BRIEF ARTICLE
Severe Hypertriglyceridemia in Argentina: Prevalence and Clinical
Characteristics
Hipertrigliceridemia grave en Argentina: prevalencia y características clínicas
Benjamín Sáenz1,3, María G. Matta1, Facundo Blautzik1, Agustina Corral1, Facundo Sampayo2, Federico Piedrabuena2, Pablo Corral1
1 Universidad FASTA, School
of Medicine, Chair of Special
Pharmacology and Toxicology, Mar del Plata.
2 HIGA Dr. Oscar Alende, Internal Medicine Residency, Mar del Plata
Address for reprints:
Benjamín Sáenz
saenzbenjamin@hotmail.com
Rev Argent Cardiol 2023;91:140-143.
http://dx.doi.org/10.7775/rac.v91.i2.20610
ABSTRACT
Background: Severe hypertriglyceridemia (SHTG) is a metabolic disorder
with multiple origins and management implications. Prevalence, clinical characteristics, and its possible
causes are unknown
in Argentina.
Objective: The aim of this study was to estimate
the prevalence and describe the clinical characteristics and underlying SHTG
causes in a third level hospital in the municipality of General Pueyrredón.
Methods: An observational, descriptive study was performed using an
electronic database from a provincial Hospital. It included adult patients with triglyceride (TG) levels above 885 mg/dL (10 mmol/L) evaluated from January 2018 to December 2021. Medical records were collected, and
patients were then contacted to obtain anthropometric measurements, sociodemographic variables, personal and family history, secondary
causes of hypertriglyceridemia, and treatment received.
Results: Among 16 029 patients
analyzed, 46 presented
SHTG, representing a total prevalence of 0.28% (95% CI 0.20-0.40%). Finally, 19 participants with mean age 48.47±16 years and 84.2%
men were included in the analysis. Median TG level was 1821 mg/dL (interquartile range 917-7000 mg/dL),
and 17 participants (84.97%) had hypercholesterolemia (total cholesterol
>200 mg/dL). Almost 50% reported alcohol consumption, 55% were obese and 68% had
type II diabetes. Nine participants were under pharmacological treatment, 4 with fibrates
and 5 with statins.
Conclusion: A prevalence of 0.28% SHTG was found, higher than that
reported in other series. Another finding was the underuse of medication for this severe dyslipidemia.
Keywords:
Hypertriglyceridemia - Triglycerides - Prevalence - Argentina
RESUMEN
Introducción: La hipertrigliceridemia
grave (HTGG) es un desorden metabólico con múltiples causas e implicancias
terapéuticas. Se desconocen hasta la fecha las características clínicas, la prevalencia y sus posibles
causas en nuestra población.
Objetivo: Estimar la prevalencia, describir
las características clínicas
y causas subyacentes de la HTGG en un hospital de tercer nivel del municipio
de General Pueyrredón.
Materia Y métodos:
Estudio descriptivo y observacional realizado con pacientes ambulatorios e internados de un hospital
provincial. Se incluyeron pacientes adultos con triglicéridos (TG) mayores que 885 mg/dL (10 mmol/L) evaluados desde
enero de 2018 a diciembre de 2021. Se extrajeron
sus historias clínicas y, luego, se los contactó para obtener medidas antropométricas,
variables sociodemográficas, antecedentes personales y familiares, causas secundarias de hipertrigliceridemia y el tratamiento recibido.
Resultados: Se analizaron 16 029 muestras; 46
presentaron HTGG, lo que representa una prevalencia total del 0,28 % (IC 95%
0,20- 0,40%); se incluyeron 19
participantes en el análisis. La edad media fue de 48,47 años (DE ±16); el 84,2
% de ellos eran hombres. La mediana
de triglicéridos fue 1821 mg/dL (rango intercuartílico 917-7000 mg/dL);
17 participantes (84,97 %) presentaban hipercolesterolemia (colesterol total
mayor que 200 mg/dL). Casi el 50 % refirió consumo de
alcohol, el 55 % presentaba obesidad y el 68 %
diabetes tipo II. Solo 9 participantes se encontraban en tratamiento, 4 con fibratos y 5 con estatinas.
