2300
JACC VOL. 64, NO. 21, 2014
Letters
DECEMBER 2, 2014:2299–303
*CHU Hôtel Dieu
A
UMR PhAN-HNB1 1 Place Alexis Ricordeau 44000 Nantes France E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2014.07.995
B
Please note: This work was funded by an Investigator Initiated Study Concept Research Grant from Sanofi-Regeneron attributed jointly to Drs. Lambert and Marais, and by the Agence Nationale de la Recherche (Programme blanc BCNCT) to Dr. Lambert. Dr. Lambert has received honoraria and research funding from Sanofi-Regeneron and Pfizer, as well as honoraria from Amgen. Dr. Schwahn is an employee of and owns stock in Sanofi. Dr. Gusarova is an employee of and owns stock in Regeneron. Dr. Blom has received honoraria and clinical trial funding from Sanofi-Regeneron; serves on the advisory board of Amgen, Aegerion, Sanofi, AstraZeneca, and MSD; and has received speakers honoraria from Aegerion, Amgen, AstraZeneca, MSD, Unilever, and Novartis. Dr. Sasiela is an employee of Regeneron. Dr. Marais has research support from SanofiRegeneron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
C
REFERENCES
D
1. Stein EA, Raal F. Reduction of low-density lipoprotein cholesterol by monoclonal antibody inhibition of PCSK9. Annu Rev Med 2014;65:417–31. 2. Hobbs HH, Russell DW, Brown MS, Goldstein JL. The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu Rev Genet 1990;24:133–70.
F I G U R E 1 Alirocumab Restores Maximal LDLR Cell Surface Expression Levels in Non-
FH, HeFH and Receptor Defective HoFH
Control fibroblasts (A), heterozygous familial hypercholesterolemia (HeFH) fibroblasts (B), receptor-defective HoFH fibroblasts (C), and receptor-negative homozygous familial hypercholesterolemia (HoFH) fibroblasts (D) were grown in 20% FCS or 0.5% FCS with increasing concentrations of mevastatin for 24 h. Fibroblasts grown in 0.5% FCS and 40 mg/ml of mevastatin were subsequently treated with
3. Lambert G, Petrides F, Chatelais M, et al. Elevated plasma PCSK9 is equally detrimental for non-familial hypercholesterolemic (non-FH) and heterozygous FH patients, irrespective of their LDL receptor defects. J Am Coll Cardiol 2014; 63:2365–73. 4. Stein EA, Honarpour N, Wasserman SM, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013;128:2113–20.
The Global Cardiovascular Crisis
increasing doses of wild-type rPCSK9 (0 to 6,000 ng/ml) or rPCSK9-D374Y (0 to 600 ng/ml) for 4 h with or without increasing doses of alirocumab (0 to
Glove Up
19,200 ng/ml). LDLR cell surface expression was assessed by flow cytometry (3). *p < 0.01 versus 0.5% FCS. **p < 0.001 versus 0.5% FCSþ 40 mg/ml
I read with great interest the editorial by Fuster
mevastatin. ***p < 0.01 versus 0.5% FCSþ 40 mg/ml mevastatin þ 6,000 ng/ml
(1), detailing both expanded recommendations to
rPCSK9 wild type/600 ng/ml rPCSK9-D374Y. Histograms represent the mean SEM of at least 4 independent experiments. Representative fluorescence charts are displayed. FCS ¼ fetal calf serum; FH ¼ familial hypercholesterolemia;
address the global burden of cardiovascular disease and
the
necessity
for
evaluating
implemented
LDLR ¼ low-density lipoprotein receptor; PCSK9 ¼ proprotein convertase subtilisin
recommendations by measuring outcomes. These are
kexin type 9.
