MI (HR 0.89, 95% CI 0.74-1.07), but there was a significant interaction with sex (P = 0.008) with decreased risk of MI for women but not for men (HR 0.66, 95% CI 0.49-0.88 vs. HR 1.09, 95% CI 0.86-1.38)., Conclusion: Primary prevention with statins in PHC was associated with reduced risk of all-cause mortality, cardiovascular mortality, and in women, lower risk of MI., Competing Interests: Conflict of interest: S.F. is an employee of AstraZeneca as of 4 October 2021., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To explore hypertension management in primary healthcare (PHC)., Design: Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021., Setting: Seventy-six PHCCs in eight regions of Sweden., Main Outcome Measures: Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up., Results: The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% ( p  < 0.001) and 61% to 43% ( p  = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in ≥96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300-11300) patients., Conclusions: The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension.

Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities - of both cardiovascular and extracardiac nature - which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment., (© 2023. The Author(s).)

Aims: Childhood obesity is an increasing public health problem. The aim of this study was to investigate the correlation between maternal body mass index in early pregnancy and body mass index in children up to the age of 16 years, and to estimate the prevalence of childhood overweight and obesity in a rural municipality in Sweden., Methods: The study population comprised 312 pregnant women who attended the antenatal clinics in Lidköping during the year 1999 and their 319 children. Data on body mass index from antenatal clinics, child health care centres and school health care were used in linear and multinomial logistic regressions adjusted for maternal age, smoking status, and parity., Results: Overweight or obesity were found in 23.0% of 16-year-olds. The correlation between maternal and child body mass index at all studied ages was positive and significant. Body mass index in 16-year-old boys showed the strongest correlation with maternal body mass index (adjusted r-square = 0.31). The adjusted relative-risk ratio for 16-year old children to be classified as obese as compared to normal weight, per 1 unit increase in maternal body mass index was 1.46 (95% confidence interval 1.29-1.65, p<0.001). Among adolescents with obesity, 37.6% had been overweight or obese at 4 years of age., Conclusions: This study confirms the correlation between maternal and child body mass index and that obesity can be established early in childhood. Further, we showed a high prevalence of overweight and obesity in children, especially in boys, in a Swedish rural municipality. This suggests a need for early intervention in the preventive work of childhood obesity, preferably starting at the antenatal clinic and in child health care centres., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study explored the considerations and experiences of Swedish General Practitioners (GPs) of hypertension treatment in patients 80 years and above., Design: Qualitative design with focus group interviews. Data were analysed by qualitative content analysis., Setting: Primary health care centres (PHCCs), both rural and urban, in the Region of Västra Götaland, Sweden., Subjects: GPs and GP trainees working at PHCCs in 2019 and 2020. Five focus group interviews with 24 physicians were performed., Main Outcome Measures: Considerations and experiences of hypertension treatment in the oldest-old., Results: Eighteen GPs and six GP trainees participated in the study. The latent content was formulated in a theme: 'The physician's decision-making in the treatment of hypertension in the oldest-old implies the inclusion of both medical and humanistic considerations.' The manifest content constituted three main categories: 'The patient characteristics' included medical condition, behavioural factors and daily life. 'The physician's role' described the GP as a professional and her/his experienced support. 'The treatment decision' considered these categories and involved risk-benefit balancing and communication. For the future, the participants proposed better guidelines for the oldest-old multimorbid patients, increased teamwork, continuous cooperation with nurses and better cooperation with hospital physicians., Conclusion: Hypertension care for the oldest-old was experienced as complicated by GPs, due to the need of balancing medical and humanistic considerations. The GP's clinical experience and the received support were of importance when making the treatment decision based on risk-benefit balancing and communication with the patient.Key pointsGPs experienced the task of caring for the oldest-old patients with hypertension as complicated.Patient factors like multimorbidity, polypharmacy, behavioural factors and the patient's condition of daily life were identified.Clinical experience and the experienced support at the PHCC were discussed as important for the GPs' treatment decision.Treatment decisions for the oldest-old patients with hypertension were based on risk-benefit balancing and communication with the patients.

