Revista Methodo: Investigación Aplicada a las Ciencias Biológicas. Universidad Católica de Córdoba.

Jacinto Ríos 571 Bº 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

, Enrique A. Majul

, Ana Laura Oliszynski

, Delia Agustin

, Delfina

Bocchetto

, Candela Albrecht

, Iara Milena Báez

, Ignacio Foa Torres

, Luz María González Rinaldi

Sofía Lambrechts

, Sonia Muñoz

, Mariana Carrillo

, J. David Spence

, Néstor H. García

1. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud. Catedra Fisiología Medica

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

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 Bº 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

. 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

. Atherosclerosis is the leading

cause of these events, but because it is

asymptomatic for a long period

, early diagnosis

is very difficult. Current guidelines recommend

diagnosing and treating patients according to the

risk presented by clinical scores (Framingham

Risk Score

(FRS), SCORE

, 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

. 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)

. The traditional approach to assessing

risk has two problems: a low sensitivity to

identify patients at high cardiovascular risk

and in clinical studies, no more than 50%

effectiveness in reducing cardiovascular events,

as seen in the biggest multifactorial intervention

in diabetic patients

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

TPA is much more predictive of risk than carotid

intima-media thickness (CIMT) and as predictive

as the Coronary Calcium Score

. Furthermore,

TPA may progress or regress within 3 months,

providing the possibility to assess and adjust

preventive therapy in clinically meaningful time

frames

. In 2002, Spence et al. found that

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 Bº 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

. 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%

. 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 the FRS based on body mass index

(BMI). Those subjects with a 10-year risk score

≤ 6% were assigned to management by a General

Practitioner (GP), while those with scores> 6%

were re-tested using the Framingham Post-test

algorithm. After this stratification with the

Framingham Post-test algorithm, subjects with

scores <20% were assigned to follow-up by GP

while those with scores ≥ 20% were assigned to

the cardiometabolic high-risk group as the High-

Risk Control Service thereafter. This service

consists of a multidisciplinary team of

physicians, nutritionists, educators, gym trainers,

psychologists, and health workers.

Also, the follow-up subjects meeting the criteria

of controlled risk factors were awarded free-of-

charge medication. These criteria were: HbA1c

<7%, Total Cholesterol <200 mg/dl, and BP <

130/80 mmHg, among others19. The present

study was carried out in participants enrolled

between November 2017 and May 2021. In total

there were 742 participants, of these 184

participants had more than one study and no

cardiovascular events. After excluding Diabetic

participants, current smokers, and participants

with out-of-range blood pressure and cholesterol

values for the analysis, we analyzed 57

participants with the inclusion criteria (Blood

Pressure less than 130/80, Serum LDL

Cholesterol less 100 mg/dl and Framingham

score at 10 years more than 20%) (Figure 1).

Figure 1. Block Diagram of the research.

The protocol was approved by the Committee on

Independent Institutional Ethics of the National

University of Córdoba and the Rusculleda

Foundation. Reader reliability was estimated by

randomly assigning scans of 22 patients to

interpretation by 2 different readers.

Inclusion and Exclusion criteria: For this

analysis, we include participants over 40 years of

age, with a risk of acute myocardial infarction

greater than 20% at ten years based on TPA,

participants (with or without antihypertensive

medication or Hypertension) with blood pressure

< 130 mmHg systolic and < 80 mmHg diastolic

based on blood pressure determination in clinical

follow-up, ambulatory blood pressure

monitoring or home blood pressure monitoring,

LDL-C <100 mg/dl in at least two separate

measurements >3 months apart, and written

informed consent given. Excluded were current

smokers, participants who had Type I or type II

diabetes, a history of previous cardiovascular

events, a history of neoplasm, kidney disease

(eGFR less than 60 ml/min), endocrinological

disease, rheumatological disease, immunological

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 Bº 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.

disease, those medicated with

immunosuppressants, and those with a history of

drug and/or alcohol abuse.

TPA determination: Measurement of TPA was

performed with a high-resolution ultrasound

machine (Ultrasound system Mindray M5,

Shenzhen, P. R. China) and a linear probe

between 5 to 10 MHz. It was performed by a

single operator, informed of the participant’s sex,

but blind to the participant’s history of vascular

disease and risk factors (blood pressure, serum

lipid levels, glycemia, and HbA1c). TPA was

measured as previously described

. “Plaque was

defined as a local thickening of the intima >1 mm

in thickness. Measurements were made in

magnified longitudinal views of each plaque seen

in the right and left common, internal, and

external carotid arteries. The plane in which the

measurement of each plaque was made was

chosen by panning around the artery until the

view showing the largest extent of that plaque

was obtained. The image was then frozen and

magnified, and the plaque was measured by

tracing around the perimeter with a cursor on the

screen. The microprocessor in the scanner then

displayed the cross-sectional area of the plaque.

The operator then moved on to the next plaque

and repeated the process until all visible plaques

were measured. The sum of the cross-sectional

areas of all plaques seen between the clavicle and

the angle of the jaw was taken as total plaque

area

Hypertensive patients: Patients with a previous

diagnosis of hypertension and/or taking

antihypertensive medication.

Hypercholesterolemic patients: Patients with a

previous diagnosis of hypercholesterolemia

and/or medication to treat dyslipidemia.

Blood pressure determination: Blood pressure

was taken as the mean of three measurements

performed on the left arm in the sitting position

after five minutes of rest (OMRON Hem 705

sphygmomanometer, Vermont Hills, IL, USA).

Serum cholesterol and triglycerides

determination: Blood lipids were measured

from whole blood samples using routine methods

in a central laboratory after a 12-hour fast (LACE

Laboratory, Córdoba, ARG).

Follow-up: Carotid TPA determinations were

made at baseline and at least one year later, with

three additional visits made during this interval

for measuring vital signs and laboratory results.

All patients were treated according to established

clinical guidelines

21,22,23,24,25

, but focusing on

TPA evolution criteria. Plaque area regression

was defined as a decrease of ≥5 mm

from

baseline; progression was defined as an increase

of ≥5 mm2 from baseline; and stability was

defined as either an increase or decrease of < 5

mm2, based on a previous study

. We divided

the patients into two groups: progression vs.

non-progression if the plaque regressed or was

stable.

Statistical Analysis

Descriptive analyses include absolute

frequencies, percentages, the mean and standard

deviation for quantitative variables that follow a

normal distribution, and median and interquartile

range for variables with a non-normal

distribution. Paired or unpaired t-tests were used,

as required by the type of analysis appropriate to

the hypothesis to be analyzed. Multiple

regression analysis was used to determine the

factors associated with progression status.

Reliability was estimated for the entire sample.

The accepted level of statistical significance for

rejecting null hypotheses was p<0.05.

Results

In total 742 participants were followed in this

period, of which 57 people met the criteria for

this study (mean age 71 + 8 years, 70% female,

all white Latin). The average Risk post-TPA at

10 years for Acute Myocardial Infarction was

very high (39.3 +18 %), the blood pressure

(120.4/68.6 mmHg) and LDL-C (81 mg/dL)

were at target levels during the year of study

(Table 1 and 2).

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 Bº 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.

We found that 22 of 57 participants (38.6%) had

plaque progression (Table 3).

A Multiple regression analysis was performed

with the evolution of TPA as the response

variable and age, sex, systolic blood pressure,

LDL-C, total cholesterol,Triglyceride/HDL-C

ratio, creatinine, and time between studies as

dependent variables, and we did not find any

significant difference in variables, comparing

progression vs. non-progression (Table 4). To

determine if the status of Hypertension or

Hypercholesteremia were relevant to these

findings, a logistic regression model was carried

out, using the evolution (progression/non-

progression) at the study as the dependent

variable, and age, sex, systolic blood pressure,

serum LDLc, triglycerides-HDL ratio,

creatinine, time between studies, presence of

hypertension, presence of hypercholesterolemia

of the second study as independent variable and

did not find an association with the occurrence of

progression (Table 4).

Discussion

Current treatment of patients at high CV risk

continues to be based on control of risk factors,

even though there are known limitations to that

approach. Current diagnostic techniques, such as

the measurement of TPA, improves risk

stratification, as demonstrated by our working

group in Argentina

, Fuster et al. in the United

States

, and Romanens in Switzerland.

