Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank.

BACKGROUND AND AIMS: Elevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights into the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort. METHODS: This was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a). RESULTS: The study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period. CONCLUSIONS: The association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.

Burden of elevated lipoprotein(a) among patients with atherosclerotic cardiovascular disease: Evidence from a systematic literature review and feasibility assessment of meta-analysis.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We aimed to report the burden of clinically relevant elevated Lp(a) in secondary prevention ASCVD population as the evaluation of such evidence is lacking. METHODS: A systematic literature review (SLR) was conducted using Embase®, MEDLINE®, and MEDLINE® In-Process databases to identify studies reporting burden of elevated Lp(a) levels from January 1, 2010, to March 28, 2022. Full-text, English-language studies including ≥500 participants with ≥1 Lp(a) assessment were included. RESULTS: Sixty-one studies reported clinical burden of elevated Lp(a). Of these, 25 observational studies and one clinical trial reported clinical burden of clinically relevant elevated Lp(a) levels. Major clinical outcomes included major adverse cardiovascular event (MACE; n = 20), myocardial infarction (MI; n = 11), revascularization (n = 10), stroke (n = 10), cardiovascular (CV) mortality (n = 9), and all-cause mortality (n = 10). Elevated Lp(a) levels significantly increased the risk of MACE (n = 15) and revascularization (n = 8), while they demonstrated a trend for positive association with remaining CV outcomes. Meta-analysis was not feasible for included studies due to heterogeneity in Lp(a) thresholds, outcome definitions, and patient characteristics. Three studies reported humanistic burden. Patients with elevated Lp(a) levels had higher odds of manifesting cognitive impairment (odds ratio [OR] [95% confidence interval; CI]: 1.62 [1.11-2.37]) and disability related to stroke (OR [95% CI]:1.46 [1.23-1.72)]) (n = 2). Elevated Lp(a) levels negatively correlated with health-related quality of life (R = -0.166, p = 0.014) (n = 1). A single study reported no association between elevated Lp(a) levels and economic burden. CONCLUSIONS: This SLR demonstrated a significant association of elevated Lp(a) levels with major CV outcomes and increased humanistic burden in secondary prevention ASCVD population. These results reinforce the need to quantify and manage Lp(a) for CV risk reduction and to perform further studies to characterize the economic burden.

Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden.

OBJECTIVES: To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. DESIGN: Retrospective, non-interventional cohort study. SETTING: Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Västerbotten). PARTICIPANTS: Patients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. OUTCOME MEASURES: HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. RESULTS: Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs. CONCLUSIONS: HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

Burden and Quality of Life Among Female and Male Patients with Heart Failure in Europe: A Real-World Cross-Sectional Study.

PURPOSE: To characterize symptoms, clinical burden, and health-related quality of life (HRQoL) among women and men with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≤60% in Europe. PATIENTS AND METHODS: A real-world cross-sectional study was conducted in France, Germany, Italy, Spain, and United Kingdom from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive patients with HF. The same patients were invited to complete a questionnaire comprising patient-reported outcomes: the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-level five-dimension EuroQol questionnaire (EQ-5D-5L), Visual Analogue Scale (VAS), and Work Productivity and Activity Impairment questionnaire. RESULTS: The mean age of 804 patients (men, n=517; women, n=287) was 68.6 years (men, 67.8 years; women, 70.2 years; p=0.0022). The mean LVEF was 44.7% (men, 43.6%; women, 46.8%; p<0.0001). Patients reported dyspnoea when active (overall, 55.7%; men, 56.0%; women, 55.3%), fatigue/weakness/faintness (34.5%; men, 32.9%; women, 37.2%), and oedema (20.3%; men, 18.7%; women, 23.1%) as the most troublesome HF symptoms. Overall, 54.1% of patients reported low mood/depression (men, 50.8%; women, 60.1%). The overall MLHFQ mean score was higher (ie, poorer HRQoL) among women vs men (37.9 vs 34.6; p=0.0481). MLHFQ was consistently higher (ie, poorer HRQoL) for women vs men across the physical (18.6 vs 16.6; p=0.0041) and emotional (9.4 vs 7.9; p=0.0021) scoring domains. Mean EQ-5D utility (0.69 vs 0.75; p=0.0046) and VAS scores (55.4 vs 61.3; p<0.0001) were lower among women compared with men. Overall, 23.4% of patients were hospitalized owing to HF in the previous year (men, 22.7%; women, 24.6%). Patients reported 43.2% activity impairment due to HF (men, 41.6%; women, 46.4%; p=0.01). CONCLUSION: HF causes a substantial burden on patients, with a greater burden among women vs men. This gender-related difference is consistent with other HF studies, warranting further research to understand the underlying reasons.