Objective: To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs)., Methods: We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130 mmHg as reference., Results: There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180 mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130 mmHg., Conclusion: In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180 mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130 mmHg. This suggests that lowering SBP to below 145 mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Hypertension and diabetes are common and are both associated with high cardiovascular morbidity and mortality. We aimed to investigate associations between mortality risk and country of birth among hypertensive individuals in primary care with and without concomitant diabetes, which has not been studied previously. In addition, we aimed to study the corresponding risks of myocardial infarction and ischemic stroke., Methods: This observational cohort study of 62 557 individuals with hypertension diagnosed 2001-2008 in the Swedish Primary Care Cardiovascular Database assessed mortality by the Swedish Cause of Death Register, and myocardial infarction and ischemic stroke by the National Patient Register. Cox regression models were used to estimate study outcome hazard ratios by country of birth and time updated diabetes status, with adjustments for multiple confounders., Results: During follow-up time without diabetes using Swedish-born as reference, adjusted mortality hazard ratios per country of birth category were Finland: 1.26 (95% confidence interval 1.15-1.38), high-income European countries: 0.84 (0.74-0.95), low-income European countries: 0.84 (0.71-1.00) and non-European countries: 0.65 (0.56-0.76). The corresponding adjusted mortality hazard ratios during follow-up time with diabetes were high-income European countries: 0.78 (0.63-0.98), low-income European countries: 0.74 (0.57-0.96) and non-European countries: 0.56 (0.44-0.71). During follow-up without diabetes, the corresponding adjusted hazard ratio of myocardial infarction was increased for Finland: 1.16 (1.01-1.34), whereas the results for ischemic stroke were inconclusive., Conclusion: In Sweden, hypertensive immigrants (with the exception for Finnish-born) with and without diabetes have a mortality advantage, as compared to Swedish-born., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Urate lowering therapy (ULT) should, according to recent guidelines, be initiated in the majority of cases already after the first attack of gout. Allopurinol is the first line choice of ULT and should be started with low dose, which is increased until the treatment target is reached. The treatment target should be a blood urate of < 360 µmol/l or < 300 µmol/l (in the presence of topfi), which should be maintained until topfi have resolved. NSAID/cox-inhibitors, colchicine and glucocorticoids are all valid short-term treatments of gout attacks. ULT should not be paused/terminated during attacks and can be initiated during an attack that is adequately treated. Recent RCTs of ULT treatment have demonstrated the importance of thorough and adequate information to the patient and regular follow-up until treatment targets are reached. Such a strategy improve both compliance and outcomes of ULT treatment.

Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.

Hyperuricemia is defined by a blood urate level > 405 µmol/L, the cut-off value at which urate forms crystals in vivo. In 15-20% these individuals develop gout, clinically characterized by attacks of acute arthritis, initially and most commonly affecting MTP 1 or other joints, tendons and soft tissues of the foot. These attacks usually subside within 1 to 2 weeks. Over time attacks occur more frequently and can transform into chronic arthritis characterized by tophi. The gold standard for diagnosis relies on identification of urate crystals by polarization microscopy in aspirated joint fluid. This procedure is rarely performed in primary care where the majority of patients are seen, and gout is usually diagnosed by clinical criteria. New imaging technologies (ultrasound, dual-energy CT) can be helpful when aspiration is not available and when the diagnosis is unclear. Gout has a prevalence of 1.7% and incidence rate of approximately 200 per 100000 person-years in Sweden, figures that increase over time.

