Obesity and Cardiovascular Disease: Assessment and Treatment

Definition and pathophysiology

Obesity is a chronic, relapsing and biologically complex disease characterized by excessive accumulation of adipose tissue. It is an important cause of cardiovascular disease (CVD), cardiovascular risk-factor clustering, disability and premature mortality. Cardiovascular conditions associated with obesity include hypertension, dyslipidaemia, coronary artery disease (CAD), atherosclerosis, heart failure (HF), atrial fibrillation and cardiovascular events.

In clinical practice, obesity is conventionally defined by a body mass index (BMI) of ≥30 kg/m2. Severe obesity is generally defined as BMI ≥35 kg/m2, while BMI ≥50 kg/m2 has been termed super-morbid obesity. BMI categories are summarized below.

BMI is useful for screening and population-level risk estimation, but it does not characterize body composition, fat distribution, skeletal muscle mass, physical fitness or individual health status. In particular, it cannot distinguish adipose tissue from lean mass. Waist circumference and the waist-to-hip ratio provide additional information about visceral adiposity and may correlate more closely with outcomes than BMI, particularly in women.

For European populations, waist circumference above 94 cm in men or 80 cm in women is considered indicative of obesity or excess abdominal adiposity. Ethnic-specific thresholds are lower or otherwise modified in some populations.

Cardiometabolic mechanisms

Visceral and ectopic fat are particularly relevant to cardiovascular risk. Excess adipose tissue promotes:

• Chronic, low-grade systemic inflammation

• Insulin resistance

• Abnormal adipokine signalling

• Endothelial dysfunction

• Dyslipidaemia

• A prothrombotic state

• Albuminuria and declining estimated glomerular filtration rate

• Development of type 2 diabetes mellitus

• Atherosclerotic cardiovascular events

• HF and atrial fibrillation

Obesity therefore acts both as an independent cardiovascular risk factor and as a driver of hypertension, diabetes, dyslipidaemia and systemic inflammation. It is also associated with respiratory disorders, notably obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome, which further increase cardiovascular burden.

Obesity may be a particularly important cause of HF with preserved ejection fraction (HFpEF). Obese patients with HFpEF can have pathophysiological characteristics that differ from those of non-obese patients, and obesity complicates assessment of intravascular volume in both ambulatory and inpatient settings.

Clinical presentation and symptoms

Obesity itself may be asymptomatic, but its clinical expression is often determined by associated cardiovascular, respiratory, metabolic, musculoskeletal and psychological complications. Symptoms and conditions that should prompt assessment include:

• Hypertension

• Dyspnoea

• Exercise intolerance

• Congestive HF

• CAD

• Palpitations or suspected atrial fibrillation

• OSA or daytime symptoms suggestive of sleep-disordered breathing

• Hypoventilation

• Peripheral oedema or venous disease

• Reduced mobility

• Osteoarthritis and low back pain

• Symptoms of type 2 diabetes or metabolic syndrome

• Depression, low self-esteem or body-image disturbance

The number and severity of obesity-related complications generally increase as the degree of obesity rises. Nevertheless, BMI alone does not define an individual’s cardiovascular risk. Cardiorespiratory fitness, skeletal muscle mass and the distribution of adipose tissue materially influence prognosis.

Obesity and heart failure

Obesity increases the risk of HF and is common among patients with established HF, particularly HFpEF. Assessment of congestion may be difficult because physical findings and natriuretic peptide concentrations can be altered by adiposity.

An “obesity paradox” has been described in HF: overweight and mildly to moderately obese patients may have more favourable outcomes than leaner or underweight patients. This observation is complex and should not be interpreted as evidence that obesity is protective. The relationship is influenced by diabetes, body composition, skeletal muscle mass and cardiorespiratory fitness. The apparent paradox is not consistently observed in patients with diabetes, and obese patients with preserved muscle mass may fare better than obese patients with sarcopenia.

