- Email: [email protected]
Identifying familial hypercholesterolemia in Colombia
Accepted Manuscript Identifying Familial Hypercholesterolemia in Colombia Juan Manuel Toro, Alejandro Román-González, Carlos Alfonso Builes-Barrera PII:
S1933-2874(17)30334-3
DOI:
10.1016/j.jacl.2017.05.008
Reference:
JACL 1120
To appear in:
Journal of Clinical Lipidology
Received Date: 16 May 2017 Revised Date:
23 May 2017
Accepted Date: 23 May 2017
Please cite this article as: Toro JM, Román-González A, Builes-Barrera CA, Identifying Familial Hypercholesterolemia in Colombia, Journal of Clinical Lipidology (2017), doi: 10.1016/j.jacl.2017.05.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Identifying Familial Hypercholesterolemia in Colombia
RI PT
Running Title: Familial Hypercholesterolemia in Colombia Authors:
Juan Manuel Toro1, Alejandro Román-González2, Carlos Alfonso Builes-Barrera2,3 Affiliations
SC
1- Department of Internal Medicine. Hospital Pablo Tobon Uribe. Calle 78b #69-240. Medellin, Colombia.
M AN U
2- Professor of Endocrinólogy. Department of Internal Medicine. Universidad de Antioquia. Hospital Universitario San Vicente Fundación. Medellin, Colombia 3- Laboratorio Dinámica IPS. Medellin, Colombia
Authors:
1. Given Name: Juan Manuel Family name: Toro1 E-mail: [email protected]
TE D
2. Given Name: Carlos Alfonso Family name: Builes-Barrera2,3 E-mail: [email protected]
EP
3. Given Name: Alejandro Family name: Román-González2,4* Email: [email protected]
*Correspondence:
AC C
Dr. Alejandro Román-González Email: [email protected] Address:
Calle 64 No 51d-154
Oficina Endocrinología y Diabetes Hospital Universitario San Vicente Fundación Medellin, Colombia Phone number 2635397
ACCEPTED MANUSCRIPT 2
Dear editor, Clinical practice guidelines recommend the use of high-dose statin therapy for patients with
RI PT
low density lipoprotein cholesterol concentrations (LDL-C) higher than 190 mg/dL. Some patients with this LDL concentration may have familial hypercholesterolemia (FH). Additionally, the Dutch Lipid Clinic Network provides point-based diagnostic criteria that are based on an increasing LDL-C, physical exam, and personal and familial history of
SC
elevated LDL-C, the last of which is the most important diagnostic feature. Knowing the
M AN U
probability of a genetic cause should help in deciding to do cascade screening among the relatives of the patient with such elevated cholesterol. We recently read the article by Santos et al published in this journal(1), who stated that the data regarding the prevalence of FH Colombian data was not adequate. We would like to share some of the data that we
Methods:
TE D
are collecting in an attempt to address this issue in our country.
All lipid profiles performed in people older than 18 years during 2015 at the Laboratorio
EP
Dinámica IPS, Medellin, Colombia were collected. Only the first sample from repeated lipid profiles was included for each patient. Lipid profiles with triglycerides higher than
AC C
400 mg/dL were excluded. LDL was calculated using the Friedewald formula. The total cholesterol and triglyceride concentrations were measured by colorimetric enzymatic test with a Cobas 701 (Roche) and the HDL cholesterol was measured with a Cobas 502 (Roche)
Results:
ACCEPTED MANUSCRIPT 3
Overall, 189855 lipid profiles were included; 60% were female, and the median age was 52 years (18-105). The mean LDL was 115.1 mg/dL (25-535 mg/dL), and the 25-75 percentile
found, and 63 samples had LDL-C ≥ 300 mg/dL (0.03%).
RI PT
range was 90-137.6 mg/dL. Further, 5685 (3%) LDL-C measurements ≥ 190 mg/dL were
If we assume that 1 out of 5 patients with LDL-C >190 mg/dL may have FH(2), the estimated prevalence of FH could be 0.6% or 1/167 patients acquired in this manner.