Objective: In this study we aimed to estimate the effect of diabetes, educational level and income on the risk of mortality and cardiovascular events in primary care patients with hypertension., Methods: We followed 62,557 individuals with hypertension diagnosed 2001-2008, in the Swedish Primary Care Cardiovascular Database. Study outcomes were death, myocardial infarction, and ischemic stroke, assessed using national registers until 2012. Cox regression models were used to estimate adjusted hazard ratios of outcomes according to diabetes status, educational level, and income., Results: During follow-up, 13,231 individuals died, 9981 were diagnosed with diabetes, 4431 with myocardial infarction, and 4433 with ischemic stroke. Hazard ratios (95% confidence intervals) for diabetes versus no diabetes: mortality 1.57 (1.50-1.65), myocardial infarction 1.24 (1.14-1.34), and ischemic stroke 1.17 (1.07-1.27). Hazard ratios for diabetes and ≤9 years of school versus no diabetes and >12 years of school: mortality 1.56 (1.41-1.73), myocardial infarction 1.36 (1.17-1.59), and ischemic stroke 1.27 (1.08-1.50). Hazard ratios for diabetes and income in the lowest fifth group versus no diabetes and income in the highest fifth group: mortality 3.82 (3.36-4.34), myocardial infarction 2.00 (1.66-2.42), and ischemic stroke 1.91 (1.58-2.31)., Conclusions: Diabetes combined with low income was associated with substantial excess risk of mortality, myocardial infarction and ischemic stroke among primary care patients with hypertension., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study explored the views of primary health care (PHC) physicians on sickness certification after reforms in 2005 prompted by the Swedish government to increase the quality and decrease the inequalities, and costs of sickness certification. Design: Qualitative design with focus group interviews. Data were analysed using qualitative content analysis. Setting: Urban and rural PHC centres in Region Västra Götaland, Sweden. Subjects: GPs, interns, GP trainees and locums working in PHC centres 2015. Six focus group interviews with 28 physicians were performed. Main outcome measures: Experiences and reflections about the sickness certification system. Results: The latent content was formulated in a theme: 'The physicians perceived the sickness certification process as emotive and a challenge to master with differing demands and expectations from authorities, management and patients'. Sickness certification could be easy in clear-cut situations or difficult when other factors besides the pure medical were ruling the decisions. The physicians' coping strategies for the task included both active measures (cooperation with health care staff and social insurance officers) and passive adaptation (giving in or not caring too much) to the circumstances. Proposals for the future were to transfer lengthy sickness certifications and rehabilitation to specialized teams and increase cooperation with rehabilitation coordinators and social insurance officers. Conclusions: Political decisions on laws and regulations for sickness certification impacted the primary health care making the physicians' work difficult and burdensome. Their views and suggestions should be carefully considered in future organization of primary care. KEY POINTS In 2005 Swedish government introduced reforms to decrease the inequalities and costs of sickness certification and facilitate the physicians' work. Focus group interviews with Swedish primary care physicians revealed that sickness certification was challenging due to differing demands from authorities, management and patients.Coping strategies for the sick-listing task included both active measures and passive adaptation to the circumstances.A proposal for future better working conditions for physicians was to transfer lengthy sickness certifications and rehabilitation to specialized teams.

