The Association of Statins on Cardiorespiratory Fitness and Exercise Adaptation

Retrospective Study of the Association of Statins on Cardiorespiratory Fitness and Exercise Adaptation: Database of the Cardiovascular Rehabilitation and Exercise Physiology Department of Heart Institute (InCor)

Statins are part of one of the largest groups of drugs prescribed worldwide used in the treatment of dyslipidemia. Despite the good therapeutic results of statins and their good tolerance on the part of patients, some adverse effects may occur during treatment. In skeletal muscle, statins can lead to mitochondrial dysfunction characterized by decreased adenosine triphosphate production, decreased oxidative phosphorylation capacity, increased concentration of reactive oxygen species, and decreased mitochondrial biogenesis.

Cardiorespiratory fitness is a physiological indicator that corresponds to the integration of the cardiovascular, pulmonary, muscular, and cellular (mitochondria) systems in capturing, transporting and using oxygen, commonly expressed as the maximum oxygen consumption. Several studies show a strong association of lower cardiorespiratory capacity with an increased risk of mortality from cardiovascular disease and mortality from all causes.

Combining the use of statins with lifestyle changes has been suggested in many medical guidelines. Physical exercise plays a fundamental role in improving cardiorespiratory fitness and controlling dyslipidemia. However, some studies suggest that the association of statin with physical training can negatively influence the adaptation and improvement of cardiorespiratory capacity. On the other hand, some studies show that the combination of statin and physical exercise does not negatively interfere with the maximum oxygen consumption.

To determine the impact of statins on cardiorespiratory fitness and adaptation to physical exercise, the investigators will use the database of the Cardiovascular Rehabilitation and Exercise Physiology Department at Heart Institute (Sao Paulo, Brazil), which currently has 33,804 maximal cardiopulmonary exercise tests. This large database, which is the gold standard of cardiorespiratory capacity (maximum oxygen consumption), will be used retrospectively with relevant information and a huge number of participants.

Therefore, the aim of this study will be to explore a large database to assess the effect of the use of statins and their relationship with cardiorespiratory capacity in physically active and sedentary individuals (with and without heart failure).

Study Overview

• Status: Completed
• Conditions: Statin Adverse Reaction
• Intervention / Treatment: Other: Sedentary; Drug: Statin; Other: Physical activity

Detailed Description

The investigators will use the database of the Cardiovascular Rehabilitation and Exercise Physiology Department at Heart Institute (Sao Paulo, Brazil) in an exploratory manner. The investigators will use filters to perform different analyzes and sub-analyses with different groups of patients. The investigators aimed to compare patients using statins and healthy controls (not using medications). The analysis strategy will be as following: 1) physically active and sedentary patients with normal cardiac function using statins and peak oxygen consumption (peak VO2); 2) physically active and sedentary patients with cardiac dysfunction (heart failure) using statins and peak VO2; 3) comparison between the hydrophilic and lipophilic classes of statins; 4) comparison between men and women; 5) retrospective information on clinical and laboratory variables and 6) test information on cardiorespiratory capacity and several variables associated with the mortality outcome.

The participants underwent cardiopulmonary exercise testing on a treadmill or bike (SensorMedics - Vmax Analyzer Assembly, Encore 29S) following a ramp protocol with constant load increase until exhaustion. Cardiorespiratory capacity will be determined by peak VO2, assessed at maximum exercise intensity, with a respiratory exchange ratio >1.10.

• Study Type: Observational
• Enrollment (Actual): 18557

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-900
      • Marcelo Rodrigues dos Santos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The population of the study are patients admitted in the Cardiovascular Rehabilitation and Exercise Physiology Department at Heart Institute Hospital (Sao Paulo, Brazil) for a cardiopulmonary exercise test.

Description

Inclusion Criteria:

• Maximal Cardiopulmonary Test on treadmill or bike.
• Test considered maximum from the metabolic point of view (Respiratory Quotient >1.10).

Exclusion Criteria:

• Incomplete patient data.
• Incomplete exam data.
• Chronic obstructive pulmonary disease
• Diagnosis of cancer

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sedentary Heart Failure with Reduced Ejection Fraction Without Statin; Sedentary Heart Failure with Reduced Ejection Fraction determined by echocardiogram; Without statin in the last 6 months.	Other: Sedentary; Physically inactive or sedentary participants.; Other Names: Physical inactivity
Sedentary Heart Failure with Reduced Ejection Fraction With Statin; Sedentary Heart Failure with Reduced Ejection Fraction determined by echocardiogram; With current use of statin.	Other: Sedentary; Physically inactive or sedentary participants.; Other Names: Physical inactivity; Drug: Statin; Chronic use of statin prescribed previously by the assistant physician.; Other Names: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor
Physically active Heart Failure with Reduced Ejection Fraction Without Statin; Physically active Heart Failure with Reduced Ejection Fraction determined by echocardiogram; Without statin in the last 6 months.	Other: Physical activity; Physically active participants; Other Names: Physical exercise
Physically active Heart Failure with Reduced Ejection Fraction With Statin; Physically active Heart Failure with Reduced Ejection Fraction determined by echocardiogram; With current use of statin.	Drug: Statin; Chronic use of statin prescribed previously by the assistant physician.; Other Names: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor; Other: Physical activity; Physically active participants; Other Names: Physical exercise
Healthy sedentary Without Statin; Sedentary and healthy participant without use of statin; Without statin in the last 6 months.	Other: Sedentary; Physically inactive or sedentary participants.; Other Names: Physical inactivity
Healthy sedentary With Statin; Participant with dyslipidemia and sedentary with current use of statin.	Other: Sedentary; Physically inactive or sedentary participants.; Other Names: Physical inactivity; Drug: Statin; Chronic use of statin prescribed previously by the assistant physician.; Other Names: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor
Healthy physically active Without Statin; Healthy, physically active participant without use of statin; Without statin in the last 6 months.	Other: Physical activity; Physically active participants; Other Names: Physical exercise
Healthy physically active With Statin; Participant with dyslipidemia and physically active with current use of statin.	Drug: Statin; Chronic use of statin prescribed previously by the assistant physician.; Other Names: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor; Other: Physical activity; Physically active participants; Other Names: Physical exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory Fitness	To determine whether the use of statins impairs the adaptation of the cardiorespiratory fitness in physically active individuals, with and without left ventricular dysfunction (heart failure), when compared with a matched sedentary control group.	From 1998 to 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Types of statins in Cardiorespiratory Fitness	To determine whether the type of statins (lipophilic or hydrophilic) has any adverse effect on the cardiorespiratory fitness in physically active individuals, with and without left ventricular dysfunction (heart failure), when compared with a matched sedentary control group.	From 1998 to 2017
Sex differences	To determine whether sex (men and women) is associated with statins and cardiorespiratory fitness impairment.	From 1998 to 2017
Cardiovascular mortality	To determine the association of functional capacity and cardiorespiratory fitness with cardiovascular mortality.	From 1998 to 2017
All-cause mortality	To determine the association of functional capacity and cardiorespiratory fitness with all-cause mortality.	From 1998 to 2017

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Marcelo R dos Santo, PhD, Instituto do Coração (INCOR)

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2019
• Primary Completion (Actual): June 20, 2023
• Study Completion (Actual): June 20, 2023

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: July 22, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CardioRehab Bank Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No