The objective of this study was to study the association between antithrombotic treatment and risk of hemorrhagic stroke (HS) in patients with atrial fibrillation (AF) treated in primary health care.
Study population included all adults (n = 12,215) 45 years and older diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Outcome was defined as a first hospital episode with a discharge episode of HS after the AF diagnosis. Association between HS and persistent treatment with antithrombotic agents (warfarin, acetylsalicylic acid (ASA), clopidogrel) was explored using Cox regression analysis, with hazard ratios (HRs) and 95 % CIs. Adjustment was made for age, socioeconomic status, and co-morbid cardiovascular conditions.
During a mean of 5.8 years (SD 2.4) of follow-up, 162 patients (1.3 %; 67 women and 95 men) with HS were recorded. The adjusted risk associated with persistent warfarin treatment compared to no antithrombotic treatment consistently showed no increased HS risk, HR for women 0.53 (95 % CI 0.23-1.27) and for men 0.55 (95 % CI 0.29-1.04); corresponding HRs for ASA were, for women, 0.45 (95 % CI 0.14-1.44) and, for men, 0.56 (95 % CI 0.24-1.29).
In this clinical setting, we found no evidence pointing to an increased risk of HS with antithrombotic treatment.
Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women.
Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533?MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors.
Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95% CI 1.03-1.37, p?=?.02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men.
In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.
The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) >40% and with pre-specified sub-group analyses in individuals with a GFR >60 mL/min/m(2).
Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography.
In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR >60 mL/min/m(2).
Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.
Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD).
We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H2 blockers (H2B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure.
Users of PPIs, compared with users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76-7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use.
Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.
Congestive heart failure (CHF) is a serious complication in patients with atrial fibrillation (AF).
To study associations between relevant co-morbidities and CHF in patients with AF.
Study population included all adults (n=12,283) =45 years diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Logistic regression was used to calculate odds ratios with 95% confidence intervals (CIs) for the associations between co-morbidities, and prevalent CHF. In a subsample (n=9424), (excluding patients with earlier CHF), Cox regression was used to estimate hazard ratios with 95% CIs for the association between co-morbidities, and a first hospital diagnosis of CHF, after adjustment for age and socio-economic factors.
During 5.4 years' follow-up (standard deviation 2.5), 2259 patients (24.0%; 1135 men, 21.8%, and 1124 women, 26.7%) were diagnosed with CHF. Patients with hypertension were less likely to have CHF, while a diagnosis of coronary heart disease, valvular heart disease, diabetes, or chronic obstructive pulmonary disease (COPD), was consistently associated with CHF among men and women. CHF was more common among women with depression. The relative fully adjusted risk of incident CHF was increased for the following diseases in men with AF: valvular heart disease, cardiomyopathy, and diabetes; and for the following diseases in women: valvular heart disease, diabetes, obesity, and COPD. The corresponding risk was decreased among women for hypertension.
In this clinical setting we found hypertension to be associated with a decreased risk of CHF among women; valvular heart disease and diabetes to be associated with an increased risk of CHF in both sexes; and cardiomyopathy to be associated with an increased risk of CHF among men.
Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.
Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.
Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.
An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.
Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking.
To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.
Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.
During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).
Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.
The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.
To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.
We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11?311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.
Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; a-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.
Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.
Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P?=?.27). Linoleic acid was inversely associated with all-cause mortality (HR,?0.90; 95% CI, 0.82-0.98; P?=?.02) and directly associated with intake (P?
To study association between relevant cardiovascular pharmacotherapy and incident congestive heart failure (CHF) in patients with atrial fibrillation treated in primary health care.
Study population included all adults (n?=?7975) aged 45 years and older diagnosed with atrial fibrillation at 75 primary care centers in Sweden between 2001 and 2007. Outcome was defined as a first diagnosis of CHF post-atrial fibrillation diagnosis. Association between CHF and treatment with relevant cardiovascular pharmacotherapies (beta blockers, calcium blockers, digitalis, diuretics, RAS blockers, and statins) was explored using Cox regression analysis with hazard ratios and 95% CIs. Adjustments were made for age, sociodemographic variables, and comorbid conditions (with or without cardiovascular disorders).
During a mean of 5.7 years (SD 2.3) of follow-up, totally 1552 patients (19.5%; 803 women and 749 men) had a recorded CHF diagnosis. Thiazides (hazard ratio 0.74, 95% CI 0.65-0.84), vessel-active calcium channel blockers (hazard ratio 0.76, 95% CI 0.67-0.86), and nonselective beta blockers (hazard ratio 0.84, 95% CI 0.72-0.98), with specifically sotalol representing 80% of nonselective beta blockers (hazard ratio 0.81, 95% CI 0.69-0.97), were associated with lower CHF risk in fully adjusted models. Loop diuretics (hazard ratio 1.41, 95% CI 1.25-1.57) were associated with a higher risk. Findings for thiazides and vessel-active channel blockers were consistent in the tested subgroups.
In this clinical setting, we found that thiazides, vessel-active calcium channel blockers, and nonselective beta blockers (specifically sotalol) were associated with a lower risk of incident CHF among patients with atrial fibrillation. The findings of the present study need to be confirmed in other settings.
To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs = 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke.