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Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

Context: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. Objective: This study aimed to study cardiovascular and metabolic morbidity in CAH. Design,... Full description

Journal Title: Journal of Clinical Endocrinology and Metabolism 2015-09, Vol.100 (9), p.3520-3528
Main Author: Falhammar, Henrik
Other Authors: Frisén, Louise , Hirschberg, Angelica Linden , Norrby, Christina , Almqvist, Catarina , Nordenskjöld, Agneta , Nordenström, Anna
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Endocrine Society
ID: ISSN: 0021-972X
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title: Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study
format: Article
creator:
  • Falhammar, Henrik
  • Frisén, Louise
  • Hirschberg, Angelica Linden
  • Norrby, Christina
  • Almqvist, Catarina
  • Nordenskjöld, Agneta
  • Nordenström, Anna
subjects:
  • Abridged Index Medicus
  • Adolescent
  • Adrenal Hyperplasia, Congenital - epidemiology
  • Adrenal Hyperplasia, Congenital - genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases - epidemiology
  • Cardiovascular Diseases - genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • endocrine system diseases
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • MEDICAL AND HEALTH SCIENCES
  • MEDICIN OCH HÄLSOVETENSKAP
  • Metabolic Diseases - epidemiology
  • Metabolic Diseases - genetics
  • Middle Aged
  • Neonatal Screening
  • Prevalence
  • Risk
  • Steroid 21-Hydroxylase - genetics
  • Young Adult
ispartof: Journal of Clinical Endocrinology and Metabolism, 2015-09, Vol.100 (9), p.3520-3528
description: Context: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. Objective: This study aimed to study cardiovascular and metabolic morbidity in CAH. Design, Setting, and Participants: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. Main Outcome Measures: To study cardiovascular and metabolic morbidity in CAH. Results: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1–5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9–3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. Conclusions: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
language: eng
source:
identifier: ISSN: 0021-972X
fulltext: no_fulltext
issn:
  • 0021-972X
  • 1945-7197
  • 1945-7197
url: Link


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titleIncreased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study
creatorFalhammar, Henrik ; Frisén, Louise ; Hirschberg, Angelica Linden ; Norrby, Christina ; Almqvist, Catarina ; Nordenskjöld, Agneta ; Nordenström, Anna
creatorcontribFalhammar, Henrik ; Frisén, Louise ; Hirschberg, Angelica Linden ; Norrby, Christina ; Almqvist, Catarina ; Nordenskjöld, Agneta ; Nordenström, Anna ; Karolinska Institutet ; Dept of Medical Epidemiology and Biostatistics ; Inst för medicinsk epidemiologi och biostatistik
descriptionContext: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. Objective: This study aimed to study cardiovascular and metabolic morbidity in CAH. Design, Setting, and Participants: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. Main Outcome Measures: To study cardiovascular and metabolic morbidity in CAH. Results: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1–5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9–3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. Conclusions: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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subjectAbridged Index Medicus ; Adolescent ; Adrenal Hyperplasia, Congenital - epidemiology ; Adrenal Hyperplasia, Congenital - genetics ; Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Child ; Child, Preschool ; Cohort Studies ; endocrine system diseases ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; MEDICAL AND HEALTH SCIENCES ; MEDICIN OCH HÄLSOVETENSKAP ; Metabolic Diseases - epidemiology ; Metabolic Diseases - genetics ; Middle Aged ; Neonatal Screening ; Prevalence ; Risk ; Steroid 21-Hydroxylase - genetics ; Young Adult
ispartofJournal of Clinical Endocrinology and Metabolism, 2015-09, Vol.100 (9), p.3520-3528
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0Falhammar, Henrik
1Frisén, Louise
2Hirschberg, Angelica Linden
3Norrby, Christina
4Almqvist, Catarina
5Nordenskjöld, Agneta
6Nordenström, Anna
7Karolinska Institutet
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9Inst för medicinsk epidemiologi och biostatistik
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0Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study
1Journal of Clinical Endocrinology and Metabolism
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descriptionContext: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. Objective: This study aimed to study cardiovascular and metabolic morbidity in CAH. Design, Setting, and Participants: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. Main Outcome Measures: To study cardiovascular and metabolic morbidity in CAH. Results: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1–5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9–3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. Conclusions: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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1Adolescent
2Adrenal Hyperplasia, Congenital - epidemiology
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6Aged, 80 and over
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18Male
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20MEDICIN OCH HÄLSOVETENSKAP
21Metabolic Diseases - epidemiology
22Metabolic Diseases - genetics
23Middle Aged
24Neonatal Screening
25Prevalence
26Risk
27Steroid 21-Hydroxylase - genetics
28Young Adult
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titleIncreased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study
authorFalhammar, Henrik ; Frisén, Louise ; Hirschberg, Angelica Linden ; Norrby, Christina ; Almqvist, Catarina ; Nordenskjöld, Agneta ; Nordenström, Anna
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1Adolescent
2Adrenal Hyperplasia, Congenital - epidemiology
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6Aged, 80 and over
7Cardiovascular Diseases - epidemiology
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22Metabolic Diseases - genetics
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24Neonatal Screening
25Prevalence
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notesThis work was supported by grants from the Magn. Bergvalls Foundation, Karolinska Institutet, Stockholm County Council, and the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework Grant No. 340-2013-5867.
abstractContext: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. Objective: This study aimed to study cardiovascular and metabolic morbidity in CAH. Design, Setting, and Participants: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. Main Outcome Measures: To study cardiovascular and metabolic morbidity in CAH. Results: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1–5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9–3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. Conclusions: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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pmid26126207
doi10.1210/JC.2015-2093
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