Background: Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management., Methods: In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family., Findings: Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96-1·58) for high-income countries, 1·59 (1·42-1·78) in middle-income countries, and 2·23 (1·79-2·77) in low-income countries (p interaction <0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14-1·98) for high-income countries, 1·80 (1·58-2·06) in middle-income countries, and 2·76 (2·29-3·31) in low-income countries (p interaction <0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (p interaction <0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries., Interpretation: Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education., Funding: Full funding sources are listed at the end of the paper (see Acknowledgments)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes., Methods: The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996-1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation., Results: In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49-3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49-4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06-2.45, p = 0.027, n = 90)., Conclusions: Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The relation between dyslipidemia and atrial fibrillation (AF) development is still controversial. To assess the impact of lipid profile on new-onset AF, we followed 51,020 primary-care hypertensive patients without AF at baseline. After a mean follow-up time of 3.5 years, AF occurred in 2,389 participants (4.7%). We evaluated the association between total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and new-onset AF. In a Poisson regression model fully adjusted for common risk factors of AF, we found that 1.0 mmol/l (39 mg/dl) increase in total cholesterol was associated with 19% lower risk of new-onset AF (95% confidence interval [CI] 9% to 28%), and 1.0 mmol/l (39 mg/dl) increase in low-density lipoprotein cholesterol was associated with 16% lower risk of new-onset AF (95% CI 3% to 27%). Gender-specific Poisson regression analyses revealed that increase in total cholesterol by 1.0 mmol/l (39 mg/dl) was found to be associated with lower risk of new-onset AF with 21% in men (95% CI 8% to 32%), and 18% in women (95% CI 1% to 31%). There was no association between high-density lipoprotein cholesterol or triglycerides and new-onset AF, neither in the whole population with respect to separate gender. In conclusion, in a large hypertensive population we found an inverse association between total cholesterol and new-onset AF for both men and women. Our results confirm previous reports of a dyslipidemia paradox, and extend these observations to the hypertensive population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Our aim was to assess causes of death and temporal changes in excess mortality among patients with new-onset type 2 diabetes in Skaraborg, Sweden., Methods: Patients from the Skaraborg Diabetes Register with prospectively registered new-onset type 2 diabetes 1991-2004 were included. Five individual controls matched for sex, age, geographical area and calendar year of study entry were selected using population records. Causes of deaths until 31 December 2014 were retrieved from the Cause of Death Register. Adjusted excess mortality among patients and temporal changes of excess mortality were calculated using Poisson models. Cumulative incidences of cause-specific mortality were calculated by competing risk regression., Results: During 24 years of follow-up 4364 deaths occurred among 7461 patients in 90,529 person-years (48.2/1000 person-years, 95% CI 46.8-49.7), and 18,541 deaths in 479,428 person-years among 37,271 controls (38.7/1000 person-years, 38.1-39.2). The overall adjusted mortality hazard ratio was 1.47 (p < .0001) among patients diagnosed at study start 1991 and decreased by 2% (p < .0001) per increase in calendar year of diagnosis until 2004. Excess mortality was mainly attributed to endocrine and cardiovascular cause of death with crude subdistributional hazard ratios of 5.06 (p < .001) and 1.22 (p < .001)., Conclusions: Excess mortality for patients with new-onset type 2 diabetes was mainly attributed to deaths related to diabetes and the cardiovascular system, and decreased with increasing year of diagnosis 1991-2004. Possible explanations could be temporal trends of earlier diagnosis due to lowered diagnostic thresholds and intensified diagnostic activities, as well as improved treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To study temporal trends in hypertension treatment and control in Swedish primary care, in relation to clinical characteristics, comorbidity, and drug treatment., Materials and Methods: Repeated cross-sectional analysis of 43 239 hypertensive patients attending primary care in 2001-2002 and of 62 407 patients in 2007-2008., Results: Mean blood pressure (BP) 2007-2008 was 143/79 mmHg in women and 142/81 mmHg in men. Cardiovascular comorbidity and diabetes were present in 13 and 15% of women, and in 18 and 20% of men. Overall BP reductions from 2001-2002 to 2007-2008 were 9.0/3.1 mmHg; greater in women than men, with advancing age, and in patients with comorbidity (all P < 0.001). Attainment of target BP (<140/90 mmHg) increased from 24 and 26% in women and men (2001-2002) to 37 and 37% (2007-2008; all P < 0.001). Most common drug classes in 2001-2002 were, in descending frequency, β blockers, diuretics, and calcium channel blockers (both sexes), and in 2007-2008 β blockers, diuretics, and angiotensin-converting enzyme inhibitors in women, and β blockers, angiotensin-converting enzyme inhibitors, and diuretics in men. The number of drug classes/patient increased from 1.5 (2001-2002) to 1.8 (2007-2008; P < 0.001) but remained low (1.7) in those above target BP., Conclusion: BP control in hypertensive patients attending Swedish primary care has improved over 5-7 years, and more so in high-risk groups. There is, however, room for improvement. In uncontrolled hypertension the combination of several drug classes remain low.

Objective: The objective of this study was to investigate if the research process to evaluate the effect of foot manipulation on pregnancy-related pelvic girdle pain (PPGP) is feasible., Methods: A randomized, single-blind (patients and evaluators) pilot trial was performed to compare foot manipulation to a comparative group at 6-weekly treatment sessions at 5 physiotherapy outpatient clinics in Skaraborg primary care (Skövde, Sweden). Women at 12 to 31 weeks of pregnancy with well-defined PPGP (n = 97) and joint dysfunction or decreased range of movement in the feet were included. Women with a twin pregnancy, low back pain, rheumatoid arthritis, or other serious diseases and those who had previous foot manipulation were excluded. Visual analog scale scores were recorded before study start, before and after each treatment session, and 3 months after delivery., Results: One-hundred and two women were eligible, and 97 were included (group 1: foot manipulation, n = 47; group 2: comparative treatment, n = 50); 40 and 36 in the foot manipulation and comparative treatment groups, respectively, completed the study. The foot manipulation group had a nonsignificant pain relief score compared with that of the comparative group, which had higher pain relief scores. The difference was most pronounced at the first and second treatment sessions. A power analysis showed that at least 250 individuals would be needed in each group to confirm the effect of foot manipulation., Conclusions: This study showed that it is feasible to assess the effect of foot manipulation on PPGP in a multicenter physical therapy outpatient clinic setting. A new larger study should choose a different comparative method and test this hypothesis in a full-scale trial.

