To the Editor
Sir,
The excellent article by Oliver-Williams and co-authors (1) provides
strong evidence to link miscarriages, the most prevalent major
complication of pregnancy, the commonest situation in women's life, with
coronary heart disease (CHD), the leading cause of death in women.
The relationship between miscarriage and cardiovascular risk should
be attributed to certain risk factors shared by the two multifactorial
disorders, thrombophilia holding a prominent position. Acquired
thrombophilia is adequately discussed in the article. Recent attention has
been focused on inherited thrombophilic factors that may predispose to
pregnancy complications, including pregnancy loss. The genetic
heterogeneity of several loci, including coagulation factors V (FVL-R506Q)
and II (FII-G20210A), strongly associated with venous and modestly with
arterial thrombosis (2), and platelet glycoproteins Ia (GpIa-C807T) and
IIIa (GpIIIa-PlA1/PlA2) which influence thrombosis exclusively in the
arterial side, have been studied in women with miscarriages (3).
Clinically significant relative risks are mainly related to the
accumulation of risk alleles acting synergistically (4). The postulated
pathogenetic mechanisms include abnormal placentation and reduced
perfusion of the intervillous space.
Albeit the majority of miscarriages are considered to be sporadic,
the important corollary of this study is that women with a history of even
one miscarriage are at 50% higher risk of CHD. The authors also report a
twofold risk for women with recurrent miscarriages, implying a "dose-
response relationship". However, some women may have experienced only one
fetal loss because they had only one pregnancy, but still have a higher
burden of risk factors, compared with those with recurrent miscarriages.
High-risk women would be expected to have an increased incidence of
miscarriages in younger age (age is an established risk factor for
miscarriage) or miscarry earlier in pregnancy (3) (the accumulation of
risk factors contributing to an acceleration of the biological processes
of the disorder). A potential explanation of the aforementioned finding
could be that every fetal loss per se increases cardiovascular risk,
potentially via endothelial stimulation or dysfunction, hence these women
should be considered for relevant evaluation (e.g. FDA approved
Lipoprotein-associated phospholipase A2 and/or flow mediated dilatation).
These results support respective screening in women with at least one
miscarriage to identify individual risk factors in order to provide
personalized treatment for successful completion of next pregnancy and
early prevention of future cardiovascular events
Nikolaos Vlachadis M.D.(1),
Vassileios Tsamadias B.Sc.(1),
Emmanouel Economou Ph.D.(2)
(1) Research Fellow
(2) Assistant Professor of Pharmacogenetics
Clinical Laboratory of Therapeutic Individualization,
Second Department of Obstetrics and Gynaecology,
National and kapodistrian University of Athens, Medical School, Aretaieio
Hospital,
76 Vasilissis Sofias Avenue, 115 28, Athens, Greece
References
1)Oliver-Williams CT, Heydon EE, Smith GC, Wood AM. Miscarriage and
future maternal cardiovascular disease: a systematic review and meta-
analysis. Heart. 2013 Mar 28. [Epub ahead of print] doi:10.1136/heartjnl-
2012-303237
2)de Moerloose P, Boehlen F. Inherited thrombophilia in arterial
disease: a selective review. Semin Hematol. 2007;44:106-113
3)Gerhardt A, Scharf RE, Mikat-Drozdzynski B, Kr?ssel JS, Bender HG,
Zotz RB. The polymorphism of platelet membrane integrin alpha2beta1
(alpha2807TT) is associated with premature onset of fetal loss. Thromb
Haemost. 2005;93:124-9.
4)Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple
thrombophilic gene mutations rather than specific gene mutations are risk
factors for recurrent miscarriage. Am J Reprod Immunol. 2006;55:360-368.
Conflict of Interest:
None declared
To the Editor
Sir,
The excellent article by Oliver-Williams and co-authors (1) provides strong evidence to link miscarriages, the most prevalent major complication of pregnancy, the commonest situation in women's life, with coronary heart disease (CHD), the leading cause of death in women.
The relationship between miscarriage and cardiovascular risk should be attributed to certain risk factors shared by the two multifactorial disorders, thrombophilia holding a prominent position. Acquired thrombophilia is adequately discussed in the article. Recent attention has been focused on inherited thrombophilic factors that may predispose to pregnancy complications, including pregnancy loss. The genetic heterogeneity of several loci, including coagulation factors V (FVL-R506Q) and II (FII-G20210A), strongly associated with venous and modestly with arterial thrombosis (2), and platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa-PlA1/PlA2) which influence thrombosis exclusively in the arterial side, have been studied in women with miscarriages (3). Clinically significant relative risks are mainly related to the accumulation of risk alleles acting synergistically (4). The postulated pathogenetic mechanisms include abnormal placentation and reduced perfusion of the intervillous space.
Albeit the majority of miscarriages are considered to be sporadic, the important corollary of this study is that women with a history of even one miscarriage are at 50% higher risk of CHD. The authors also report a twofold risk for women with recurrent miscarriages, implying a "dose- response relationship". However, some women may have experienced only one fetal loss because they had only one pregnancy, but still have a higher burden of risk factors, compared with those with recurrent miscarriages. High-risk women would be expected to have an increased incidence of miscarriages in younger age (age is an established risk factor for miscarriage) or miscarry earlier in pregnancy (3) (the accumulation of risk factors contributing to an acceleration of the biological processes of the disorder). A potential explanation of the aforementioned finding could be that every fetal loss per se increases cardiovascular risk, potentially via endothelial stimulation or dysfunction, hence these women should be considered for relevant evaluation (e.g. FDA approved Lipoprotein-associated phospholipase A2 and/or flow mediated dilatation).
These results support respective screening in women with at least one miscarriage to identify individual risk factors in order to provide personalized treatment for successful completion of next pregnancy and early prevention of future cardiovascular events
Nikolaos Vlachadis M.D.(1),
Vassileios Tsamadias B.Sc.(1),
Emmanouel Economou Ph.D.(2)
(1) Research Fellow
(2) Assistant Professor of Pharmacogenetics
Clinical Laboratory of Therapeutic Individualization, Second Department of Obstetrics and Gynaecology, National and kapodistrian University of Athens, Medical School, Aretaieio Hospital, 76 Vasilissis Sofias Avenue, 115 28, Athens, Greece
References
1)Oliver-Williams CT, Heydon EE, Smith GC, Wood AM. Miscarriage and future maternal cardiovascular disease: a systematic review and meta- analysis. Heart. 2013 Mar 28. [Epub ahead of print] doi:10.1136/heartjnl- 2012-303237
2)de Moerloose P, Boehlen F. Inherited thrombophilia in arterial disease: a selective review. Semin Hematol. 2007;44:106-113
3)Gerhardt A, Scharf RE, Mikat-Drozdzynski B, Kr?ssel JS, Bender HG, Zotz RB. The polymorphism of platelet membrane integrin alpha2beta1 (alpha2807TT) is associated with premature onset of fetal loss. Thromb Haemost. 2005;93:124-9.
4)Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol. 2006;55:360-368.
Conflict of Interest:
None declared