important steps to address a crisis unappreciated by the majority of U.S.-based cardiologists. However, the American College of Cardiology (ACC) and its members can do more to address current needs. *Gilles Lambert, PhD Mathias Chatelais, BSc Francine Petrides, BSc Maxime Passard, BSc Aurélie Thedrez, PhD Kerry-Anne Rye, PhD Uwe Schwahn, PhD Viktoria Gusarova, PhD Dirk J. Blom, MD, PhD William Sasiela, PhD A. David Marais, MD
Cardiovascular disease in the developing world is as much a disease of poverty as newfound affluence. Carbohydrates are cheap and available. Local agriculture is more climate dependent than in the United States and the cost of modern farming practices limits production. Knowledge of a heart healthy diet and the acquisition of that diet are wholly separate. Epidemiologic
assessments
and
disease
prevention
incompletely addresses existing clinical needs. The treatment of disease at the local level could be augmented by cardiologists from the developed world
JACC VOL. 64, NO. 21, 2014
Letters
DECEMBER 2, 2014:2299–303
providing their time, expertise, and interest. There
therefore
will never be enough local physicians to provide these
agree with the authors’ conclusions supporting the
services due to both emigration and the overwhelming
clinical safety of computed tomography (CT) scans
state of third world general medical care. Groups such
in patients with these devices, we have observed
as doc2doc and Pacemaker International are but 2 ex-
several cases of CT-induced arrhythmia during
amples of small groups making a difference.
gated cardiac examinations in patients with rhythm
non-ECG-gated)
studies.
Although
we
The ACC can be a source for regions or commu-
management devices. The resultant arrhythmias
nities seeking advanced cardiovascular care. It can
rendered the examinations non-diagnostic, thus
identify members with an interest in providing
exposing patients to unnecessary radiation.
volunteer services in a tangible, sustainable, and local
Our observed cases involved apparent ventricular
manner. An ACC committee on International Volun-
oversensing, which led to pacemaker suppression,
teer Cardiology comprising physicians with volunteer
causing brief periods of ventricular asystole (Figure 1).
experience might address feasibility concerns and
These occurred while the CT beam was directly
individualize a response team based on local needs
in line with the pacemaker generator. As suggested
and available members. Can services such as pace-
by Hussein et al. (and others) (2,3) the effects were
maker insertion, peripheral revascularization for limb
transient, lasting
JACC VOL. 64, NO. 21, 2014
Letters
DECEMBER 2, 2014:2299–303
*CHU Hôtel Dieu
A
UMR PhAN-HNB1 1 Place Alexis Ricordeau 44000 Nantes France E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2014.07.995
B
Please note: This work was funded by an Investigator Initiated Study Concept Research Grant from Sanofi-Regeneron attributed jointly to Drs. Lambert and Marais, and by the Agence Nationale de la Recherche (Programme blanc BCNCT) to Dr. Lambert. Dr. Lambert has received honoraria and research funding from Sanofi-Regeneron and Pfizer, as well as honoraria from Amgen. Dr. Schwahn is an employee of and owns stock in Sanofi. Dr. Gusarova is an employee of and owns stock in Regeneron. Dr. Blom has received honoraria and clinical trial funding from Sanofi-Regeneron; serves on the advisory board of Amgen, Aegerion, Sanofi, AstraZeneca, and MSD; and has received speakers honoraria from Aegerion, Amgen, AstraZeneca, MSD, Unilever, and Novartis. Dr. Sasiela is an employee of Regeneron. Dr. Marais has research support from SanofiRegeneron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
C
REFERENCES
D
1. Stein EA, Raal F. Reduction of low-density lipoprotein cholesterol by monoclonal antibody inhibition of PCSK9. Annu Rev Med 2014;65:417–31. 2. Hobbs HH, Russell DW, Brown MS, Goldstein JL. The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein. Annu Rev Genet 1990;24:133–70.
F I G U R E 1 Alirocumab Restores Maximal LDLR Cell Surface Expression Levels in Non-
FH, HeFH and Receptor Defective HoFH
Control fibroblasts (A), heterozygous familial hypercholesterolemia (HeFH) fibroblasts (B), receptor-defective HoFH fibroblasts (C), and receptor-negative homozygous familial hypercholesterolemia (HoFH) fibroblasts (D) were grown in 20% FCS or 0.5% FCS with increasing concentrations of mevastatin for 24 h. Fibroblasts grown in 0.5% FCS and 40 mg/ml of mevastatin were subsequently treated with
3. Lambert G, Petrides F, Chatelais M, et al. Elevated plasma PCSK9 is equally detrimental for non-familial hypercholesterolemic (non-FH) and heterozygous FH patients, irrespective of their LDL receptor defects. J Am Coll Cardiol 2014; 63:2365–73. 4. Stein EA, Honarpour N, Wasserman SM, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013;128:2113–20.
