Revista Methodo: Investigación Aplicada a las Ciencias Biológicas. Universidad Católica de Córdoba.
Jacinto Ríos 571 Gral. Paz. X5004FXS. Córdoba. Argentina. Tel.: (54) 351 4517299 / Correo:
methodo@ucc.edu.ar / Web: methodo.ucc.edu.ar |ARTICULO ORIGINAL Rev. Methodo 2024;9(2):08-14.
ARTICULO ORIGINAL Rev. Methodo 2024;9(2):08-14
https://doi.org/10.22529/me.2024.9(2)03
Recibido 27 Dic. 2023 | Aceptado 24 Nov. 2023 |Publicado 05 Abr 2024
Achieving target blood pressure and LDL Cholesterol does not
prevent the progression of atherosclerotic plaque burden in a
high-risk population
Alcanzar la presión arterial y el colesterol LDL objetivo no
previene la progresión de la carga de placa aterosclerótica en
una población de alto riesgo
Hernán Alejandro Pérez
1
, Enrique A. Majul
2
, Ana Laura Oliszynski
3
, Delia Agustin
3
, Delfina
Bocchetto
3
, Candela Albrecht
3
, Iara Milena Báez
3
, Ignacio Foa Torres
3
, Luz María González Rinaldi
3
,
Sofía Lambrechts
3
, Sonia Muñoz
4
, Mariana Carrillo
4
, J. David Spence
5
, Néstor H. García
4
1. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud. Catedra Fisiología Medica
2.
Universidad Católica de Córdoba. Facultad de Ciencias de la Salud. Maestría Nutrición Médica y Diabetología. Clínica Universitaria Reina Fabiola.
3. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud
4. Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET)
5.Robarts Research Institute, Western Ontario University
Correspondencia: Hernán Alejandro Pérez E-mail: hernan.perez@ucc.edu.ar
Abstract
BACKGROUND AND AIMS: Atherosclerotic disease is a huge health burden worldwide, and its
prevention is largely focused on controlling traditional risk factors, despite limited effectiveness in
preventing cardiovascular disease (CVD) events. Improved risk stratification can be achieved by
identifying the progression of total plaque area (TPA) using carotid ultrasound, with the risk of CVD events
doubling when progression is detected over a 1-year interval. We hypothesize that blood pressure and serum
LDL cholesterol control at target values (current clinical guidelines) are insufficient to reduce the
progression of atherosclerosis in persons with high CVD risk
METHODS AND RESULTS: Prospective, observational study of 742 participants with high
cardiovascular risk in a cardiovascular primary prevention program. Two ultrasound measurements of TPA
were acquired for each participant for at least one year. We studied only those who maintained a blood
pressure below 130/80 mmHg and serum Low-Density Lipoprotein Cholesterol (LDL-C) below 100 mg/dl
throughout the study interval (57 participants). Participants with plaque progression of TPA > 5 mm2, were
compared to those with TPA changes of 5 mm2 or less (non-progression group) using a multivariable
logistic regression controlling for cardiovascular risk factors.
We identified TPA progression in 22 of 57 (38.6%) participants. No differences were detected for any
covariate when comparing progression versus non-progression.
CONCLUSION: Progression of TPA occurs in as many as 38.6% of individuals despite maintaining BP
below 130/80 and serum LDL-C below 100 mg/dl. TPA evaluation may help address the limitations of
established guidelines for the prevention of CVD events in high-risk individuals.
Keywords: Subclinical Atherosclerosis, Cardiovascular Risk factors, Arterial Hypertension, Lipids
08
Pérez H, Majul E, Oliszynski A L, Delia A, Bocchetto D, Albrecht C, Baez I M, Foa Torres I, González Rinaldi L M,
Lambrechts S, Muñoz S, Carrillo M, Spence J D, García N. Achieving target blood pressure and LDL Cholesterol does
not prevent the progression of atherosclerotic plaque burden in a high-risk population
Revista Methodo: Investigación Aplicada a las Ciencias Biológicas. Universidad Católica de Córdoba.
Jacinto Ríos 571 Gral. Paz. X5004FXS. Córdoba. Argentina. Tel.: (54) 351 4517299 / Correo:
methodo@ucc.edu.ar / Web: methodo.ucc.edu.ar| ARTICULO ORIGINAL Rev. Methodo 2024;9(2):08-14.
Resumen
INTRODUCION: La enfermedad aterosclerótica es una enorme carga para la salud en todo el mundo, y su
prevención está basada en gran medida en el control de los factores de riesgo tradicionales, a pesar de la
eficacia limitada en la prevención de eventos cardiovascular (ECV). La mejoría en la estratificación del
riesgo se puede lograr a través de la detección de progresión del área total de la placa (TPA) medida por
ecografía carotidea, la cual ha demostrado duplicación del riesgo basal en estos pacientes en un intervalo
de 1 año. Nuestra hipótesis es que el control de la presión arterial y el colesterol LDL sérico en valores
objetivo (según guías clínicas actuales) son insuficientes para reducir la progresión de la aterosclerosis
en personas sin eventos previos, con alto riesgo cardiovascular.
METODOS Y RESULTADOS: Estudio observacional prospectivo de 742 participantes con alto riesgo
cardiovascular en un programa de prevención primaria cardiovascular. Se determinaron dos mediciones de
ultrasonido de TPA para cada participante durante al menos un año. Incluimos en el análisis 57 participantes
que mantuvieron una presión arterial por debajo de 130/80 mmHg y un colesterol sérico de lipoproteínas
de baja densidad (LDL-C) por debajo de 100 mg/dl durante todo un año. Los participantes con progresión
de la placa de TPA definida como aumento sobre el basal mayor de 5 mm2 se compararon con aquellos
con cambios de TPA de 5 mm2 o menos (grupo sin progresión) mediante análisis de regresión
logística multivariable.
