TY - JOUR
T1 - A detailed family history of myocardial infarction and risk of myocardial infarction
T2 - a nationwide cohort study
AU - Ranthe, Mattis Flyvholm
AU - Petersen, Jonathan Aavang
AU - Bundgård, Henning
AU - Wohlfahrt, Jan
AU - Melbye, Mads
AU - Boyd, Heather A
PY - 2015/5
Y1 - 2015/5
N2 - BACKGROUND: Family history of myocardial infarction (MI) is an independent risk factor for MI. Several genetic variants are associated with increased risk of MI and family history of MI in a first-degree relative doubles MI risk. However, although family history of MI is not a simple dichotomous risk factor, the impact of specific, detailed family histories has not received much attention, despite its high clinical relevance. We examined risk of MI by MIs in first- and second-degree relatives and by number and age of affected relatives.METHODS AND FINDINGS: Using Danish national registers, we established a nationwide cohort of persons born between 1930 and 1992 with identifiable first- or second-degree relatives. Incident MIs in both cohort members and relatives aged ≥20 years were identified. We calculated incidence rate ratios (IRRs) for MI by family history of MI, by Poisson regression. In 4.4 million persons followed for 104 million person-years, we identified 128,384 incident MIs. IRRs with 95% confidence intervals [CIs] for MI by history of MI in 1, 2 or ≥3 first-degree relatives were 1.46 (1.42-1.49), 2.38 (2.22-2.56) and 3.58 (2.66-4.81), respectively. Corresponding estimates for second-degree relatives were 1.17 (1.05-1.30), 1.87 (1.46-2.38) and 2.18 (1.09-4.36). A history of MI in combinations of first- and second-degree relatives increased risks 1.8- to 7-fold in middle-aged persons (36 to 55 years). Estimates were robust to adjustment for diabetes, hypertension, dyslipidemia and use of cardiovascular medications.CONCLUSION: A detailed family history, particularly number of affected first- and second-degree relatives, contributes meaningfully to risk assessment, especially in middle-aged persons. Future studies should test for potential improvement of risk algorithm prediction using detailed family histories.
AB - BACKGROUND: Family history of myocardial infarction (MI) is an independent risk factor for MI. Several genetic variants are associated with increased risk of MI and family history of MI in a first-degree relative doubles MI risk. However, although family history of MI is not a simple dichotomous risk factor, the impact of specific, detailed family histories has not received much attention, despite its high clinical relevance. We examined risk of MI by MIs in first- and second-degree relatives and by number and age of affected relatives.METHODS AND FINDINGS: Using Danish national registers, we established a nationwide cohort of persons born between 1930 and 1992 with identifiable first- or second-degree relatives. Incident MIs in both cohort members and relatives aged ≥20 years were identified. We calculated incidence rate ratios (IRRs) for MI by family history of MI, by Poisson regression. In 4.4 million persons followed for 104 million person-years, we identified 128,384 incident MIs. IRRs with 95% confidence intervals [CIs] for MI by history of MI in 1, 2 or ≥3 first-degree relatives were 1.46 (1.42-1.49), 2.38 (2.22-2.56) and 3.58 (2.66-4.81), respectively. Corresponding estimates for second-degree relatives were 1.17 (1.05-1.30), 1.87 (1.46-2.38) and 2.18 (1.09-4.36). A history of MI in combinations of first- and second-degree relatives increased risks 1.8- to 7-fold in middle-aged persons (36 to 55 years). Estimates were robust to adjustment for diabetes, hypertension, dyslipidemia and use of cardiovascular medications.CONCLUSION: A detailed family history, particularly number of affected first- and second-degree relatives, contributes meaningfully to risk assessment, especially in middle-aged persons. Future studies should test for potential improvement of risk algorithm prediction using detailed family histories.
KW - Adult
KW - Cohort Studies
KW - Denmark
KW - Diabetes Mellitus
KW - Family
KW - Female
KW - Humans
KW - Hypertension
KW - Male
KW - Middle Aged
KW - Myocardial Infarction
KW - Risk Factors
U2 - 10.1371/journal.pone.0125896
DO - 10.1371/journal.pone.0125896
M3 - Journal article
C2 - 26011129
SN - 1932-6203
VL - 10
SP - 1
EP - 11
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 5
M1 - e0125896
ER -