The Global Cardiovascular Crisis
increasing doses of wild-type rPCSK9 (0 to 6,000 ng/ml) or rPCSK9-D374Y (0 to 600 ng/ml) for 4 h with or without increasing doses of alirocumab (0 to
Glove Up
19,200 ng/ml). LDLR cell surface expression was assessed by flow cytometry (3). *p < 0.01 versus 0.5% FCS. **p < 0.001 versus 0.5% FCSþ 40 mg/ml
I read with great interest the editorial by Fuster
mevastatin. ***p < 0.01 versus 0.5% FCSþ 40 mg/ml mevastatin þ 6,000 ng/ml
(1), detailing both expanded recommendations to
rPCSK9 wild type/600 ng/ml rPCSK9-D374Y. Histograms represent the mean SEM of at least 4 independent experiments. Representative fluorescence charts are displayed. FCS ¼ fetal calf serum; FH ¼ familial hypercholesterolemia;
address the global burden of cardiovascular disease and
the
necessity
for
evaluating
implemented
LDLR ¼ low-density lipoprotein receptor; PCSK9 ¼ proprotein convertase subtilisin
recommendations by measuring outcomes. These are
kexin type 9.
important steps to address a crisis unappreciated by the majority of U.S.-based cardiologists. However, the American College of Cardiology (ACC) and its members can do more to address current needs. *Gilles Lambert, PhD Mathias Chatelais, BSc Francine Petrides, BSc Maxime Passard, BSc Aurélie Thedrez, PhD Kerry-Anne Rye, PhD Uwe Schwahn, PhD Viktoria Gusarova, PhD Dirk J. Blom, MD, PhD William Sasiela, PhD A. David Marais, MD
Cardiovascular disease in the developing world is as much a disease of poverty as newfound affluence. Carbohydrates are cheap and available. Local agriculture is more climate dependent than in the United States and the cost of modern farming practices limits production. Knowledge of a heart healthy diet and the acquisition of that diet are wholly separate. Epidemiologic
assessments
and
disease
prevention
incompletely addresses existing clinical needs. The treatment of disease at the local level could be augmented by cardiologists from the developed world
JACC VOL. 64, NO. 21, 2014
Letters
DECEMBER 2, 2014:2299–303
providing their time, expertise, and interest. There
therefore
will never be enough local physicians to provide these
agree with the authors’ conclusions supporting the
services due to both emigration and the overwhelming
clinical safety of computed tomography (CT) scans
state of third world general medical care. Groups such
in patients with these devices, we have observed
as doc2doc and Pacemaker International are but 2 ex-
several cases of CT-induced arrhythmia during
amples of small groups making a difference.
gated cardiac examinations in patients with rhythm
non-ECG-gated)
studies.
Although
we
The ACC can be a source for regions or commu-
management devices. The resultant arrhythmias
nities seeking advanced cardiovascular care. It can
rendered the examinations non-diagnostic, thus
identify members with an interest in providing
exposing patients to unnecessary radiation.
volunteer services in a tangible, sustainable, and local
Our observed cases involved apparent ventricular
manner. An ACC committee on International Volun-
oversensing, which led to pacemaker suppression,
teer Cardiology comprising physicians with volunteer
causing brief periods of ventricular asystole (Figure 1).
experience might address feasibility concerns and
These occurred while the CT beam was directly
individualize a response team based on local needs
in line with the pacemaker generator. As suggested
and available members. Can services such as pace-
by Hussein et al. (and others) (2,3) the effects were
maker insertion, peripheral revascularization for limb
transient, lasting
