Challenges in Cardiovascular Evaluation and Management of Obese Patients

JACC State-of-the-Art Review

Rosana G. Bianchettin, MD; Carl J. Lavie, MD; Francisco Lopez-Jimenez, MD

J Am Coll Cardiol. 2023;81(5):490-504.

Abstract and Introduction

Abstract

Many unique clinical challenges accompany the diagnosis and treatment of cardiovascular disease (CVD) in people living with overweight/obesity. Similarly, physicians encounter numerous complicating factors when managing obesity among people with CVD. Diagnostic accuracy in CVD medicine can be hampered by the presence of obesity, and pharmacological treatments or cardiac procedures require careful adjustment to optimize efficacy. The obesity paradox concept remains a source of confusion within the clinical community that may cause important risk factors to go unaddressed, and body mass index is a misleading measure that cannot account for body composition (eg, lean mass). Lifestyle modifications that support weight loss require long-term commitment, but cardiac rehabilitation programs represent a potential opportunity for structured interventions, and bariatric surgery may reduce CVD risk factors in obesity and CVD. This review examines the key issues and considerations for physicians involved in the management of concurrent obesity and CVD.

Introduction

Physicians face a multitude of clinical challenges when managing cardiovascular disease (CVD) in people with overweight/obesity, from diagnosis through to long-term treatment, because of the complex, multifaceted, and progressive nature of obesity and its impact on CVD outcomes (Figure 1).^[1,2] Obesity is a heterogenous chronic condition affecting many people seen in the cardiology department, and although the World Health Organization defines the severity of obesity according to body mass index (BMI), a range of anthropometric measures that more accurately capture central adiposity (eg, waist-hip ratio, waist circumference) may provide better means of assessing the associated CVD risk.^[3–13] Overweight, obesity, and severe class III or (previously called) morbid obesity are typically described as having a BMI of 25–29.9, ≥30, and ≥40 kg/m², respectively, for Caucasian individuals, whereas lower thresholds exist for Asian populations.^[8,14] Direct and indirect obesity-related mechanisms raise CVD risk via multiple pathways involving structural, functional, humoral, and hemodynamic alterations associated with the onset of cardiometabolic disease and complications associated with fat mass.^[1,13]

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Figure 1.

Obesity and Cardiovascular Disease: Proposed Pathophysiology of Obesity Cardiomyopathy
This diagram shows the central hemodynamic alterations that result from excessive adipose accumulation in severely obese patients and their subsequent effects on cardiac morphology and ventricular function. Left ventricular (LV) hypertrophy in severe obesity may be eccentric or concentric. Factors influencing LV remodeling and geometry include severity and duration of obesity; duration and severity of adverse LV loading conditions (particularly hypertension); and, possibly, neurohormonal and metabolic abnormalities such as increased sympathetic nervous system tone, activation of the renin-angiotensin-aldosterone system, insulin resistance with hyperinsulinemia, leptin resistance with hyperleptinemia, adiponectin deficiency, lipotoxicity, and lipoapoptosis. These alterations may contribute to the development of LV failure. LV failure, facilitated by pulmonary arterial hypertension from sleep apnea/obesity hypoventilation, may subsequently lead to right ventricular (RV) failure. Figure provided with kind permission from Lavie et al.² LA = left atrial.

People with CVD and overweight/obesity often need support to understand and address their level of CVD risk, and a long-term multidisciplinary approach may be required to achieve and maintain a healthier body weight. This narrative review explores the unique clinical challenges relating to the management of CVD in the setting of obesity as well as the key issues to consider when addressing obesity among people living with CVD. The Central Illustration presents an overview of the reciprocal clinical issues associated with the concurrent management of CVD and obesity, and this review focuses on patient-centric and evidence-based approaches to care for the improvement of treatment outcomes and quality of life.

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Central Illustration.

Clinical Challenges in People With Obesity and CVD
The direction of the arrows represents the causal relationship. CVD = cardiovascular disease; DOAC = direct oral anticoagulants; HTN = hypertension; LMWH = low molecular weight heparin; MACE = major adverse cardiovascular events; PCI = percutaneous intervention; UFH = unfractionated heparin.

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Table 1. A Summary of Key Obesity-Related Challenges That May Affect the Diagnostic Performance of Cardiovascular Modalities
Cardiovascular Modality	Obesity-Related Challenges Affecting Diagnostics
Electrocardiogram	Displacement of the heart (because of elevation of the diaphragm in the supine position) Increased cardiac workload and associated cardiac hypertrophy Widening of distance between the heart and the recording electrodes Chronic lung disease Low QRS voltage + leftward trend in the axis Nonspecific T-wave flattening Increased incidence of inferior MI false-positive criteria Increased heart rate
Transthoracic echocardiography	Poor acoustic window (caused by pulmonary disease, body habitus and respiratory motion) Differentiation between subepicardial adipose tissue and pericardial effusion Epicardial adipose tissue (pseudo pericardial effusion) and pericardial fluid underestimation Adipose depots within the heart tissue
Stress testing
Exercise echocardiography	Low sensitivity Difficulty exercising
SPECT	Table weight limits Radioisotope dosing limits Reduced signal-to-noise ratio
Thalium-201 myocardial perfusion imaging	Reduced accuracy
CTCA	Precluded in people with BMI >40 kg/m²
CMR	Restrictive bore size Claustrophobia Reduced quality of image Extended distance between heart and chest coils
Interventional radiology	Poor visualization of target areas Restricted length of equipment Accommodation of larger individuals within CT or CMR scanners Radioisotope dosing limits Safety concerns regarding dosing where multiple procedures are required

CMR = cardiac magnetic resonance; CT = computerized tomography; CTCA = computerized tomography coronary angiography; MI = myocardial infarction; SPECT = single photon emission computed tomography.

Table 2. Therapeutic Challenges in People With CVD and Obesity
Therapeutic Factors	Challenges in People With CVD and Obesity
Lifestyle modifications
Diets	Multiple and conflicting dietary recommendations: low calorie, high/low protein, low fat, low sodium, low fluids, high/low green vegetables.
Physical activity	Obstacles to regular exercise participation with obesity: • Lower back pain, knee or hip osteoarthritis; • Sever deconditioning, leading to significant dyspnea; • OSA: increases feelings of tiredness; • Asthma.
Smoking cessation	Induces weight gain and increases risk of T2DM because of increased food intake and decreased suppressant effects of nicotine from the central nervous system.
Pharmacology	Tailoring pharmacotherapy is difficult because of unique pharmacokinetics and pharmacodynamics factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated.
Pharmacokinetics	Increase volume of distribution: increase in fat mass generates higher volume of distribution of lipophilic drugs. The loading dose of drugs with distribution restricted to lean tissues should be based on the ideal body weight of patients with obesity. Increase/decrease hepatic metabolism: increase hepatic blood flow. In the presence of nonalcoholic fatty liver disease, blood flow decrease. Activity of CYP450 3A4 decreases and CYP450 2E1 activity increases. Obesity can increase renal clearance caused by higher cardiac output. It can also lead to kidney disease resulting in lower GFR.
Pharmacodynamics	Disparities in receptor expression and affinity. Excessive adipose tissue increases intrinsic insulin cleaving activity, leading to increase insulin requirements. Increased tumor necrosis factor-α, increases insulin resistance. Metabolic syndrome is related to high on-treatment platelet reactivity. Antiplatelet therapy should be tailored to each patient. Prasugrel and ticagrelor seems to have better platelet inhibition. Anticoagulants: difficult to determine optimal dose. Thromboembolism vs bleeding. DOACs do not have label indications on dose adjustment for body weight. Limited data on LMWH and unfractionated heparin. Beta-blocker therapies have a metabolism impact and weight gain. Reduction in resting and total energy expenditure, increased feelings of tiredness, decreased exercise tolerance, and nonexercise thermogenesis. Avoid metoprolol tartrate. HTN treatment: first line would be ACEI or angiotensin II receptor blocker.
Cardiac procedures
PCI	Difficult femoral access and hemostasis. Radial arterial access is preferred. Higher risk of stent thrombosis, especially after bare-metal stent implantation.
Open heart surgery	Higher CVD mortality in BMI ≥35 kg/m². Higher AF events. Increased risk of wound infection resulting from larger incisions, decreased blood supply within the adipose tissue and less sternal blood supply caused by bilateral use of the internal mammary artery. Increased risk for mediastinitis, acute renal failure, prolonged ventilation, pneumonia, and VTE.
Surgical peripheral revascularization	Increased risk for wound complications, surgical site infections, graft failure, and sepsis.
Valvular replacement	Higher risk for patient-prosthesis mismatch when body surface area is used.
Heart transplantation	High risk for rejection.
Therapeutic measures	May lead to weight gain or make weight loss more difficult.
Smoking cessation	Weight gain leads to reduced glycemic control. People with diabetes who quit smoking may need closer metabolic follow-up.
Insulin therapy	The anabolic effect of insulin leads to an increase in truncal fat mass. It increases energy intake linked to a fear of hypoglycemia. Reduction in glycosuria, central effects on weight, and appetite regulation. Insulin therapy may generate hyperphagia and weight gain by reducing hypothalamic (arcuate nucleus) signaling and increasing anabolic peptides like neuropeptide Y and Agouti-related peptide. Insulin detemir is associated with least weight gain.
Beta-blockers	Insulin resistance and increased risk of developing T2DM. Other effects mentioned above.
VADs	Significant weight gain after implantation.
Bidirectional relationship
Antidepressants	Depression has a strong relationship with obesity and some forms of CVD. At the same time, antidepressant therapy may promote weight gain.
Physical activity	PA is effective in the prevention of overweight and obesity, and also plays a key role in their treatment. Physical limitations and lack of adherence may worsen negative feedback.
CVD	Obesity is a main risk factor for developing CVD, but at the same time, CVD may be a limiting factor to weight loss. Not only for the detrimental effects of CVD but also for the side effects of therapeutic measures on weight management.

Multiple complications are associated with treatment, lifestyle options and cardiac procedures when managing CVD in people with obesity, with some aspects of management having a bidirectional relationship that can either exacerbate or improve CVD, obesity, and associated comorbidities.^23–40
ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; BMI = body mass index; CVD = cardiovascular disease; CYP450 = cytochrome P450; DOAC = direct oral anticoagulants; GFR = glomerular filtration rate; HTN = hypertension; LMWH = low molecular weight heparin; OSA = obstructive sleep apnea PCI = percutaneous intervention; T2DM = type 2 diabetes mellitus; VAD = ventricular assist device; VTE = venous thromboembolism.

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Challenges in Cardiovascular Evaluation and Management of Obese Patients

JACC State-of-the-Art Review

Abstract and Introduction

Abstract

Introduction

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar

Highlights

Figure 1.

Figure 1.

Central Illustration.

Central Illustration.

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