Conclusión: Se encontró una prevalencia del 0,28 %, más alta que la esperada y reportada en series previas.
Por otro lado, se destaca
la subutilización de medicación para el tratamiento de esta dislipidemia grave.
Palabras claves: Hipertrigliceridemia -
Triglicéridos - Prevalencia - Argentina
Received: 11/11/2022
Accepted: 02/13/2023
INTRODUCTION
Hypertriglyceridemia (HTG) is defined as an elevation of triglycerides (TG) that exceeds 150 mg/dL (1.7 mmol/L). Several population surveys show that it is the most prevalent
lipid disorder and the NHANES
survey revealed that 24.7% present this disorder in the general population. (1,2) When
classifying the severity of HTG, we define it as mild-moderate (up to 500-885 mg/dL) and severe HTG (SHTG), when it exceeds these cut-off points. (3) SHTG can be secondary to
other pathologies, such as diabetes, alcohol abuse and hypothyroidism; to physiological situations, such as pregnancy; or secondary to drugs, such
as contraceptives and protease inhibitors, as the most frequent ones. (4) Similarly, in a smaller percentage, SHTG is due to monogenic genetic disorders, such
as familial chylomicronemia syndrome
or lipodystrophies, or polygenic disorders, such as multifactorial chylomicronemia syndrome. (5) Once diagnosed, the treatment
goal is to reduce the risk of pancreatitis, a complication directly associated
with the TG level, which in SHTG has an incidence of 20%. (6)
The prevalence of SHTG in Argentina, as well as its
potential causes, is currently unknown. The objective of this study was to
estimate the prevalence of SHTG in a
hospital population (outpatient and inpatient), as well as the characterization
and discrimination of the potential causes of this condition.
METHODS
A descriptive, observational study was carried out using
an electronic database (Plexus) of
patients treated at HIGA Dr. Oscar E.
Alende hospital in Mar del Plata. Medical records were included from January 2018 to
December 2021 and the data was
collected during the month of July 2022 by the research team of the EPAHiTS Project (Argentine Prevalence Study of Severe Hypertriglyceridemia). The
inclusion criteria to participate in this study was to
have a TG level ≥885 mg/dL and age ≥18 years.
Data collection
The clinical history of each of patient with inclusion
criteria was reviewed.
A trained physician
reviewed the clinical history, previous
hospitalizations, and the presence of a history
of acute pancreatitis. Subsequently, all the patients were contacted by telephone and an appointment was made at the hospital
to collect sociodemographic and anthropometric data (weight and height), and establish the medical history
(diabetes, alcohol consumption, presence of hypothyroidism and renal failure).
They were asked about personal
and family history related with HTG: presence of recurrent
abdominal pain, acalculous pancreatitis, family history of dyslipidemia, and treatment received.
Secondary causes were also questioned: poorly controlled diabetes,
hypothyroidism, renal failure,
and pregnancy. Patients
were examined to verify the presence of eruptive xanthomas. Finally,
the last blood
test obtained in the clinical
history was considered for laboratory values:
glycosylated hemoglobin (HbA1c),
total cholesterol, LDL cholesterol (LDL-C), HDL
cholesterol (HDL- C), ultrasensitive thyrotropin, and apolipoprotein B (ApoB). Anthropometric measurements were obtained using standard techniques
and protocols. Weight was measured
in light clothing, without shoes, and in kilograms to one decimal place
using a foot scale. Height was measured in centimeters, without shoes and with only one decimal
place. With these data, the
body mass index (BMI) was calculated dividing
body weight in kilograms by the square of height in meters (BMI = weight [kg]/height2 [m2]). For alcohol consumption, a
structured questionnaire based on the Hispanic
Community Health Study was used adapted for its use in Argentina, (7) in which the type of alcoholic beverage (wine, beer, or both) and number of drinks per
week were differentiated.
Definition of variables
Obesity was defined as the presence of a BMI 30 kg/m2. Alcohol
consumption was classified according to intensity as: no consumption, moderate consumption (up to 7 drinks in women and 14 in men), severe consumption
(8 or more in women or 15 or more in
men) and compulsive consumption. (4
to 5 drinks in 2 hours). Hypercholesterolemia was defined as LDL-C ≥ 200
mg/dL or use of statins. The presence of diabetes was
identified by self-report or previous laboratory tests with fasting
blood glucose ≥126 mg/dL, or use of insulin
or oral antidiabetic agents. Poorly controlled
diabetes was described as the presence
of HbA1c >12%.
Statistical analysis
The frequency and distribution of the variables
was analyzed at a global level. Categorical data are
presented as percentages, and for continuous data, the mean was used for
central tendency and standard
deviation (SD) for dispersion in the case
of normal distribution. For non-normal distribution of continuous data, median for central tendency and interquartile range for dispersion were used as summary measures.
RESULTS
Study participants
The total number of participants analyzed was 16 029. Among them, 46 patients presented SHTG,
representing a total prevalence of 0.28% (95% CI 0.20-0.40%). Finally,
19 patients were contacted and included in the
analysis. (Figure 1) Of the 46 initial patients and the 19 finally analyzed, 10 and 3, respectively, were hospitalized at the time of data
collection. Of the patients not contacted, 2 died. One was a female patient with human immunodeficiency virus (HIV) under treatment
with protease inhibitors, and uncontrolled diabetes
(HbA1c 14.7%) and the cause of death was sepsis due to skin and soft tissue injuries. The second case of
death corresponded to a 42-year-old patient with poorly controlled diabetes
(HbA1c 12.9%), chronic renal failure
secondary to diabetes and SHTG (>3000
mg/dL) in different determinations, who died of diabetic ketoacidosis. Four patients
refused to provide data; in 12, the telephone number did not correspond to what
was registered in the system and the remaining 9 did not present contact
information in the system.
Fig. 1. Flowchart of the patients included in the study.
DM: diabetes mellitus. SHTG: severe hypertriglyceridemia
Baseline characteristics of the 19 participants are presented in Table 1. Mean age was
48.47±16 years, and 84.2% were men.
Median TG level was 1821 mg/ dL (interquartile range 917-7000 mg/dL)
and 17 participants (84.97%) had hypercholesterolemia (total cholesterol >200 mg/dL). Almost 50% reported alcohol consumption; however, all
drinking patterns were classified as
moderate (up to 7 drinks per week for women
and up to 14 for men); 55% presented obesity
and 68% type II diabetes. Only 6 participants (31%) reported
the presence of recurrent and chronic abdominal pain, and 1 case of
pancreatitis was recorded. Nine
participants were on pharmacological treatment, 4 with fibrates
and 5 with statins.
