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Objective Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF).Methods This retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients.Results Overall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (p

Objectives: Peripartum cardiomyopathy (PPCM) is a rare disease carrying a risk of death and chronic heart failure.It is unknown if women with PPCM have a family history of heart failure. We investigated the prevalence of heart failure and hypertension in first-degree relatives to women with PPCM.Methods: A cohort of 61 women with PPCM was identified through the nationwide Danish registers from 2005 to 2014, and each individual diagnosis of PPCM was validated through review of patient records. We excluded 13 women due to lack of data on relatives. In a case-control design, the 48 remaining women were matched (on age, year of childbirth, parity and number of siblings) to 477 birth-giving Danish women without heart failure. We obtained information on first-degree relatives (parents and siblings) through the National Danish Registers.Results: The cohort of 48 women with PPCM had a mean age of 31 years (SD 6). The prevalence of heart failure in any first-degree relative was higher in women with PPCM, compared with controls (23% vs 10%, p=0.011). A first-degree relative with any cardiovascular diagnosis was not more frequent in women with PPCM versus controls (77% vs 70%, p=0.280), but for siblings only, any cardiovascular diagnosis was more frequent in siblings to women with PPCM (29% vs 16%, p=0.026).Conclusion: Having a first-degree relative with heart failure was significantly more frequent in a cohort of validated PPCM cases than in controls, supporting the notion of shared aetiology between PPCM and other forms of heart failure. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans.Methods and Results: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the PLA2G7 locus associated with either Lp-PLA2 mass or activity (rs7756935, rs1421368, rs1805017 and rs4498351). Genetic association studies were performed in eight cohorts: Quebec-CAVS (1009 cases/1017 controls), UK Biobank (1350 cases/349 043 controls), European Prospective Investigation into Cancer and Nutrition-Norfolk (504 cases/20 307 controls), Genetic Epidemiology Research on Aging (3469 cases/51 723 controls), Malmö Diet and Cancer Study (682 cases/5963 controls) and three French cohorts (3123 cases/6532 controls), totalling 10 137 CAVS cases and 434 585 controls. A fixed-effect meta-analysis using the inverse-variance weighted method revealed that none of the four SNPs was associated with CAVS (OR=0.99 (95% CI 0.96 to 1.02, p=0.55) for rs7756935, 0.97 (95% CI 0.93 to 1.01, p=0.11) for rs1421368, 1.00 (95% CI 1.00 to 1.01, p=0.29) for rs1805017, and 1.00 (95% CI 0.97 to 1.04, p=0.87) for rs4498351).Conclusions: Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS. [ABSTRACT FROM AUTHOR]

Objective: Vascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke.Methods: VEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46-68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels.Results: During a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF.Conclusions: Increased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF. [ABSTRACT FROM AUTHOR]

Aims: High red cell distribution width (RDW) is a strong prognostic factor in patients with cardiovascular disease. We investigated the association between RDW and incidence of acute coronary events (CEs) and fatal outcome in subjects who subsequently experienced a first CE. Methods: and results RDW was measured in 26 820 subjects (aged 45-73 years, 61.6% women), without history of myocardial infarction or stroke, who participated in the Malmö Diet and Cancer study during 1991-1996. Cox proportional hazards model was used to analyse the association between RDW and CE. During a mean follow-up of 14 years, 1995 subjects had a first CE, of which 415 subjects died on the same day as the CE (fatal on day 1), another 86 died within 28 days (fatal in 28 days) and 1494 were non-fatal (survived >28 days). After adjustment for risk factors, baseline RDW was significantly associated with incidence of fatal CE (HR 1.82, CI 1.35 to 2.44) but not with non-fatal CE (HR 0.96, CI 0.82 to 1.12). Among all subjects with a CE during follow-up, the proportion who died on day 1 was 13.7%, 18.2%, 22.5% and 26.7%, respectively, for first, second, third and fourth quartiles of RDW. Conclusions: In this population-based study of subjects without history of CE or stroke, high RDW was associated with increased incidence of fatal CE. No relationship was observed for incidence of non-fatal CE. [ABSTRACT FROM AUTHOR]