Después de una media de estadía en programa de casi 8 años, con Presión Arterial de 120.4 + 9/68.6 + 8
mmHg y LDL colesterol de 81 + 25 mg/dl, identificamos progresión de TPA en 22 de 57 (39%)
participantes. No detectándose diferencias para ninguna covariable al comparar progresión versus no
progresión.
CONCLUSIÓN: La progresión de TPA ocurre hasta en el 39% de los individuos a pesar de mantener la
presión arterial por debajo de 130/80 y el LDL-C sérico por debajo de 100 mg/dl. La evaluación de TPA
puede ayudar a resolver las limitaciones de las pautas establecidas para la prevención de eventos de ECV
en personas de alto riesgo.
Palabras clave: Ateroesclerosis Subclínica, Factores de Riesgo Cardiovasculares, Hipertensión
Arterial, Lípidos.
Introduction
Deaths from cardiovascular disease (CVD)
events are a major health problem in the world
and currently account for about 30% of overall
mortality. Every year, more people die from
CVD than from any other cause
1,2
. More
importantly, a substantial proportion of deaths
(about 50%), occur in people under 70 years of
age, the population's most productive years of
life
3
. It has been estimated that nearly half of men
and one-third of women will suffer from some
manifestation of ischemic heart disease during
their lifetimes
4
. Atherosclerosis is the leading
cause of these events, but because it is
asymptomatic for a long period
5
, early diagnosis
is very difficult. Current guidelines recommend
diagnosing and treating patients according to the
risk presented by clinical scores (Framingham
Risk Score
6
(FRS), SCORE
7
, and others, which
are derived from classic cardiovascular risk
factors). Assman et al. reported that among
patients suffering an acute myocardial infarction,
45% had a low Prospective Cardiovascular
Munster Study (PROCAM) risk score
8
. In a
prospective study in Germany, among patients
who had a myocardial infarction, only 21.2%
were classified as high-risk by a PROCAM
score, whereas 84.9% were classified as high-
risk by measurement of carotid total plaque area
(TPA)
9
. The traditional approach to assessing
risk has two problems: a low sensitivity to
identify patients at high cardiovascular risk
10
,
and in clinical studies, no more than 50%
effectiveness in reducing cardiovascular events,
as seen in the biggest multifactorial intervention
in diabetic patients
11
.
A significant proportion of this morbidity and
mortality could be prevented by targeting
interventions for people at high risk of CVD,
both for those with established disease and for
those at high risk of developing the disease
12,13,14
.
One strategy to classify and treat patients at risk
is to use carotid TPA measured by ultrasound,
which reclassifies more patients as high-risk and
is very effective in decreasing cardiovascular
events in a high-risk cohort through prevention
15
.
TPA is much more predictive of risk than carotid
intima-media thickness (CIMT) and as predictive
as the Coronary Calcium Score
16
. Furthermore,
TPA may progress or regress within 3 months,
providing the possibility to assess and adjust
preventive therapy in clinically meaningful time
frames
17
. In 2002, Spence et al. found that
09
Pérez H, Majul E, Oliszynski A L, Delia A, Bocchetto D, Albrecht C, Baez I M, Foa Torres I, González Rinaldi L M,
Lambrechts S, Muñoz S, Carrillo M, Spence J D, García N. Achieving target blood pressure and LDL Cholesterol does
not prevent the progression of atherosclerotic plaque burden in a high-risk population
Revista Methodo: Investigación Aplicada a las Ciencias Biológicas. Universidad Católica de Córdoba.
Jacinto Ríos 571 Gral. Paz. X5004FXS. Córdoba. Argentina. Tel.: (54) 351 4517299 / Correo:
methodo@ucc.edu.ar / Web: methodo.ucc.edu.ar| ARTICULO ORIGINAL Rev. Methodo 2024;9(2):08-14.
patients whose TPA progressed by 0.05 cm2 in
the first year of follow-up were 2.1 times (95%
CI, 1.2 to 3.6; p=0.005) more likely to have had
a stroke, myocardial infarction, or vascular death
over 5 years, than patients who had regression or
no change in plaque area
18
. In high-risk patients
with asymptomatic carotid stenosis in Canada,
“treating arteries” as opposed to treating
cardiovascular risk factors was associated with a
> 80% reduction in the two-year risk of stroke
and myocardial infarction15. Among moderate-
risk patients aged> 65 years attending prevention
clinics in Argentina between 2011 and 2015,
“treating arteries” was associated with a decline
in the annual risk of CVD events from 5.8% to
2.35%
19
. We hypothesized that blood pressure
and serum LDL cholesterol control at target
values (recommended in current clinical
guidelines) is not sufficient to reduce the
progression of atherosclerosis in patients with
high cardiovascular (CV) risk.
Objectives
1. Evaluate the progression of TPA in high-risk
patients whose blood pressure and serum LDL
cholesterol are controlled.
2. Determine if classical cardiovascular risk
factors and time between TPA studies are
associated with the progression of TPA.
Methods
Study design and population: The study
population was composed of patients referred by
physicians to a Light and Force and Railroad
Unions Health Maintenance Organizations (Luz
y Fuerza and Obra Social Ferroviaria),
participating in an atherosclerosis prevention
program (LifeQualityA) conducted by Blossom
DMO Argentina. The program was initiated in
2008 and continues at present, with a total of
4531 participants, white Latin men represent
41.3%, mean+SD age (58+14 years), and is
based in Buenos Aires and Cordoba, Argentina.
The inclusion of a volunteer in the program
started with the stratification of cardiometabolic
risk by using t