SC
Applying these estimates to the general population over 18 years of age in Medellin during 2015, (N = 1´912.119), and the estimated population over 18 years of age in Colombia (N =
M AN U
32´737.024(3), the estimated number of FH cases could be approximately 11473 in Medellin and 196422 in Colombia. The number of cases of FH is concordant with the proposed number of FH cases in Colombia (96000 to 240000 cases)(4). We hope that this letter will help in our making further decisions regarding important
TE D
prevalence studies and in planning for adequate medical care for such patients who have been largely forgotten in our country. Currently, there are no systematic efforts to identify these patients and their affected family members or to provide molecular diagnostic
EP
programs for FH in our country. The Ibero-American FH (IBAFH) network (1) represents
AC C
an opportunity to close the gap in FH diagnosis, treatment, awareness and education in our region. Clearly, more data are needed (5). Declaration of interest:
Dr. Roman-Gonzalez, MD, has received speaker’s fees from Sanofi, Amgen, Novo Nordisk and Novartis. Dr. Builes-Barrera, MD has received speaker’s fees from Sanofi and Merck.
ACCEPTED MANUSCRIPT 4
Dr. Toro, MD has received speaker’s fees from Amgen.
This work has been funded by Dinámica IPS References
2.
SC
Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, Merchan A, Alves AC, Medeiros AM, Jannes CE, Krieger JE, Schreier L, Perez de Isla L, Magaña-Torres MT, Stoll M, Mata N, Dell Oca N, Corral P, Asenjo S, Bañares VG, Reyes X, Mata P, Network I-AFH. 2017. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol 11(1):160-166. Lahtinen AM, Havulinna AS, Jula A, Salomaa V, Kontula K. 2015. Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population. Atherosclerosis 238(1):64-69.
M AN U
1.
3.
TE D
EP
5.
https://www.dane.gov.co/files/investigaciones/poblacion/proyepobla06_20/ VisorCertificaPPO_Oct11.xls. Merchán A, Ruiz ÁJ, Campo R, Prada CE, Toro JM, Sánchez R, Gómez JE, Jaramillo NI, Molina DI, Vargas-Uricoechea H, Sixto S, Castro JM, Quintero AE, Coll M, Slotkus S, Ramírez A, Pachajoa H, Ávila FA, Alonso K R. 2016. Hipercolesterolemia familiar: artículo de revisión. Revista Colombiana de Cardiología 23:4-26. Mehta R, Zubirán R, Martagón AJ, Vazquez-Cárdenas A, Segura-Kato Y, TusiéLuna MT, Aguilar-Salinas CA. 2016. The panorama of familial hypercholesterolemia in Latin America: a systematic review. J Lipid Res 57(12):2115-2129.
AC C
4.
RI PT
Acknowledgements:
S1933-2874(17)30334-3
DOI:
10.1016/j.jacl.2017.05.008
Reference:
JACL 1120
To appear in:
Journal of Clinical Lipidology
Received Date: 16 May 2017 Revised Date:
23 May 2017
Accepted Date: 23 May 2017
Please cite this article as: Toro JM, Román-González A, Builes-Barrera CA, Identifying Familial Hypercholesterolemia in Colombia, Journal of Clinical Lipidology (2017), doi: 10.1016/j.jacl.2017.05.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Identifying Familial Hypercholesterolemia in Colombia
RI PT
Running Title: Familial Hypercholesterolemia in Colombia Authors:
Juan Manuel Toro1, Alejandro Román-González2, Carlos Alfonso Builes-Barrera2,3 Affiliations
SC
1- Department of Internal Medicine. Hospital Pablo Tobon Uribe. Calle 78b #69-240. Medellin, Colombia.
M AN U
2- Professor of Endocrinólogy. Department of Internal Medicine. Universidad de Antioquia. Hospital Universitario San Vicente Fundación. Medellin, Colombia 3- Laboratorio Dinámica IPS. Medellin, Colombia
Authors:
1. Given Name: Juan Manuel Family name: Toro1 E-mail: [email protected]
TE D
2. Given Name: Carlos Alfonso Family name: Builes-Barrera2,3 E-mail: [email protected]
EP
3. Given Name: Alejandro Family name: Román-González2,4* Email: [email protected]
*Correspondence:
AC C
Dr. Alejandro Román-González Email: [email protected] Address:
Calle 64 No 51d-154
Oficina Endocrinología y Diabetes Hospital Universitario San Vicente Fundación Medellin, Colombia Phone number 2635397
ACCEPTED MANUSCRIPT 2
Dear editor, Clinical practice guidelines recommend the use of high-dose statin therapy for patients with
RI PT
low density lipoprotein cholesterol concentrations (LDL-C) higher than 190 mg/dL. Some patients with this LDL concentration may have familial hypercholesterolemia (FH). Additionally, the Dutch Lipid Clinic Network provides point-based diagnostic criteria that are based on an increasing LDL-C, physical exam, and personal and familial history of
SC
elevated LDL-C, the last of which is the most important diagnostic feature. Knowing the
M AN U
probability of a genetic cause should help in deciding to do cascade screening among the relatives of the patient with such elevated cholesterol. We recently read the article by Santos et al published in this journal(1), who stated that the data regarding the prevalence of FH Colombian data was not adequate. We would like to share some of the data that we
Methods:
TE D
are collecting in an attempt to address this issue in our country.
All lipid profiles performed in people older than 18 years during 2015 at the Laboratorio
EP
Dinámica IPS, Medellin, Colombia were collected. Only the first sample from repeated lipid profiles was included for each patient. Lipid profiles with triglycerides higher than
AC C
400 mg/dL were excluded. LDL was calculated using the Friedewald formula. The total cholesterol and triglyceride concentrations were measured by colorimetric enzymatic test with a Cobas 701 (Roche) and the HDL cholesterol was measured with a Cobas 502 (Roche)
Results:
ACCEPTED MANUSCRIPT 3
Overall, 189855 lipid profiles were included; 60% were female, and the median age was 52 years (18-105). The mean LDL was 115.1 mg/dL (25-535 mg/dL), and the 25-75 percentile
found, and 63 samples had LDL-C ≥ 300 mg/dL (0.03%).
RI PT
range was 90-137.6 mg/dL. Further, 5685 (3%) LDL-C measurements ≥ 190 mg/dL were
If we assume that 1 out of 5 patients with LDL-C >190 mg/dL may have FH(2), the estimated prevalence of FH could be 0.6% or 1/167 patients acquired in this manner.
SC
Applying these estimates to the general population over 18 years of age in Medellin during 2015, (N = 1´912.119), and the estimated population over 18 years of age in Colombia (N =
M AN U
32´737.024(3), the estimated number of FH cases could be approximately 11473 in Medellin and 196422 in Colombia. The number of cases of FH is concordant with the proposed number of FH cases in Colombia (96000 to 240000 cases)(4). We hope that this letter will help in our making further decisions regarding important
TE D
prevalence studies and in planning for adequate medical care for such patients who have been largely forgotten in our country. Currently, there are no systematic efforts to identify these patients and their affected family members or to provide molecular diagnostic
EP
programs for FH in our country. The Ibero-American FH (IBAFH) network (1) represents
AC C
an opportunity to close the gap in FH diagnosis, treatment, awareness and education in our region. Clearly, more data are needed (5). Declaration of interest:
Dr. Roman-Gonzalez, MD, has received speaker’s fees from Sanofi, Amgen, Novo Nordisk and Novartis. Dr. Builes-Barrera, MD has received speaker’s fees from Sanofi and Merck.
ACCEPTED MANUSCRIPT 4
Dr. Toro, MD has received speaker’s fees from Amgen.
This work has been funded by Dinámica IPS References
2.
SC
Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, Merchan A, Alves AC, Medeiros AM, Jannes CE, Krieger JE, Schreier L, Perez de Isla L, Magaña-Torres MT, Stoll M, Mata N, Dell Oca N, Corral P, Asenjo S, Bañares VG, Reyes X, Mata P, Network I-AFH. 2017. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol 11(1):160-166. Lahtinen AM, Havulinna AS, Jula A, Salomaa V, Kontula K. 2015. Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population. Atherosclerosis 238(1):64-69.
M AN U
1.
3.
TE D
EP
5.
https://www.dane.gov.co/files/investigaciones/poblacion/proyepobla06_20/ VisorCertificaPPO_Oct11.xls. Merchán A, Ruiz ÁJ, Campo R, Prada CE, Toro JM, Sánchez R, Gómez JE, Jaramillo NI, Molina DI, Vargas-Uricoechea H, Sixto S, Castro JM, Quintero AE, Coll M, Slotkus S, Ramírez A, Pachajoa H, Ávila FA, Alonso K R. 2016. Hipercolesterolemia familiar: artículo de revisión. Revista Colombiana de Cardiología 23:4-26. Mehta R, Zubirán R, Martagón AJ, Vazquez-Cárdenas A, Segura-Kato Y, TusiéLuna MT, Aguilar-Salinas CA. 2016. The panorama of familial hypercholesterolemia in Latin America: a systematic review. J Lipid Res 57(12):2115-2129.
AC C
4.
RI PT
Acknowledgements: