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Snapshot on Obesity and Cardiovascular Disease

  • Authors: George Boutsalis, PhD
  • CME / ABIM MOC / CE Released: 4/10/2023
  • Valid for credit through: 4/10/2024, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for cardiologists, primary care physicians, diabetologists and endocrinologists, nurses and nurse practitioners, and pharmacists.

The goal of this activity is for learners to be better able to understand the risk of cardiovascular disease (CVD) associated with obesity, and weight loss strategies to reduce the risk of CVD in obese patients.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Risk of CVD associated with obesity
    • Treatment strategies to manage obesity and reduce the risk of CVD


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  • George Boutsalis, PhD

    Senior Medical Education Director, Medscape, LLC 


    George Boutsalis, PhD, has no relevant financial relationships.

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    Associate Director, Accreditation and Compliance, Medscape, LLC


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  • Amy Bernard, MS, BSN, RN, NPD-BC, CHCP

    Senior Director, Accreditation and Compliance, Medscape, LLC


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Snapshot on Obesity and Cardiovascular Disease

Authors: George Boutsalis, PhDFaculty and Disclosures

CME / ABIM MOC / CE Released: 4/10/2023

Valid for credit through: 4/10/2024, 11:59 PM EST


The global incidence of obesity is on the rise. The "2013 AHA/TOS Guideline for the Management of Overweight and Obesity in Adults" uses the World Health Organization criteria to define overweight as a body mass index (BMI) ≥ 25 and < 30 kg/m[2] and obesity as a BMI ≥ 30 kg/m[2]. Furthermore, obesity is subdivided into further categories and classified as class 1, class 2, or class 3 (Table 1) Although BMI is strongly correlated with percent body fat across populations, there are limitations in its predictive ability to estimate body fat for any given individual, with considerable variation by sex, age, and race/ethnicity.

Table 1. Classification of Obesity by BMI in Adults[1]

BMI (kg/m2)


18.5 to 24.9

Normal weight

25 to 29.9


30 to 34.99

Class 1 obesity

35 to 39.99

Class 2 obesity

≥ 40

Class 3 obesity

Why does obesity matter in cardiology? The main reason it matters is because obesity is consistently associated with metabolic disorders and cardiovascular disease (CVD). States participating in the Behavioral Risk factor Surveillance System have reported a consistent rise in the number of adults with obesity (BMI > 30, or 30 lb overweight for a 5'4" person) -- in 1990, 10 states had a prevalence of obesity < 10% and no states had prevalence ≥ 15%. By 2000, no state had a prevalence of obesity < 10%, 23 states had a prevalence between 20% and 24%, and no state had prevalence ≥ 25%. By 2010, no state had a prevalence of obesity < 20%, but 36 states had a prevalence ≥ 25%; 12 of these states (Alabama, Arkansas, Kentucky, Louisiana, Michigan, Mississippi, Missouri, Oklahoma, South Carolina, Tennessee, Texas, and West Virginia) had a prevalence ≥ 30%.

Data from the AHA scientific statement on obesity and CVD reported that fat deposition in the myocardium results in insulin resistance, resulting in altered vascular resistance or altered autonomic function. One important association exists between obesity and heart failure -- a BMI > 25 is associated with a slight increase in the prevalence of heart failure with reduced ejection fraction (HFrEF); however, there is a direct linear relationship between obesity and heart failure with preserved ejection fraction (HFpEF) when the BMI is > 25. This does not mean that obesity is not important in HFrEF, it just means that the relationship is less strong.

There is also a significant disruption in the autonomic nervous system that is associated with obesity. There are multiple risk factors that cause obesity, such as physical inactivity, hypertension, dyslipidemia, poor diet, diabetes, smoking, and excess alcohol. These can result in cardiac QRS fragmentation and fibrosis, which can lead to ventricular arrhythmia and sudden cardiac death. Obesity can also result in atrial fibrosis and atrial myopathy, resulting in atrial fibrillation (AF). AF is no longer thought of as a purely electrical problem, but more as a myopathic problem. Although the abnormal impulses emanating from the pulmonary veins can elicit AF, the extra systoles in the context of a normal atrial structure will likely not result in fibrillation. However, the development of atrial myopathy leads to AF, and obesity is one of the strongest risk factors for that as evidenced in studies where weight loss was associated with a reduction in the prevalence and the burden of AF.

There are a number of ways to assess obesity: BMI, waist-to-height ratio, and waist-to-hip ratio. Which one is best? The ECHORN study assessing the relationship between these different measures of obesity and 10-year risk of CVD showed that the waist-to-hip ratio was a better indicator than BMI or waist-to-height ratio of obesity-related CVD.[2] Whole-body fat percentage and visceral adipose tissue mass, which are correlated with obesity-related complications, are not fully accounted for through BMI evaluation. However, the BMI remains useful since this measurement has been employed in numerous clinical studies to define "overweight," "obese," and "very obese" patients.

What about metabolically healthy obesity (MHO)? This refers to obese individuals without the metabolic abnormalities that commonly accompany excess adiposity, such as dyslipidemia, glucose dysregulation, and inflammation. The evidence has been inconsistent. Although some studies have shown that those with MHO have a similar risk of CVD as their nonobese metabolically active counterparts, other studies report that people with MHO have a significantly higher risk of CVD compared with metabolically normal weight patients.[3] The inconsistent results are related to how MHO is defined -- there is no standard for defining MHO, and the definition used to define this phenotype varies from study to study.

In overweight and obese patients with established CVDs and other chronic conditions, the "obesity paradox" refers to a protective effect of obesity, associated with decreased mortality. Multiple studies have demonstrated that overweight and obese patients may have a more favorable prognosis when compared to those with normal BMI after the onset of clinical CVD. However, there are many factors to consider when interpreting the obesity paradox, such as comorbidities, confounders, and selection bias. Notably, the paradox seems to keep defining obesity using BMI, which is not able to quantify body fat percentage and adiposity distribution, nor the degree of metabolic disturbances that it can underlie.[4]

Weight management and weight loss are fundamental goals in treating overweight and obesity, and should be part of a comprehensive multidisciplinary and interprofessional treatment plan to address both weight and any associated comorbidities, including behavioral interventions. The combination of medication and lifestyle modifications results in greater and sustained weight loss than either pharmacotherapy or lifestyle changes alone. Recently, novel medical pharmacotherapies that could impact obesity were approved by the FDA (Table 2), but for a long time, bariatric surgery was the best way to get a significant reduction in weight. The Swedish Obese Subjects study, a nonrandomized prospective study that looked at 2010 obese patients who had undergone bariatric surgery compared with 2037 contemporaneously matched controls, reported that patients who had undergone surgery had a 30% lower risk of total mortality and a 41% lower risk of coronary artery disease after a 15-year follow-up.[5] These procedures should be considered for patients with a BMI ≥ 40 kg/m[2] and for those with ≥ 1 severe weight-related condition and a BMI ≥ 35 kg/m[2] when therapeutic goals cannot be attained using structured lifestyle change and pharmacotherapy alone.[1]

Table 2. Prescription Medications Approved to Treat Overweight and Obesity (Adapted by NIH)[6]

Management Medication

Approved for

How It Works

Common Side Effects


Adults and children ≥ 12 years

  • Works in your gut to reduce the amount of fat your body absorbs from the food you eat
  • diarrhea
  • gas
  • leakage of oily stools
  • stomach pain



  • A mix of 2 medications: phentermine, which lessens your appetite, and topiramate, which is used to treat seizures or migraine headaches
  • May make you less hungry or feel full sooner
  • constipation
  • dizziness
  • dry mouth
  • taste changes, especially with carbonated beverages
  • tingling of your hands and feet
  • trouble sleeping



  • A mix of 2 medications: naltrexone, which is used to treat alcohol and drug dependence, and bupropion, which is used to treat depression or help people quit smoking
  • May make you feel less hungry or full sooner
  • constipation
  • diarrhea
  • dizziness
  • dry mouth
  • headache
  • increased blood pressure
  • increased heart rate
  • insomnia
  • liver damage
  • nausea
  • vomiting


Adults and children ≥ 12 years

  • Mimics a hormone called glucagon-like peptide-1 (GLP-1) that targets areas of the brain that regulate appetite and food intake
  • At a lower dose, this drug was FDA-approved to treat type 2 diabetes
  • nausea
  • diarrhea
  • constipation
  • abdominal pain
  • headache
  • increased heart rate



  • Mimics GLP-1, which targets areas of the brain that regulate appetite and food intake
  • Under different dosages, this drug was FDA-approved to treat type 2 diabetes as an injectable medication and as an oral pill
  • nausea
  • diarrhea
  • vomiting
  • constipation
  • abdominal (stomach) pain
  • headache
  • fatigue


People ≥ 6 years old with obesity due to specific genetic conditions only*

  • May reduce appetite and increase feeling of fullness
  • May increase resting metabolism (how the body burns calories)
  • Although it can help a person lose weight, it does not treat the genetic defects
  • injection site reaction
  • skin darkening
  • nausea
  • disturbance in sexual arousal
  • depression and suicidal ideation
  • risk of serious adverse reactions in neonates and infants with low birthweight

(Other medications that curb your desire to eat include)

  • Phentermine
  • Benzphetamine
  • Diethylpropion
  • Phendimetrazine


  • Increases chemicals in your brain to make you feel you are not hungry or that you are full
  • Note: FDA-approved only for short-term use -- up to 12 weeks
  • dry mouth
  • constipation
  • difficulty sleeping
  • dizziness
  • feeling nervous
  • feeling restless
  • headache
  • raised blood pressure
  • increased heart rate
FDA, US Food and Drug Administration; NIH, National Institutes of Health.
*Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency/Bardet-Biedl syndrome.
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