PURPOSE OF REVIEW:To summarize evidence from recent studies of high lipoprotein(a) as a risk factor for peripheral artery disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Additionally, provide clinicians with 10-year absolute risk charts enabling risk prediction of PAD and AAA by lipoprotein(a) levels and conventional risk factors. RECENT FINDINGS:Numerous studies support high lipoprotein(a) as an independent risk factor for PAD, AAA, and MALE. The strongest evidence is from the Copenhagen General Population Study (CGPS) and the UK Biobank, two large general population-based cohorts. In the CGPS, a 50 mg/dl higher genetically determined lipoprotein(a) associated with hazard ratios of 1.39 (1.24-1.56) for PAD and 1.21 (1.01-1.44) for AAA. Corresponding hazard ratio in the UK Biobank were 1.38 (1.30-1.46) and 1.42 (1.28-1.59). In CGPS participants with levels at least 99th (≥143 mg/dl) vs, less than 50th percentile (≤9 mg/dl), hazard ratios were 2.99 (2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA, with a corresponding incidence rate ratio for MALE of 3.04 (1.55-5.98) in participants with PAD. SUMMARY:Evidence from both observational and genetic studies support high lipoprotein(a) as a causal risk factor for PAD, AAA, and MALE, and highlight the potential of future lipoprotein(a)-lowering therapy to reduce the substantial morbidity and mortality associated with these diseases.

Background: Elevated lipoprotein(a), present in 1 in 5 individuals, is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent studies have reached contrasting conclusions on whether low-grade inflammation measured by elevated C-reactive protein (CRP) modifies the risk of ASCVD from high lipoprotein(a). We tested the hypothesis that high lipoprotein(a) associates with risk of recurrent ASCVD irrespective of elevated or low CRP. Additionally, we performed meta-analyses of previous studies on lipoprotein(a)-associated ASCVD risk stratified by CRP levels and by incident or recurrent events. Methods: We included 3,543 individuals with prevalent ASCVD from the Copenhagen General Population Study (CGPS), a contemporary, prospective Danish cohort study. Hazard ratios (HR) for ASCVD were examined using multivariable adjusted Cox regressions stratified by CRP (<2 mg/L and ≥2 mg/L). Random-effects meta-analyses in primary (incident events) and secondary (recurrent events) prevention were conducted separately, including studies on lipoprotein(a) and risk of ASCVD stratified by CRP. Results: During a median of 7.5 years of follow-up of 3,543 CGPS participants with established ASCVD, 1,425 experienced a recurrent ASCVD event. Multivariable adjusted HRs for ASCVD for high vs. low lipoprotein(a) were 1.41 (95% confidence interval: 1.19-1.67) and 1.31 (1.08-1.59) in individuals with low or elevated CRP with no evidence of effect modification (Figure 1A, p for interaction=0.11). When risk estimates for ASCVD were summarized in separate meta-analyses for primary and secondary prevention settings, a 50 mg/dL higher lipoprotein(a) was robustly associated with increased risk of ASCVD irrespective of CRP levels (Figure 1B). In primary prevention, a 50 mg/dL higher lipoprotein(a) associated with similar summary HRs of 1.18 (1.15-1.20) in low CRP vs. 1.16 (1.14-1.19) in elevated CRP, and likewise in secondary prevention settings, with similar HRs of 1.10 (1.07-1.14) and 1.14 (1.10-1.17), respectively. Conclusion: High lipoprotein(a) was associated with increased risk of ASCVD irrespective of CRP levels both in primary and secondary prevention settings.

PURPOSE OF REVIEW:The aim of this study is to summarize major cardiovascular guideline recommendations on lipoprotein(a) and highlighting recent findings that emphasize how measuring lipoprotein(a) once in all adults is meaningful regardless of age, sex, comorbidities, or ethnicity.RECENT FINDINGS:Many international guidelines now recommend once in a lifetime measurement of lipoprotein(a) in all adult individuals to facilitate accurate risk prediction. Lipoprotein(a)-lowering therapy to reduce cardiovascular disease is on the horizon, with results from the first phase 3 trial expected in 2025.SUMMARY:Elevated lipoprotein(a) is an independent causal risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis and measuring lipoprotein(a) once in all individuals regardless of age, sex, comorbidities, or ethnicity is meaningful to aid in risk stratification.

Aims Recent evidence suggest that the lipoprotein(a)-associated risk of atherosclerotic cardiovascular disease (ASCVD) may be observed only in individuals with low-grade systemic inflammation. It was hypothesized that high lipoprotein(a) is a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis irrespective of C-reactive protein levels. Methods and results A total of 68 090 individuals from the Copenhagen General Population Study, a prospective cohort study, were included. During a median follow-up of 8.1 years, 5104 individuals developed ASCVD, 2432 myocardial infarction, and 1220 aortic valve stenosis. The risk of ASCVD, myocardial infarction, and aortic valve stenosis increased with higher values of both lipoprotein(a) and C-reactive protein. For individuals with lipoprotein(a) in the 91st-100th percentiles (>= 70 mg/dl, >= 147 nmol/l) vs. the 1st-33rd percentiles (<= 6 mg/dl, <= 9 nmol/l), the multivariable-adjusted hazard ratio for ASCVD was 1.61 (95% confidence interval 1.43-1.81) for those with C-reactive protein <2 mg/l and 1.57 (1.36-1.82) for those with C-reactive protein >= 2 mg/l (P for interaction = 0.87). The corresponding values were 2.08 (1.76-2.45) and 1.65 (1.34-2.04) for myocardial infarction, and 2.01 (1.59-2.55) and 1.73 (1.31-2.27) for aortic valve stenosis, respectively (P for interaction = 0.15 and = 0.18). The highest absolute 10-year risks were found in men aged 70-79 years with lipoprotein(a) levels in the 91st-100th percentiles and C-reactive protein >= 2 mg/l, with 34% for ASCVD, 19% for myocardial infarction, and 13% for aortic valve stenosis. The corresponding values in women were 20%, 10%, and 8%, respectively. Conclusion High lipoprotein(a) was a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis independent of C-reactive protein levels.

Introduction: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown. Objective: To investigate associations between a woman’s own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS. Methods: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960–1996, with information on birthweight and measured weight and height at the ages of 7–13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15–50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis. Results: Birthweight was not associated with PCOS. At the age of 7–13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34–3.42) at age 7 years and 2.99 (95% CI 2.38–3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth. Conclusion: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.

Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.Aim: To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC.Subjects and methods: Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.Results: 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively.Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.

Objectives: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that size earlier in life may be important in the aetiology of SLE as well. We investigated whether birthweight, childhood body mass index (BMI; [kg/m(2)]), height and growth are associated with risks of adult SLE. Methods: The study included 346,627 children from the Copenhagen School Health Records Registe (TM), born 1930-1996 with measured weights and heights from 7-13 years. Birthweight information was available from 1936. Linkages were made to the Danish National Patient Register for information on registrations of SLE. During follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazards regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: No differences by sex were detected in any of the associations. Birthweight was not associated with SLE risks. Childhood BMI and height were positively and linearly associated with SLE risks. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. The estimates were similar in magnitude across all childhood ages for BMI and height. There were limited indications that change in BMI or growth in height during childhood influence the risks of SLE in adulthood. Conclusions: Childhood body size is associated with risks of adult SLE, which supports the hypothesis that early life factors are important in SLE aetiology. (C) 2020 Elsevier Inc. All rights reserved.