Abstract
Aims
As large population-based studies of aortic dissection are lacking, the incidence numbers and knowledge about time-trends and sex differences are uncertain. The objective was to ...describe incidence, temporal trends and outcome of aortic dissection with particular emphasis on sex differences.
Methods and results
During the study period 2002–2016, 8057 patients in Sweden were diagnosed with aortic dissection, identified from the National Patient Register and the Cause of Death Register. A total of 5757 (71%) patients were hospitalized, whereas 2300 (29%) patients were deceased without concurrent hospital stay. The annual incidence was 7.2 per 100 000 (9.1 in men and 5.4 in women), decreasing over time in men (P = 0.005). Mean age in the hospitalized patients was 68 years (SD 13), 2080 (36%) were women. Within the first 14 days after onset, 1807 patients (32%) underwent surgical repair. The proportion of surgically treated increased from the 5-year period 2002–2006 to 2012–2016 27% vs. 35%, odds ratio (OR) 1.61, 95% confidence interval (CI) 1.39–1.86; P < 0.001. In hospitalized patients, 30-day mortality decreased between the same periods (26% vs. 21%, OR 0.68, 95% CI 0.59–0.80; P < 0.001). Long-term mortality decreased as well (hazard ratio 0.74, 95% CI 0.67–0.82; P < 0.001). Women had higher 30-day mortality than men after acute repair, a sex difference that remained after age adjustment (17% vs. 12%, OR 1.38, 95% CI 1.04–1.82; P = 0.006).
Conclusion
This population-based study detected a higher incidence of aortic dissection than prior reports, but a decreasing incidence in men. Surgical therapy was increasingly used and with more favourable outcome but was less frequently offered to elderly patients. The sustained sex differences regarding both incidence and outcome require further attention.
Graphical Abstract
Graphical Abstract
Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are ...associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop.
In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular CV mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study.
An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.
The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease ...(CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4232 men and women 60 years of age at the time of recruitment.
Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4 compared with quartile 1 was associated with a hazard ratio of 1.69 (95% confidence interval, 1.30-2.19) after adjustment for sex. Further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes mellitus, smoking, overweight, obesity, physical inactivity, and statin use resulted in a decrease in the hazard ratio to 1.48 (95% confidence interval, 1.12-1.95).
Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation.
BackgroundLow socioeconomic position (SEP) has been demonstrated to negatively influence outcome in several cardiovascular patient groups. The aim of this study was to analyse time trends of ...incidence of intact abdominal aortic aneurysm (iAAA) and ruptured AAA (rAAA), respectively, and to investigate whether SEP had any influence on the probability to present with rupture and, finally, to determine the impact of SEP on outcome.MethodsNationwide population-based study including all individuals with iAAA or rAAA in Sweden during 2001–2015.ResultsThe number of individuals with an AAA was 41 222; the majority were identified as iAAA 33 254 (80.7%) and 7968 (19.3%) as rAAA. Time trends showed decreasing incidence of rAAA but increase in iAAA during the study period. Individuals with low income or low educational level were more likely to present with a rAAA rather than iAAA: OR 2.16 (95 % CI 1.98 to 2.36, p<0.001) and OR 1.33 (95 % CI 1.21 to 1.46, p<0.001), respectively. Low income was also associated with increased 90-day mortality and 1-year mortality after treatment for rAAA, OR 1.42 (95% CI 1.07 to 1.89, p=0.014) and OR 1.39 (95% CI 1.13 to 1.97, p=0.005).ConclusionThis large nationwide study showed a decreasing incidence of rAAA. Individuals with low SEP were found to have an augmented risk of presenting with rAAA rather than iAAA and, in addition, to fare worse after repair. Consequently, SEP should be regarded as a relevant risk factor that should be included in considerations for improved care flow of patients with AAA.
Drug-drug interactions have been shown to affect the risk of fall injuries when opioids are used concomitantly with drugs inhibiting the cytochrome P450 2D6 (CYP2D6) enzyme in a previous ...pharmacoepidemiological study. The aim of this study was to determine whether CYP2D6-inhibiting drugs reinforce the risk of fall injuries when used concomitantly with antidepressants or antipsychotics. We identified all 252,704 adults with a first fall injury leading to hospitalisation from the National Patient Register in Sweden 2006-2013. Data on dispensed drugs was linked from the Swedish Prescribed Drug Register. We applied a case-crossover design to analyse newly dispensed (28 days preceding the fall injury, preceded by a 12-week washout period) antidepressants and antipsychotics, respectively, in relation to risk of a fall injury and according to concomitant use of CYP2D6-inhibiting drugs. Newly dispensed drugs were assessed correspondingly in a control period of equal length, 28 days prior to the 12-week washout period. Overall, the risk of fall injury was increased after newly initiated antidepressant and antipsychotic treatment. For antidepressants, concomitant CYP2D6 inhibitor use further elevated the risk estimates compared to non-use, most pronounced for the groups selective serotonin reuptake inhibitors (sertraline excluded) OR = 1.47 (95% CI 1.19-1.80) vs. OR = 1.19 (95% CI 1.13-1.26), and tricyclic antidepressants OR = 1.71 (95% CI 1.17-2.51) vs. 1.27 (95% CI 1.11-1.47) as well as for sertraline OR = 1.61 (95% CI 1.05-2.38) vs. 1.12 (95% CI 1.00-1.26). For antipsychotics, the risk of fall injury was not altered by concomitant use of CYP2D6-inhibiting drugs. In conclusion, concomitant use of CYP2D6 inhibiting drugs tends to further increase the risk of fall injury in newly initiated antidepressant treatment, but not in antipsychotic treatment.