|
Categorical
variables, n (%) |
|
|
Men |
16 (84.21) |
|
Diabetes |
13 (68.42) |
|
Alcohol consumption |
9 (47.37) |
|
History of familial
hypercholesterolemia |
9 (47.37) |
|
History of hypertriglyceridemia |
8 (42.1) |
|
Recurrent abdominal pain |
6 (31.58) |
|
Abdominal pain in childhood |
1 (5.26) |
|
Acalculous pancreatitis |
1 (5.26) |
|
Xanthomas |
0 |
|
Fibrates |
4 (21) |
|
Statins |
5 (26) |
|
Quantitative
variables |
|
|
Age, years (mean ±SD) |
48.47±16 |
|
BMI kg/m2 (median,
IQR) |
31 (21-45) |
|
Glycosylated hemoglobin (mean±SD) |
9.3 ±2.8 |
|
Total cholesterol, mg/dL (median, IQR) |
282 (166-721) |
|
HDL cholesterol, mg/dL (mean±SD) |
31 ±5.8 |
|
Triglycerides, mg/dL (median, IQR) |
1821 (917-7000) |
BMI: body mass index; IQR: Interquartile Range; SD: Standard
Deviation
DISCUSSION
This study
shows that the prevalence of SHTG in a tertiary
level hospital in Argentina is 0.28% (95% CI
0.20-0.40%). This value is at the upper end of the range reported by different series of studies worldwide. The
prevalence described, though low, presents a
great discrepancy and variability according to the region studied. For example, in Japan, Tada et al. described a prevalence of 0.3% SHTG; in Israel, Zafrir
et al., 0.09%; in Norway, Retterstøl et al., 0.13% and in Russia, Karpov reported only 0.037%. (8-11)
In the detailed analysis of our sample, we observed that median BMI was 31, which suggests
an associated underlying metabolic disorder, independently of other comorbidities, and a probable cause
of SHTG. This was reflected in 52%
(10/19) of the patients. On the other
hand, 3 patients had HbA1c >10%, without obesity.
These data are even higher than those reported in the work of Masson et al.,
whose population with SHTG
presented obesity in 38.6% and diabetes only in 28.1% of cases. (12) Regarding the use of drugs with an established association with SHTG, 2 patients used protease inhibitors to control their HIV. (3) Thus, we can confirm
that 79% (15/19)
of the screened patients had a secondary condition as the
potential cause of their SHTG. Two of
the four remaining patients presented a transient
elevation of TG, a situation that may be the consequence of not respecting fasting prior to blood withdrawal, alcohol intake or physical exercise; (3) one of the patients was undergoing tuberculostatic treatment
in maintenance phase with rifampin and isoniazid, a drug that,
according to animal studies, could be related
to SHTG. (13) Finally, the remaining
participant met the criteria for famil ial combined hyperlipidemia, (14) since he presented elevated total cholesterol and
TG in successive blood tests with a
first-degree relative relationship with a similar lipid profile. Regarding the results observed
in terms of underutilization of pharmacological treatment, this finding
is coincident with that reported by the
group of Masson et al., which states that only 21% of patients received treatment for their lipidic
disorder (statins or fibrates). (12)
As limitations to our work, we can mention that the
study period (2018-2021) was notably influenced by the COVID-19 pandemic, which reduced the number of
consultations and blood extractions. A second
limitation is that since the Argentine health
system is fragmented and segmented,
a tertiary public hospital dependent on the province of Buenos Aires does not cover the complete universe of
patients that are treated in this
system; there is also a public municipal health
system which is not interconnected with the former,
with the consequent lack of information flow
between one system and the other. The third limitation is linked to what
was stated above: being a third- level
hospital, outpatients are mostly referrals from primary care centers, or they are patients with multiple
comorbidities who require multidisciplinary care, which cannot be achieved at the first level. Moreover, in our universe of study there were hospitalized
patients, who per se presented
an intrinsic complexity.
The systematization and continuous process of detecting
patients with SHTG based on values obtained from
the laboratory, constitutes a simple and accessible strategy, which allows real-time
research of patients affected by this dyslipidemia.
In conclusion, a prevalence of 0.28% was found, which was within the upper range of what
was expected according to previous reports.
Our value at the higher
end of the range may probably be due to the
fact that our study included outpatients and inpatients at a tertiary hospital. On the other hand, the underuse of medication for the treatment of this severe dyslipidemia with a high risk of
pancreatitis stands out, despite the
fact that more than half of the patients had cardiovascular risk factors.
Conflicts of interest
None declared.
(See authors' conflict of interests forms on the web/Additional material.)
Ethical considerations
Not applicable.
©Revista Argentina de Cardiología
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