Caregivers of Patients with Heart Failure: Burden and the Determinants of Health-Related Quality of Life.

PURPOSE: To assess the burden among caregivers of patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤60%. The burden by New York Heart Association (NYHA) functional class was also characterized. PATIENTS AND METHODS: A cross-sectional study was conducted in France, Germany, Italy, Spain, and UK from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive HF patients. Caregivers who accompanied the patient to their consultation completed a caregiver self-completion survey voluntarily, which included the Family Caregiver Quality of Life Questionnaire (FAMQOL) and 5-level 5-dimension EuroQol questionnaire (EQ-5D-5L). RESULTS: We analyzed 361 caregivers of patients with HF (NYHA class I, n=41; II, n=212; III IV, n=108). Mean age of caregivers was 58.8 years (NYHA I/II/III-IV: 59.1/60.8/54.6 years; p=0.0029), with majority being females (73.1%). Caregivers spent on average 19.8 hours/week caring for a HF patient, which increased with increase in NYHA class (I/II/III-IV: 11.8/18.1/25.9 hours/week; p=0.0094). Caregivers (24.1%) reported providing emotional support/encouragement to patients as the most troublesome/inconvenient caregiving activity (no significant difference across NYHA class). Nearly one-third of caregivers experienced stress (NYHA I/II/III-IV: 17.1%/28.8%/40.7%; p=0.0111) and anxiety (26.8%/24.1%/39.8%; p=0.0127) due to caregiving burden. The overall FAMQOL mean score decreased significantly (poorer QoL) with increase in NYHA class (I/II/III-IV: 58.1/56.3/52.2; p=0.0069). A trend of decreasing scores with increasing NYHA class was observed across physical, emotional, and social domains (each p≤0.012). CONCLUSION: Caregivers of HF patients with LVEF ≤60% experienced a significant burden, which was higher among caregivers of patients with more severe and symptomatic disease.

Recurrent heart failure hospitalizations increase the risk of cardiovascular and all-cause mortality in patients with heart failure in Sweden: a real-world study.

AIMS: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. METHODS AND RESULTS: Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all-cause mortality were evaluated. A time-dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction-based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all-cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all-cause mortality increased approximately six-fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24-7.48] and 5.59 [4.70-6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. CONCLUSIONS: There is a strong association between recurrent HFHs and CV and all-cause mortality, with the risk increasing progressively with each recurrent HFH.

Heart failure signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan in primary care and cardiologist settings in Germany.

AIMS: The aim of this paper was to analyse heart failure (HF) signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan (sac/val) in primary care and cardiology settings in Germany. METHODS AND RESULTS: A retrospective cohort study of electronic medical records identified 1263 adults (aged ≥18 years) in the German IMS® Disease Analyzer database who were prescribed sac/val during 2016 and had at least 6 months of data following sac/val initiation. Clinical characteristics were collected during the 12 months before the first recorded sac/val prescription (index date) and 6 months post-index. Details of sac/val dose and prescription patterns were also recorded in the 6 months post-index. HF signs, symptoms, and all-cause hospital referrals were evaluated for 90 days pre-index and 30-120 days post-index. Most patients (62%) were prescribed the lowest sac/val dose of 24/26 mg twice daily (b.i.d.) at index; only 14% of patients initiated on 24/26 mg or 49/51 mg b.i.d. were up-titrated to the 97/103 mg b.i.d. target dose during the 6 months post-index, while 6% of patients initiated on either 49/51 mg or 97/103 mg b.i.d. were stably down-titrated. Evaluation of prescription patterns in relation to clinical characteristics did not clearly explain the reluctance to up-titrate in the majority of patients. More patients experienced HF signs or symptoms or all-cause referrals to hospital during the 90 days pre-index than during the 30-120 days post-index. CONCLUSIONS: The majority of patients receiving sac/val are not up-titrated, contrary to recommendations of the EU summary of product characteristics; this is not fully explained by patients' clinical characteristics. Further research is required to understand the reasons for clinician inertia.