Background Atrial fibrillation is associated with increased cardiovascular morbidity and mortality. Hypertension is an important risk factor for the development of atrial fibrillation. Aim This study assessed the relationship between blood pressure control and new-onset atrial fibrillation in hypertensive patients. Methods and results We followed 45,530 hypertensive patients with no previously documented atrial fibrillation, attending primary healthcare in Sweden during 2001-2008. After a mean follow-up of 3.5 years 2057 patients (4.5%) developed atrial fibrillation. Compared to patients with no atrial fibrillation, the new-onset atrial fibrillation group (after adjustment for age, sex, diabetes mellitus, heart failure, ischaemic heart disease, cerebrovascular disease and number of visits) had higher mean in-treatment systolic blood pressure (SBP) and diastolic blood pressure of 3.8 mmHg (95% confidence interval (CI) 3.0-4.6; P < 0.0001) and 1.6 mmHg (95% CI 1.2-2.0; P < 0.0001), respectively. Similarly, mean in-treatment pulse pressure in the new-onset atrial fibrillation group was 2.2 mmHg (95% CI 1.6-2.9; P < 0.001) higher. In a logistic regression analysis, achieved SBP ≥ 140 mmHg was associated with a higher risk of new-onset atrial fibrillation, compared to SBP 130-139 mmHg (odds ratio (OR) 1.5; 95% CI 1.3-1.7) and to SBP < 130 mmHg (OR 1.3; 95% CI 1.1-1.5). There was no difference in risk for new-onset AF between SBP 130-139 and <130 mmHg (OR 0.9; 95% CI 0.7-1.1). Conclusion The present findings indicate that blood pressure control in hypertension is associated with a lower risk of new-onset atrial fibrillation.

Aims: Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or body mass index (BMI) after five years., Methods: Clinical data and blood samples from 460 newly diagnosed type 2 diabetes patients from the Skaraborg diabetes register (SDR) at diagnosis and after 5years and were analyzed with linear and logistic regressions., Results: High BMI at diagnosis and smoking were associated with less reduction of HbA1c i.e. poorer treatment outcome after 5years. A high HbA1c at baseline predicted a greater reduction of HbA1c and need for insulin treatment. High systolic blood pressure and BMI at baseline were associated with greater reduction. The biomarkers were not associated with increase of blood pressure, HbA1c, BMI or need for insulin treatment., Conclusions: Smokers and patients with high HbA1c at diagnosis respond poorer to treatment over 5years. This highlights the importance of advice for non-smoking and weight reduction and more intensive treatment over time., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: A number of registry studies have reported suboptimal adherence to guidelines for cardiovascular prevention during the first year after acute myocardial infarction (AMI). However, only a few studies have addressed long-term secondary prevention after AMI. This study evaluates prevention guideline adherence and outcome of guideline-directed secondary prevention in patients surviving 2 years after AMI., Methods: Patients aged 18-85 years at the time of their index AMI were consecutively identified from hospital discharge records between July 2010 and December 2011 in Gothenburg, Sweden. All patients who agreed to participate in the study (16.2%) were invited for a structured interview, physical examinations and laboratory analysis 2 years after AMI. Guideline-directed secondary preventive goals were defined as optimally controlled blood pressure, serum cholesterol, glucose, regular physical activity, smoking cessation and pharmacological treatment., Results: The mean age of the study cohort (n = 200) at the index AMI was 63.0 ± 9.7 years, 79% were men. Only 3.5% of the cohort achieved all six guideline-directed secondary preventive goals 2 years after infarction. LDL < 1.8 mmol/L was achieved in 18.5% of the cohort, regular exercise in 45.5% and systolic blood pressure <140 mmHg in 57.0%. Anti-platelet therapy was used by 97% of the patients, beta-blockers by 83.0%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers by 76.5% and statins by 88.5%. During follow-up, non-fatal adverse cardiovascular events (cardiac hospitalization, recurrent acute coronary syndrome, angina pectoris, new percutaneous coronary intervention, new onset of atrial fibrillation, post-infarct heart failure, pacemaker implantation, stroke/transient ischemic attack (TIA), cardiac surgery and cardiac arrest) occurred in 47% of the cohort and readmission due to cardiac causes in 30%., Conclusions: Our data showed the failure of secondary prevention in our daily clinical practice and high rate of non-fatal adverse cardiovascular events 2 years after AMI.