The use of pesticides has increased during the past decades, also increasing the risk of exposure to toxic pesticides that can cause detrimental health effects in the future. This is of special ...concern among farmers in low-to-middle-income countries that may lack proper training in the safe use of these chemicals. To assess the situation in Bolivia a cross-sectional study in three agricultural communities was performed (n = 297). Handling, use of personal protective equipment (PPE) and pesticide exposure were assessed by a questionnaire and measurements of urinary pesticide metabolites (UPMs). Results showed that methamidophos (65%) and paraquat (52%) were the most commonly used pesticides and that 75% of the farmers combined several pesticides while spraying. Notably, only 17% of the farmers used recommended PPEs while 84% reported to have experienced symptoms of acute pesticide poisoning after spraying. UPM measurements indicated high levels of exposure to chlorpyrifos, pyrethroids and 2,4D and that men generally were more highly exposed compared to women. Our study demonstrates that farmers who are better at following recommendations for pesticide handling and use of PPE had a significantly lower risk of having high UPM levels of most measured pesticides. Our results thus confirm the need of proper training of farmers in low-to-middle-income countries in proper protection and pesticide handling in order to reduce exposure levels and health problems.
Abstract
Malondialdehyde (MDA) is generated in oxidized LDL. It forms covalent protein adducts, and is recognized by antibodies (anti-MDA). We previously studied IgM anti-MDA, and here we focus on ...IgG, IgG1 and IgG2 anti-MDA in predicting cardiovascular disease (CVD). We determined, by ELISA, anti-MDA in a 7-year follow-up of 60-year-old men and women from Stockholm County (2039 men, 2193 women). We identified 210 incident CVD cases (defined as new events of myocardial infarction (MI), and hospitalization for angina pectoris) and ischemic stroke, and 620 age- and sex-matched controls. IgG anti-MDA was not associated with CVD. Median values only differed significantly for IgG1 anti-MDA among men, with lower levels among cases than controls (p = 0.039). High IgG1 anti-MDA (above 75th percentile) was inversely associated with CVD risk after adjustment for smoking, body mass index, type 2 diabetes, hyperlipidemia, and hypertension, (OR and 95% CI: 0.59; 0.40–0.89). After stratification by sex, this association emerged in men (OR and 95% CI: 0.46; 0.27–0.77), but not in women. IgG2 anti-MDA were associated with protection in the whole group and among men though weaker than IgG1 anti-MDA. IgG2 anti-MDA above the 75th percentile was associated with an increased risk of MI/angina in women (OR and 95% CI: 2.57; (1.08–6.16)). IgG1 and less so IgG2 anti-MDA are protection markers for CVD and MI/angina in the whole group and among men. However, IgG2 anti-MDA was a risk marker for MI/angina among women. These findings could have implications for both prediction and therapy.
We aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of ...metabolic syndrome.
We performed our study in a population-based longitudinal cardiovascular study, comprising 1 924 men and 2 097 women, aged 60 years, from Stockholm. Body mass index, waist circumference, sagittal abdominal diameter and components of metabolic syndrome (systolic- and diastolic blood pressure, fasting glucose, triglycerides, high-density lipoprotein-cholesterol) were recorded at baseline. Participants were classified by their body mass index (normal weight, overweight or obese), waist circumference (normal, semi-elevated or elevated), and according to presence of metabolic syndrome. Atrial fibrillation risk was estimated by Cox proportional hazards regression models, adjusted for common atrial fibrillation risk factors, expressed as HR and 95% CI.
During a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: body mass index 1.25 (1.12 - 1.40), waist circumference 1.35 (1.19 - 1.54) and sagittal abdominal diameter 1.28 (1.14 - 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 - 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 - 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 - 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 - 2.87).
Body mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.
Background Studies on intact abdominal aortic aneurysms mainly focus on treated patients, and data on untreated patients are sparse. The objective was to investigate sex differences among untreated ...patients regarding rupture and mortality rates and to determine predictors for these events. Sex-specific causes of death were evaluated. Methods and Results All patients ≥40 years diagnosed from 2001 to 2015 (n=32 393) with intact abdominal aortic aneurysms were identified in national registries; 60% (n=19 569) were untreated. Comorbid loads, crude rupture, and mortality rates were assessed. Predictors of 5-year rupture and mortality were analyzed in Cox models (sex, age, comorbidities, income, and marital status). The proportion of men and women with multiple comorbidities was similar. Within 5 years, 798 ruptures occurred (9.7% women versus 6.9% men,
<0.001). Ruptures were independently predicted by female sex (hazard ratio HR, 1.23; 95% CI, 1.07-1.42;
=0.004), chronic obstructive pulmonary disease (HR, 1.36; 95% CI, 1.15-1.62;
<0.001), age (HR, 11.49; 95% CI, 5.68-23.25 for ≥80 years;
<0.001), and income (HR, 0.63; 95% CI, 0.53-0.75 for highest tertile;
<0.001). After 5 years, 56.5% women and 50.4% men were deceased. Mortality was not independently predicted by female sex. Rupture was the third most common cause of death (11.9% women versus 8.7% men;
<0.001). The median time-to-events was 2.8 years. Conclusions A considerable proportion of patients with intact abdominal aortic aneurysms in surveillance remain untreated. Despite surveillance algorithms, the healthcare system fails to prevent a high number of ruptures, especially among women. The time-to-event data highlight the urgency to develop more individualized surveillance.
Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal ...obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.
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