Regardless of the initial risk level (low,

intermediate, high, very high), the suggested

therapeutic goals in the management of these

patients remain static, irrespective of the effect of

the treatment on the progression of

atherosclerosis. A meta-analysis reported a

reduction in CV events with LDL cholesterol

values much lower than the 70 mg/dl suggested

presently

. A study in > 4,000 patients reported

that renal failure and advanced age were related

to “resistant atherosclerosis,” a situation

identified in patients who, despite having very

low levels of LDL-C, continue to have

progression in their load of atherosclerosis

burden

. Plasma levels of toxic metabolites

produced by the intestinal microbiome were

associated with increased TPA not explained by

traditional risk factors (“unexplained

atherosclerosis”)

. In our study, an association

of age or creatinine level with progression as

independent factors was not reproduced,

probably because of the small number of

patients, and the restricted range of these

variables

. The ratio of Tg/HDL-C, recently

shown to identify metabolic syndrome and

insulin resistance, and an association with high

TPA

, was not predictive of progression in our

population, perhaps for the same reasons.

Because factors other than traditional risk factors

account for approximately half of plaque burden

in linear regression modeling, treating only

traditional risk factors to consensus target levels

fails approximately half of patients: they have

plaque progression, with twice the risk of those

with non-progression. Measuring the burden of

atherosclerosis not only permits more precise

risk stratification, but also determines the

effectiveness of treatment, and identifies patients

at higher risk who need more intensive therapy

based on “treating arteries” to be sure that the

treatment instituted is effective.

Limitations

The selection of our subjects was not based on a

random population sample. Our population was

derived from a follow-up cohort previously

described, and the great majority was older than

60 years old, which limits the extrapolation of

results to the general population. Even when our

study has few participants, all these had blood

pressure and serum LDL Cholesterol at target

levels, which in real life follow up is very

difficult.

Conclusions

Our data evaluating a population with high CVD

risk, which is representative of patients in real-

life medical practice, show that controlling blood

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 Bº 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.

pressure and LDL-C target levels does not

prevent the progression of atherosclerotic plaque

in a substantial proportion of patients. Therapy

based on measurement of plaque burden may be

more effective than simply treating risk factors to

target levels.

Bibliografía

1. WHO. Global atlas on cardiovascular

disease prevention and control. Geneva,

2011.

2. WHO. Global status report on non-

communicable diseases 2014. Geneva,

2014.

3. WHO. The World Health Report 2002:

reducing risks, promoting healthy life.

Geneva, 2002.

4. Nichols M, Townsend N, Luengo-

Fernandez R, et al. European

Cardiovascular Disease Statistics 2012.

European Heart Network, Brussels and

European Society of Cardiology.

Sophia Antipolis. 162.

5. Pattersson PP, Yang Cao, Torbjorn B,

et al. Body fat percentage and CRP

correlates with a composite score of

vascular risk markers in healthy, young

adults - The Lifestyle, Biomarkers, and

Atherosclerosis (LBA) study. BMC

Cardiovasc Disord. 2020; 20(1): 77.

6. d'Agostino RB Sr, Grundy S, Sullivan

LM, Wilson P; CHD Risk Prediction

Group. Validation of the Framingham

coronary heart disease prediction

scores: results of a multiple ethnic

groups investigation. JAMA. 2001;

286: 180-187.

7. European Guidelines on CVD

Prevention in Clinical Practice 2016.

Eur J Prev Cardiol. 2016; 23(11): NP1-

NP96.

8. Assmann G, Schulte H, Cullen P,

Seedorf U. Assessing risk of myocardial

infarction and stroke: new data from the

Prospective Cardiovascular Munster

(PROCAM) study. Eur J Clin Invest.

2007;37(12):925-32.

9. Adams A, Bojara W, Romanens M.

The Determination of the Plaque

Burden on the Carotid Artery with

Ultrasound Significantly Improves the

Risk Prediction in Middle-Aged

Subjects Compared to PROCAM: An

Outcome Study. Cardiol Res.

2020;11(4):233-8.

10. Cooney MT, Dudina AL and Graham

IM. Value and Limitations of Existing

Scores for the Assessment of

Cardiovascular Risk. A Review for

Clinicians. J Am Coll Cardiol. 2009;

54: 1209-1227.

11. Gaede P, Lund-Andersen H, Parving

H-H, et al. Effects on multifactorial

intervention on mortality in Type 2

Diabetes. N Engl J Med. 2008; 358:580-

591.

12. Lopez AD et al. Global and regional

burden of disease and risk factors, 2001:

systematic analysis of population health

data. Lancet. 2006; 367(9524): 1747–

57.

13. Manuel DG et al. Revisiting Rose:

strategies for reducing coronary heart

disease. BMJ. 2006; 332: 659–662.