Aims: The aims of this study were to determine and evaluate simultaneously the importance of factors known to influence sick-leave certification such as the sick leave-related diagnoses, the patients' socio-economic status, and characteristics of the physicians., Methods: Computerised medical records from 24 public primary health-care centres (PHCC) were used in a multilevel logistic regression analysis at three levels: patients (n=64,354; sex, age, socio-economic status, workplace factors and diagnoses), physicians (n=574; sex and level of experience) and PHCC (n=24). The variation of sick-leave certification at each level was the outcome., Results: Most of the variation was attributed to the patient level and only 3.5% to the physician and 1.2% to the PHCC levels. Among the patient characteristics, psychiatric diagnoses (mostly acute stress) had the highest odds ratio (OR) for sick leave (OR=16.0; 95% confidence interval [CI] 15-17.2), followed by musculoskeletal diagnoses (OR=6.1; 95% CI 5.8-6.5). Other factors with increased OR were low education (OR=1.7; 95% CI 1.6-1.8), use of social allowance (OR=1.4; 95% CI 1.2-1.7) and certain workplaces (manufacture and health and social care). Being older was not associated with increased certified sick leave., Conclusions: The greatest variation in sick-leave certification rate was seen at the patient level, specifically psychiatric diagnoses. Socio-economic factors increasing the risk for sick-leave certification were education, social allowance and occupations in manufacture and caregiving. Understanding the impact of the different factors that influence certified sick leave is important both for targeted interventions in order to facilitate patients' return to work., (© 2015 the Nordic Societies of Public Health.)

Objective: The aim of this study was to examine the reporting of suspected child abuse among Swedish general practitioners (GPs), and to investigate factors influencing them in their decision whether or not to report to child protective services (CPS)., Design: A cross-sectional questionnaire study., Setting: Primary health care centres in western Sweden., Subjects: 177 GPs and GP trainees., Main Outcome Measures: Demographic and educational background, education on child abuse, attitudes to reporting and CPS, previous experience of reporting suspected child abuse, and need of support., Results: Despite mandatory reporting, 20% of all physicians had at some point suspected but not reported child abuse. Main reasons for non-reporting were uncertainty about the suspicion and use of alternative strategies; for instance, referral to other health care providers or follow-up of the family by the treating physician. Only 30% of all physicians trusted CPS's methods of investigating and acting in cases of suspected child abuse, and 44% of all physicians would have wanted access to expert consultation. There were no differences in the failure to report suspected child abuse that could be attributed to GP characteristics. However, GPs educated abroad reported less frequently to CPS than GPs educated in Sweden., Conclusions: This study showed that GPs see a need for support from experts and that the communication and cooperation between GPs and CPS needs to be improved. The low frequency of reporting indicates a need for continued education of GPs and for updated guidelines including practical advice on how to manage child abuse.

Objective: To describe the Swedish Primary Care Cardiovascular Database, SPCCD. Design. Longitudinal data from electronic medical records, linked to national registers. Setting. 48 primary healthcare centres in urban (south-western Stockholm) and rural (Skaraborg) regions in Sweden. Subjects. Patients diagnosed with hypertension 2001-2008., Main Outcome Measures: Blood pressure (BP) and impact of retrieval of data on BP levels, clinical characteristics, co-morbidity and pharmacological treatment., Results: The SPCCD contains 74 751 individuals, 56% women. Completeness of data ranged from > 99% for drug prescriptions to 34% for smoking habits. BP was recorded in 98% of patients during 2001-2008 and in 63% in 2008. Mean BP based on the last recorded value in 2008 was 142 ± 17/80 ± 13 mmHg. Digit preference in BP measurements differed between the two regions, p < 0.001. Antihypertensive drugs were prescribed in primary healthcare to 88% of the patients in 2008; however, when all prescribers were included 96% purchased their drugs. Cardiovascular co-morbidity and diabetes mellitus were present in 28% and 22%, respectively., Conclusion: This large and representative database shows that there is room for improvement of BP control in Sweden. The SPCCD will provide a rich source for further research of hypertension and its complications.

Objective: To follow up patients with elevated calcium concentrations after 10 years., Design: Longitudinal, using medical records, questionnaires, and clinical investigation., Setting: Primary care in Tibro, Sweden, 2008-2010., Subjects: 127 patents with elevated calcium concentrations and 254 patients with normal calcium concentrations from the local community, attending the health care centre., Main Outcome Measures: Diagnoses and mortality in patients with elevated calcium concentrations in 1995-2000, compared with patients with normal calcium concentrations and the background population., Results: The proportion of patients for whom no underlying cause was detected decreased from 55% at baseline to 12% at follow-up. Primary hyperparathyroidism was most common in women, 23% at baseline and 36% at follow-up, and the cancer prevalence increased from 5% to 12% in patients with elevated calcium concentration. Mortality tended to be higher in men with elevated calcium concentrations compared with men with normal calcium concentrations, and was significantly higher than in the background population (SMR 2.3, 95% CI 1.3-3.8). Cancer mortality was significantly increased in men (p = 0.039). Low calcium concentrations were also associated with higher mortality (p = 0.004), compared with patients with normal calcium concentrations., Conclusion: This study underscores the importance of investigating patients with increased calcium concentrations suggesting that most of these patients--88% in our study--will turn out to have an underlying disease associated with hypercalcaemia during a 10-year follow-up period. Elevated calcium concentrations had a different disease pattern in men and women, with men showing increased cancer mortality in this study.

Purpose: To determine factors associated with low persistence in patients initiated on drug treatment for hypertension., Methods: Cohort study using medical records for patients with hypertension in 48 Swedish primary healthcare centres. Data were linked to national registers on dispensed drugs, hospitalizations, outpatient hospital consultations, deaths, migration, and socioeconomy. We identified 5225 patients (55 % women, mean age 61 years) initiated on antihypertensive drug treatment during 2006-2007. Persistence was measured for two years by the dispensed drugs. Patients with a gap of >30 days between end of dispensed supply and the next dispensed prescription were classified as non-persistent. This was calculated by Kaplan-Meier analysis. Cox proportional hazard regression was used to estimate hazard ratios for discontinuation. Potential predictors included age, gender, blood pressure before initiation of therapy, cardiovascular comorbidity, educational level, country of birth, and income., Results: Among patients with a dispensed first prescription, 26 % discontinued treatment during the first year, and a further 9 % discontinued during the second year. Discontinuation (all adjusted) was more common in men (P = 0.002) and in younger patients (30-49 years, P < 0.001). Systolic (P < 0.001) but not diastolic blood pressure was positively associated with persistence. Native-born Swedish citizens and patients born in the other Nordic countries had lower discontinuation rates than those born outside the Nordic countries (P < 0.001)., Conclusion: Major determinants of discontinuation of antihypertensive drug treatment are male sex, young age, mild-to-moderate systolic blood pressure elevation, and birth outside of Sweden.

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

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 α(2B)-, β(1)-, and β(2)-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 β(1)-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).

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.

Krüppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite >99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% CI 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.

Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI)>or=30 events.h-1) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.

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.

The insulin-degrading enzyme is responsible for the intracellular proteolysis of insulin. Its gene IDE is located on chromosome 10, in an area with suggestive linkage to type 2 diabetes and related phenotypes. Due to the impact of genetic variants of this gene in rodents and the function of its protein product, it has been proposed as a candidate gene for type 2 diabetes. Various groups have explored the role of the common genetic variation of IDE on insulin resistance and reported associations of various single nucleotide polymorphisms (SNPs) and haplotypes on both type 2 diabetes and glycemic traits. We sought to characterize the haplotype structure of IDE in detail and replicate the association of common variants with type 2 diabetes, fasting insulin, fasting glucose, and insulin resistance. We assessed linkage disequilibrium, selected single-marker and multimarker tags, and genotyped these markers in several case-control and family-based samples totalling 4,206 Caucasian individuals. We observed no statistically significant evidence of association between single-marker or multimarker tests in IDE and type 2 diabetes. Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians.