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2.
Eur J Prev Cardiol ; 31(7): 903-914, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38253342

RESUMO

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease including coronary heart disease, peripheral arterial disease, ischaemic stroke, and calcific aortic valve stenosis. Clinical trials of specific and potent Lp(a)-lowering drugs are currently underway. However, in clinical practice, widespread assessment of Lp(a) is still lacking despite several guideline recommendations to measure Lp(a) at least once in a lifetime in all adults to identify those at high or very high risk due to elevated levels. The present review provides an overview of key findings from observational and genetic Lp(a) studies, highlights the main challenges in observational Lp(a) studies, and proposes a minimum set of requirements to enhance the quality and harmonize the collection of Lp(a)-related data. Adherence to the recommendations set forth in the present manuscript is intended to enhance the quality of future observational Lp(a) studies, to better define thresholds for increased risk, and to better inform clinical trial design. The recommendations can also potentially assist in the interpretation and generalization of clinical trial findings, to improve care of patients with elevated Lp(a) and optimize treatment and prevention of cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Lipoproteína(a) , Humanos , Lipoproteína(a)/sangue , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Biomarcadores/sangue , Medição de Risco , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Pesquisa Biomédica , Medicina Baseada em Evidências
3.
J Am Coll Cardiol ; 82(24): 2265-2276, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38057068

RESUMO

BACKGROUND: Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). OBJECTIVES: The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. METHODS: The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. RESULTS: Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. CONCLUSIONS: High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Doença Arterial Periférica , Feminino , Humanos , Masculino , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/genética , Lipoproteína(a) , Doença Arterial Periférica/epidemiologia , Fatores de Risco
4.
Eur Heart J ; 44(42): 4408-4418, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37632410

RESUMO

BACKGROUND AND AIMS: The aims of this study were to investigate lipid parameters during the first 14-16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14-16 months. METHODS: The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14-16 months (n = 168), was used. RESULTS: Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14-16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14-16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations. CONCLUSIONS: Lipid parameters changed during the first 14-16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14-16 months. These findings increase our knowledge of how lipid traits develop over the first 14-16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.


Assuntos
Apolipoproteínas , Lipídeos , Criança , Recém-Nascido , Humanos , Peso ao Nascer , Triglicerídeos , Colesterol , Apolipoproteínas B , LDL-Colesterol , Lipoproteína(a) , HDL-Colesterol
5.
Eur Heart J ; 44(16): 1449-1460, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-36805188

RESUMO

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.


Assuntos
Estenose da Valva Aórtica , Aterosclerose , Infarto do Miocárdio , Masculino , Humanos , Feminino , Proteína C-Reativa , Lipoproteína(a) , Estudos Prospectivos , Fatores de Risco , Estenose da Valva Aórtica/epidemiologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Aterosclerose/epidemiologia , Valva Aórtica
6.
Ann Neurol ; 93(5): 952-964, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36606557

RESUMO

OBJECTIVE: For decades, it has been suggested that small dense low-density lipoprotein (sdLDL) may be particularly atherogenic. High levels of sdLDL are associated with an increased risk of ischemic heart disease; however, the association of sdLDL with ischemic stroke has not been explored in a large prospective study on the general population. We tested the hypothesis that high sdLDL cholesterol levels are associated with an increased risk of ischemic stroke. METHODS: This prospective study included 38,319 individuals from the Copenhagen General Population Study with fresh sample measurements of sdLDL cholesterol. Median follow-up time was 3.1 years. We observed 302 and 74 ischemic and hemorrhagic strokes from baseline in 2013 to 2017 to the end of follow-up in 2018. For comparison, we included estimates for large buoyant LDL cholesterol and total LDL cholesterol. RESULTS: Higher levels of sdLDL cholesterol were log-linearly associated with increased risk of ischemic stroke. Compared with individuals with sdLDL cholesterol in the lowest tertile (≤0.60 mmol/l; ≤23 mg/dl) the multivariable adjusted hazard ratio for ischemic stroke was 1.79 (95% confidence interval = 1.31-2.43) for the highest tertile (≥0.86 mmol/l; ≥33 mg/dl). Multivariable adjusted hazard ratios for ischemic stroke per 1 mmol/l (38.7 mg/dl) higher levels were 1.69 (1.28-2.22) for sdLDL cholesterol, 0.95 (0.78-1.16) for large buoyant LDL cholesterol, and 1.08 (0.93-1.25) for total LDL cholesterol. Hazard ratios were similar when further adjusting for body mass index (BMI) and diabetes mellitus in the biological pathway in combination with related lipids and lipoproteins. INTERPRETATION: Higher sdLDL cholesterol levels were robustly associated with increased risk of ischemic stroke. ANN NEUROL 2023;93:952-964.


Assuntos
Aterosclerose , AVC Isquêmico , Humanos , LDL-Colesterol , Estudos Prospectivos , Aterosclerose/epidemiologia , Lipoproteínas , Fatores de Risco
8.
J Am Coll Cardiol ; 81(2): 136-152, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36631208

RESUMO

BACKGROUND: It is unclear whether elevated low-density lipoprotein (LDL) triglycerides are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). OBJECTIVES: This study tested the hypothesis that elevated LDL triglycerides are associated with an increased risk of ASCVD and of each ASCVD component individually. METHODS: The study investigators used the Copenhagen General Population Study, which measured LDL triglycerides in 38,081 individuals with a direct automated assay (direct LDL triglycerides) and in another 30,208 individuals with nuclear magnetic resonance (NMR) spectroscopy (NMR LDL triglycerides). Meta-analyses aggregated the present findings with previously reported results. RESULTS: During a median follow-up of 3.0 and 9.2 years, respectively, 872 and 5,766 individuals in the 2 cohorts received a diagnosis of ASCVD. Per 0.1 mmol/L (9 mg/dL) higher direct LDL triglycerides, HRs were 1.26 (95% CI: 1.17-1.35) for ASCVD, 1.27 (95% CI: 1.16-1.39) for ischemic heart disease, 1.28 (95% CI: 1.11-1.48) for myocardial infarction, 1.22 (95% CI: 1.08-1.38) for ischemic stroke, and 1.38 (95% CI: 1.21-1.58) for peripheral artery disease. Corresponding HRs for NMR LDL triglycerides were 1.26 (95% CI: 1.20-1.33), 1.33 (95% CI: 1.25-1.41), 1.41 (95% CI: 1.31-1.52), 1.13 (95% CI: 1.05-1.23), and 1.26 (95% CI: 1.10-1.43), respectively. The foregoing results were not entirely statistically explained by apolipoprotein B levels. In meta-analyses for the highest quartile vs the lowest quartile of LDL triglycerides, random-effects risk ratios were 1.50 (95% CI: 1.35-1.66) for ASCVD (4 studies; 71,526 individuals; 8,576 events), 1.62 (95% CI: 1.37-1.93) for ischemic heart disease (6 studies; 107,538 individuals; 9,734 events), 1.30 (95% CI: 1.13-1.49) for ischemic stroke (4 studies; 78,026 individuals; 4,273 events), and 1.53 (95% CI: 1.29-1.81) for peripheral artery disease (4 studies; 107,511 individuals; 1,848 events). CONCLUSIONS: Elevated LDL triglycerides were robustly associated with an increased risk of ASCVD and of each ASCVD component individually in 2 prospective cohort studies and in meta-analyses of previous and present studies combined.


Assuntos
Aterosclerose , Hipertrigliceridemia , AVC Isquêmico , Lipoproteínas LDL , Triglicerídeos , Humanos , Aterosclerose/complicações , Aterosclerose/diagnóstico , LDL-Colesterol , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Isquemia Miocárdica/diagnóstico , Doença Arterial Periférica/diagnóstico , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Triglicerídeos/química , Lipoproteínas LDL/sangue , Lipoproteínas LDL/química
9.
Clin Chem Lab Med ; 61(2): 275-284, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36377310

RESUMO

OBJECTIVES: Red blood cell parameters are frequently used biomarkers when assessing clinical status in newborns and in early childhood. Cell counts, amounts, and concentrations of these parameters change through gestation and after birth. Robust age-specific reference intervals are needed to optimize clinical decision making. METHODS: The Copenhagen Baby Heart Study (CBHS) and the COMPARE study are prospective cohort studies including red blood cell parameters from 7,938 umbilical cord blood samples and 295 parallel venous blood samples from newborns with follow-up at two and at 14-16 months after birth. RESULTS: For venous blood at birth, reference intervals for hemoglobin, erythrocytes, and hematocrit were 145-224 g/L, 4.1-6.4 × 1012/L, and 0.44-0.64, respectively. Hemoglobin, erythrocytes, and hematocrit were lower at birth in children delivered by prelabor cesarean section compared to vaginal delivery. Conversion algorithms based on term newborns were: venous hemoglobin=(umbilical cord hemoglobin-86.4)/0.39; venous erythrocytes=(umbilical cord erythrocytes-2.20)/0.44; and venous hematocrit=(umbilical cord hematocrit-0.24)/0.45. CONCLUSIONS: This study presents new reference intervals for red blood cell parameters in early childhood, describes the impact of delivery mode, and provide exact functions for converting umbilical cord to venous blood measurements for term newborns. These findings may improve clinical decision making within neonatology and infancy and enhance our clinical understanding of red blood cell parameters for health and diseases in early life.


Assuntos
Cesárea , Sangue Fetal , Feminino , Humanos , Recém-Nascido , Gravidez , Eritrócitos , Hemoglobinas , Estudos Prospectivos , Lactente
10.
JAMA Netw Open ; 5(11): e2243146, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409493

RESUMO

Importance: Kidney functional capacity is low at birth but doubles during the first 2 weeks of life and reaches near-adult levels at age 1 to 2 years. Existing reference intervals for markers of kidney function in newborns are mostly based on preterm newborns, newborns with illness, or small cohorts of term newborns, and the consequences of maternal comorbidities for newborn kidney function are sparsely described. Objective: To establish robust reference intervals for creatinine and urea in healthy children in early childhood and to assess whether maternal comorbidity is associated with newborn creatinine and urea concentrations. Design, Setting, and Participants: This multicenter, prospective, population-based cohort study assessed data and umbilical cord blood samples from participants in the Copenhagen Baby Heart Study (CBHS) who were born between April 1, 2016, and October 31, 2018, and venous blood samples from a subsample of CBHS participants who were enrolled in the COMPARE study between May 3, 2017, and November 4, 2018. Cord blood samples of 13 354 newborns from the CBHS and corresponding venous blood samples of 444 of those newborns from the COMPARE study were included. Blood samples were collected at birth, age 2 months, and age 14 to 16 months, with follow-up completed on February 12, 2020. Healthy nonadmitted term newborns from maternity wards at 3 hospitals in the Capital Region of Denmark were included. Exposures: Maternal comorbidity. Main Outcomes and Measures: Creatinine and urea concentrations. Results: Among 13 354 newborns in the CBHS cohort, characteristics of 12 938 children were stratified by sex and gestational age (GA). Of those, 6567 children (50.8%) were male; 5259 children (40.6%) were born at 37 to 39 weeks' GA, and 7679 children (59.4%) were born at 40 to 42 weeks' GA. Compared with children born at 40 to 42 weeks' GA, those born at 37 to 39 weeks' GA had lower birth weight, Apgar scores at 5 minutes, placental weight, and placental-fetal weight ratio. Children born at 37 to 39 weeks' GA vs those born at 40 to 42 weeks' GA were more frequently small for GA at birth and more likely to have placental insufficiency and exposure to maternal preeclampsia, maternal diabetes, maternal kidney disease, and maternal hypertension. Among children born at 37 to 39 weeks' GA, reference intervals were 0.54 to 1.08 mg/dL for creatinine and 5.32 to 14.67 mg/dL for urea; among children born at 40 to 42 weeks' GA, reference intervals were 0.57 to 1.19 mg/dL for creatinine and 5.60 to 14.85 mg/dL for urea. At birth, multifactorially adjusted odds ratios among children exposed to preeclampsia were 9.40 (95% CI, 1.68-52.54) for a venous creatinine concentration higher than the upper reference limit, 4.29 (95% CI, 1.32-13.93) for a venous creatinine concentration higher than the 90th percentile, and 3.10 (95% CI, 1.14-8.46) for a venous creatinine concentration higher than the 80th percentile. Conclusions and Relevance: In this study, improved reference intervals for creatinine and urea concentrations were generated. Preeclampsia was associated with an increased risk of high newborn creatinine concentrations, suggesting that newborns of mothers with preeclampsia need closer observation of their kidney function.


Assuntos
Pré-Eclâmpsia , Lactente , Adulto , Criança , Recém-Nascido , Humanos , Pré-Escolar , Masculino , Feminino , Gravidez , Estudos de Coortes , Estudos Prospectivos , Creatinina , Placenta , Comorbidade , Ureia , Rim
11.
Atherosclerosis ; 349: 7-16, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35606078

RESUMO

Rates of atherosclerotic cardiovascular diseases (CVD) in the Western world have spectacularly decreased over the past 50 years. However, a substantial proportion of high-risk patients still develop heart attacks, strokes and valvular heart diseases despite benefiting from state-of-the-art treatments including lipid-lowering therapies. Over the past 10-15 years, it has become increasingly clear that Lipoprotein(a) (Lp[a]) is a critical component of this so-called residual risk. Genetic association studies revealed that Lp(a) is robustly, independently and causally associated with a broad range of cardiovascular and valvular heart diseases. Up to 1 billion people around the globe may have an Lp(a) level that places them in a high-risk category. Lp(a) is strongly associated with calcific aortic valve stenosis (CAVS), coronary artery disease (CAD), peripheral arterial disease (PAD) and to a lesser extent with ischemic stroke (IS) and heart failure (HF). Because of this strong association with cardiovascular and valvular heart diseases, Lp(a) even emerged as one of the most important genetic determinants of human lifespan and healthspan. Here, we review the evidence from the largest and most informative genetic association studies and prospective studies that have investigated the association between Lp(a) and human lifespan, healthspan, CVD, CAVS and non-cardiovascular diseases. We present Lp(a) threshold values that may be clinically relevant and identify other cardiovascular risk factors that may modulate the absolute risk of CVD in individuals with high Lp(a) levels. Finally, we identify key clinical and research questions that require further investigation to eventually and optimally reduce CVD risk in patients with high Lp(a) levels.


Assuntos
Estenose da Valva Aórtica , Calcinose , Doenças Cardiovasculares , Valva Aórtica/patologia , Estenose da Valva Aórtica/tratamento farmacológico , Biomarcadores , Calcinose/tratamento farmacológico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Humanos , Lipoproteína(a)/genética , Estudos Prospectivos , Fatores de Risco
12.
J Am Coll Cardiol ; 79(6): 545-558, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35144746

RESUMO

BACKGROUND: High plasma lipoprotein(a) and high body mass index are both causal risk factors for calcific aortic valve disease. OBJECTIVES: This study sought to test the hypothesis that risk of calcific aortic valve disease is the highest when both plasma lipoprotein(a) and body mass index are extremely high. METHODS: From the Copenhagen General Population Study, we used information on 69,988 randomly selected individuals recruited from 2003 to 2015 (median follow-up 7.4 years) to evaluate the association between high lipoprotein(a) and high body mass index with risk of calcific aortic valve disease. RESULTS: Compared with individuals in the 1st to 49th percentiles for both lipoprotein(a) and body mass index, the multivariable adjusted HRs for calcific aortic valve disease were 1.6 (95% CI: 1.3-1.9) for the 50th to 89th percentiles of both (16% of all individuals) and 3.5 (95% CI: 2.5-5.1) for the 90th to 100th percentiles of both (1.1%) (P for interaction = 0.92). The 10-year absolute risk of calcific aortic valve disease increased with higher lipoprotein(a), body mass index, and age, and was higher in men than in women. For women and men 70-79 years of age with body mass index ≥30.0 kg/m2, 10-year absolute risks were 5% and 8% for lipoprotein(a) ≤42 mg/dL (88 nmol/L), 7% and 11% for 42-79 mg/dL (89-169 nmol/L), and 9% and 14% for lipoprotein(a) ≥80 mg/dL (170 nmol/L), respectively. CONCLUSIONS: Extremely high lipoprotein(a) levels and extremely high body mass index together conferred a 3.5-fold risk of calcific aortic valve disease. Ten-year absolute risk of calcific aortic valve disease by categories of lipoprotein(a) levels, body mass index, age, and sex ranged from 0.4% to 14%.


Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Índice de Massa Corporal , Calcinose/sangue , Previsões , Lipoproteína(a)/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Biomarcadores/sangue , Calcinose/diagnóstico , Calcinose/epidemiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Clin Chem Lab Med ; 60(2): 261-270, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34752018

RESUMO

OBJECTIVES: The coagulation system is not fully developed at birth and matures during the first months of infancy, complicating clinical decision making within hemostasis. This study evaluates coagulation parameters at birth and two months after birth, and tests whether cord blood can be used as a proxy for neonatal venous blood measurements. METHODS: The Copenhagen Baby Heart Study (CBHS) and the COMPARE study comprise 13,237 cord blood samples and 444 parallel neonatal venous blood samples, with a two month follow-up in 362 children. RESULTS: Because coagulation parameters differed according to gestational age (GA), all analyses were stratified by GA. For neonatal venous blood, reference intervals for activated partial thromboplastin time (APTT) and prothrombin time (PT) were 28-43 s and 33-61% for GA 37-39 and 24-38 s and 30-65% for GA 40-42. Reference intervals for international normalized ratio (INR) and thrombocyte count were 1.1-1.7 and 194-409 × 109/L for GA 37-39 and 1.2-1.8 and 188-433 × 109/L for GA 40-42. Correlation coefficients between umbilical cord and neonatal venous blood for APTT, PT, INR, and thrombocyte count were 0.68, 0.72, 0.69, and 0.77 respectively, and the distributions of the parameters did not differ between the two types of blood (all p-values>0.05). CONCLUSIONS: This study describes new GA dependent reference intervals for common coagulation parameters in newborns and suggests that cord blood may serve as a proxy for neonatal venous blood for these traits. Such data will likely improve clinical decision making within hemostasis among newborn and infant children.


Assuntos
Coagulação Sanguínea , Hemostasia , Testes de Coagulação Sanguínea , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Tromboplastina Parcial , Tempo de Protrombina
14.
J Clin Endocrinol Metab ; 107(2): 324-335, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34618900

RESUMO

BACKGROUND AND OBJECTIVE: High lipoprotein(a) is a genetically determined causal risk factor for cardiovascular disease, and 20% of the adult population has high levels (ie, >42 mg/dL, >88 nmol/L). We investigated whether early life lipoprotein(a) levels measured in cord blood may serve as a proxy for neonatal venous blood levels, whether lipoprotein(a) birth levels (ie, cord or venous) predict levels later in life, and whether early life and parental levels correlate. METHODS: The Compare study is a prospective cohort study of newborns (N = 450) from Copenhagen, Denmark, including blood sampling of parents. Plasma lipoprotein(a) was measured in cord blood (N = 402), neonatal venous blood (N = 356), and at 2 (N = 320) and 15 months follow-up (N = 148) of infants, and in parents (N = 705). RESULTS: Mean lipoprotein(a) levels were 2.2 (95% CI, 1.9-2.5), 2.4 (2.0-2.7), 4.1 (3.4-4.9), and 14.6 (11.4-17.9) mg/dL in cord, neonatal venous, and 2- and 15-month venous samples, respectively. Lipoprotein(a) levels in cord blood correlated strongly with neonatal venous blood levels (R2 = 0.95, P < 0.001) and neonatal levels correlated moderately with 2- and 15-month levels (R2 = 0.68 and 0.67, both P < 0.001). Birth levels ≥ 90th percentile predicted lipoprotein(a) > 42 mg/dL at 15 months with positive predictive values of 89% and 85% for neonatal venous and cord blood. Neonatal and infant levels correlated weakly with parental levels, most pronounced at 15 months (R2 = 0.22, P < 0.001). CONCLUSIONS: Lipoprotein(a) levels are low in early life, cord blood may serve as a proxy for neonatal venous blood, and birth levels ≥ 90th percentile can identify newborns at risk of developing high levels.


Assuntos
Doenças Cardiovasculares/epidemiologia , Sangue Fetal/química , Lipoproteína(a)/sangue , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Dinamarca , Feminino , Seguimentos , Fatores de Risco de Doenças Cardíacas , Humanos , Lactente , Recém-Nascido , Lipoproteína(a)/metabolismo , Masculino , Idade Materna , Pais , Estudos Prospectivos
15.
Arterioscler Thromb Vasc Biol ; 42(1): e48-e60, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34647487

RESUMO

High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.


Assuntos
Aterosclerose/genética , Lipoproteína(a)/genética , American Heart Association , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Consenso , Medicina Baseada em Evidências , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Humanos , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Prevalência , Prognóstico , Medição de Risco , Estados Unidos
16.
Atherosclerosis ; 349: 166-174, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34903381

RESUMO

BACKGROUND AND AIMS: We tested the hypotheses (i) that elevated lipoprotein(a) is causally associated with both mitral and aortic valve calcification and disease, and (ii) that aortic valve calcification mediates the effect of elevated lipoprotein(a) on aortic valve stenosis. METHODS: From the Copenhagen General Population study, we included 12,006 individuals who underwent cardiac computed tomography to measure mitral and aortic valve calcification and 85,884 to examine risk of heart valve disease. Participants had information on plasma lipoprotein(a) and genetic instruments associated with plasma lipoprotein(a) to investigate potential causality. RESULTS: At age 70-79 years, 29% and 54% had mitral and aortic valve calcification, respectively. For 10-fold higher lipoprotein(a) levels, multifactorially adjusted odds ratios for mitral and aortic valve calcification were 1.26 (95% confidence interval: 1.13-1.41) and 1.62 (1.48-1.77). For mitral and aortic valve stenosis, corresponding hazard ratios were 0.93 (95%CI:0.40-2.15, 19 events) and 1.54 (1.38-1.71, 1158 events), respectively. For ≤23 versus ≥36 kringle IV type 2 number of repeats, the age and sex adjusted odds ratios for mitral and aortic valve calcification were 1.53 (1.18-1.99) and 2.23 (1.81-2.76). For carriers versus non-carriers of LPA rs10455872, odds ratios for mitral and aortic valve calcification were 1.33 (1.13-1.57) and 1.86 (1.64-2.13). For aortic valve stenosis, 31% (95%CI:16%-76%) of the effect of lipoprotein(a) was mediated through calcification. CONCLUSIONS: Elevated lipoprotein(a) was genetically and observationally associated with mitral and aortic valve calcification and aortic valve stenosis. Aortic valve calcification mediated 31% of the effect of elevated lipoprotein(a) on aortic valve stenosis.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/genética , Calcinose , Humanos , Lipoproteína(a) , Fatores de Risco
17.
Eur Heart J ; 42(12): 1147-1156, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33724357

RESUMO

AIMS: With the current focus on lipoprotein(a) as a likely causal risk factor for cardiovascular disease and new drugs potentially on the market to lower lipoprotein(a) levels, the safety of lowering lipoprotein(a) to low levels becomes increasingly important. We tested whether low levels of lipoprotein(a) and corresponding LPA genotypes associate with major disease groups including cancers and infectious disease. METHODS AND RESULTS: We included 109 440 individuals from the Copenhagen General Population Study. For main World Health Organization International Classification of Diseases 10th edition chapter diseases, the only concordant association of low levels of lipoprotein(a) plasma levels and corresponding LPA genotypes with risk of disease was with low risk of diseases of the circulatory system. Furthermore, no concordant association of low levels of lipoprotein(a) plasma levels and corresponding LPA genotypes with the risk of any cancer (i.e. cancer subtypes combined) or infectious disease was seen. The hazard ratio for the risk of any cancer was 1.06 [95% confidence interval (CI): 0.97-1.15] for the first vs. the fourth quartile of lipoprotein(a), 1.02 (0.97-1.07) for the fourth vs. the first quartile of KIV-2 number of repeats, and 1.01 (0.96-1.07) for rs10455872 non-carriers vs. carriers. The corresponding hazard ratios for the risk of hospitalization for infection were 1.05 (95% CI: 0.99-1.10), 1.02 (0.98-1.07), and 0.97 (0.93-1.03), respectively. CONCLUSION: In a large, contemporary, general population cohort, apart from the well-established association with cardiovascular disease, low levels of lipoprotein(a) and corresponding LPA genotypes did not concordantly associate with any major disease groups including cancers and infections. There is no safety signal from our results to indicate that low levels of lipoprotein(a) are harmful.


Assuntos
Doenças Cardiovasculares , Lipoproteína(a) , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Genótipo , Humanos , Lipoproteína(a)/genética , Fatores de Risco
18.
J Clin Microbiol ; 59(5)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33574119

RESUMO

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Imunoensaio , Infecções por Citomegalovirus , Ensaio de Imunoadsorção Enzimática , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Imunoglobulina G/isolamento & purificação , Imunoglobulina M/isolamento & purificação , Laboratórios , SARS-CoV-2 , Sensibilidade e Especificidade
19.
Clin Chem ; 67(1): 154-166, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33236085

RESUMO

BACKGROUND: High lipoprotein(a) concentrations present in 10%-20% of the population have long been linked to increased risk of ischemic cardiovascular disease. It is unclear whether high concentrations represent an unmet medical need. Lipoprotein(a) is currently not a target for treatment to prevent cardiovascular disease. CONTENT: The present review summarizes evidence of causality for high lipoprotein(a) concentrations gained from large genetic epidemiologic studies and discusses measurements of lipoprotein(a) and future treatment options for high values found in an estimated >1 billion individuals worldwide. SUMMARY: Evidence from mechanistic, observational, and genetic studies support a causal role of lipoprotein(a) in the development of cardiovascular disease, including coronary heart disease and peripheral arterial disease, as well as aortic valve stenosis, and likely also ischemic stroke. Effect sizes are most pronounced for myocardial infarction, peripheral arterial disease, and aortic valve stenosis where high lipoprotein(a) concentrations predict 2- to 3-fold increases in risk. Lipoprotein(a) measurements should be performed using well-validated assays with traceability to a recognized calibrator to ensure common cut-offs for high concentrations and risk assessment. Randomized cardiovascular outcome trials are needed to provide final evidence of causality and to assess the potential clinical benefit of novel, potent lipoprotein(a) lowering therapies.


Assuntos
Doenças Cardiovasculares/etiologia , Lipoproteína(a)/metabolismo , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Humanos , Lipoproteína(a)/análise , Lipoproteína(a)/genética , Análise da Randomização Mendeliana
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