14. WHO. Prevention of recurrent heart

attacks and strokes in low- and middle-

income populations.Evidence-based

recommendations for policy makers

and health professionals. Geneva, 2003.

15. Spence JD, Hackam DG. Treating

Arteries Instead of Risk Factors A

Paradigm Change in Management of

Atherosclerosis. Stroke. 2010; 41:

1193-1199.

16. Baber U, Mehran R, Sartori S, Schoos

MM, Sillesen H, Muntendam P et al.

Prevalence, impact, and predictive

value of detecting subclinical coronary

and carotid atherosclerosis in

asymptomatic adults: the BioImage

study. J Am Coll Cardiol.

2015;65(11):1065-74.

17. Spence JD. Time course of

atherosclerosis regression.

Atherosclerosis. 2014;235(2):347-8.

18. Spence JD, Eliasziw M, DiCicco M,

Hackam DG, Galil R and Lohmann T.

Carotid plaque area: a tool for targeting

and evaluating vascular preventive

therapy. Stroke. 2002; 33:2916-22.

19. Perez HA, Adeoye AO, Aballay L et

al. An Intensive follow up in subject

with cardiometabolic high risk. Nutr

Metab Cardiovas. 2021; 31: 2860-2869.

20. D’Agostino RB, Vasan RS, Pencina

MJ et al. General Cardiovascular risk

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 Bº 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.

profile for use in primary care. The

Framingham Heart Study. Circulation.

2008; 117: 743-753.

21. Arterial Hypertension Guide. SAHA.

[WEB]

http://www.saha.org.ar/pdf/GUIA_SA

HA_VERSION_COMPLETA.pdf

22. Diabetes Guide. Argentine Diabetes

Society.

[WEB]http://www.diabetes.org.ar/docs

/2010_10_SAD_Guia_del_Tratamiento

_de_la_D M2.pdf

23. NCEP III: Executive summary of the

third report of the National Cholesterol

Education Program Expert Panel on

Detection, Evaluation, and Treatment of

High Blood Cholesterol in Adults

(Adult Treatment Pane III). JAMA.

2001; 285: 2486-2497.

24. National Guide to the Treatment of

Tobacco Addiction.

[WEB]http://www.femeba.org.ar/docu

mentos/download/436-

tratamiento_adiccion_tabaco.pdf

25. WHO Guides 2010 for Physical

Activity.

[WEB]http://whqlibdoc.who.int/public

ations/2010/9789243599977 spa.pdf.

26. Perez HA, Garcia NH, Spence JD, et

al. Adding carotid total plaque area to

the Framingham risk score improves

cardiovascular risk classification.

Archiv of Med Sci.2016; 12(3): 512-

520.

27. Usman B, Mehran S, Sartori M, et al.

Detection and impact of subclinical

coronary and carotid atherosclerosis on

cardiovascular risk prediction and

reclassification in asyntomatic us

adults: insights from the high-risk

plaque bioimage study. J Am Coll

Cardiol. 2014; 63: A998.

28. Romanens M, Sudano I, Adams A, et

al. Advanced carotid atherosclerosis in

middle-aged subjects: comparison with

PROCAM and SCORE risk categories,

the potential for reclassification and

costefficiency of carotid ultrasound in

the setting of primary care. Swiss Med

Wkly. 2019; 149: w20006.

29. Sabatine MS, Wivviott SD, KyungAh

Im, et al. Efficacy and Safety of Further

Lowering of Low-Density Lipoprotein

Cholesterol in Patients Starting with

Very Low Levels A Meta-analysis.

JAMA Cardiology. 2018; 3(9): 823-

828.

30. Spence DJ and Solo K. Resistant

Atherosclerosis. The need to monitor of

plaque burden. Stroke. 2017; 48(6):

1624-1629.

31. Bogiatzi C, Gloor G, Allen-Vercoe E

et al. Metabolic products of the

intestinal microbiome and extremes of

atherosclerosis. Atherosclerosis. 2018,

273: 91-97.

32. Bland JM, Altman DG. Correlation in

restricted ranges of data. BMJ. 2011;

342: 577.

33. Azarpazhooh MR, Najafi F, Darbandi,

et al. Triglyceride/High-Density

Lipoprotein Cholesterol Ratio: A Clue

to Metabolic Syndrome, Insulin

Resistance, and Severe Atherosclerosis.

Lipids. 2021; 56: 405-412.