Evaluation and physical examination

All adults should be screened for obesity and offered intensive lifestyle counselling, including behavioural interventions intended to support sustained weight loss. Assessment should be structured around four domains:

• A focused history

• Anthropometric and physical examination

• Identification of complications and comorbidities

• Readiness and ability to engage in weight management

Obesity-focused history

The discussion should be conducted sensitively because terminology related to body weight can be experienced as stigmatizing. Neutral terms such as “weight,” “excess weight,” “BMI” or “unhealthy weight” may be preferable to pejorative language.

The history should explore:

• Factors contributing to weight gain

• The effect of weight on cardiovascular and general health

• Current and future risk associated with adiposity

• Difficulties encountered in weight management

• Patient-defined goals and expectations

• Motivation to begin treatment

• The type of support required

Dietary history should identify patterns involving refined grains, starches, sugars and processed meats, as well as opportunities to increase fruit, vegetables, nuts, fish, vegetable oils and whole grains. Physical activity, sedentary behaviour and fitness should be assessed independently of BMI because physical fitness is an important predictor of all-cause mortality.

Sleep assessment should address regularity, duration, efficiency and satisfaction. Sleep deprivation is associated with alterations in appetite regulation, sympathetic nervous system activity, insulin sensitivity and circadian rhythm. Stress and activation of the adrenal cortical axis may also contribute to weight gain and adverse eating behaviours.

Secondary and medication-related causes

Most obesity is promoted by interacting biopsychosocial and behavioural factors, but the history may suggest secondary causes requiring further evaluation. These include:

• Polycystic ovarian syndrome

• Hypothyroidism

• Cushing syndrome

• Hypothalamic disease

Medication-associated weight gain should also be considered. Reported medication classes include:

• Insulin, sulfonylureas and thiazolidinediones

• Steroid hormones

• Clozapine, olanzapine and risperidone

• Lithium

• Tricyclic antidepressants, monoamine oxidase inhibitors, paroxetine and mirtazapine

• Valproate, gabapentin and carbamazepine

Non-steroidal anti-inflammatory drugs and calcium-channel blockers may cause peripheral oedema, but the source material distinguishes this from an increase in body fat.

Anthropometry

Weight, height and BMI should be recorded at cardiovascular prevention visits. BMI is calculated as weight in kilograms divided by height in metres squared. Waist circumference should be measured as a surrogate for visceral adipose tissue, in the horizontal plane above the iliac crest, particularly in individuals with BMI ≤35 kg/m2.

Cardiorespiratory fitness should be considered alongside BMI and body composition. Peak oxygen consumption adjusted solely for total body weight may underestimate exercise capacity in obesity; adjustment for lean body mass is preferable for risk stratification.

Assessment of complications

The evaluation should be guided by symptoms, risk factors and clinical suspicion. Relevant cardiovascular and respiratory complications include:

• Hypertension

• CAD

• HF

• Atrial fibrillation

• Cor pulmonale

• Pulmonary embolism

• Dyspnoea

• OSA

• Obesity hypoventilation syndrome

• Asthma

Other associated conditions include type 2 diabetes, metabolic syndrome, dyslipidaemia, metabolic dysfunction-associated steatotic liver disease, osteoarthritis, venous disease, depression and impaired mobility.

Readiness to change

Treatment is more likely to be effective when aligned with the patient’s motivation, circumstances and expectations. Readiness assessment should consider:

• Desire and confidence to change

• Support systems

• Stressful life events

• Psychiatric status

• Time availability and practical constraints

• Appropriateness of treatment goals

Motivational interviewing can quantify both the perceived importance of weight management and confidence in undertaking it, using a 0-to-10 scale. Motivation and resistance should be considered as opposing forces that determine readiness.

Diagnostics and risk assessment

Comprehensive cardiovascular risk assessment should be considered in individuals with an unfavourable body composition. The principal risk-related consequences of adiposity include hypertension, dyslipidaemia, insulin resistance, inflammation, a prothrombotic state, albuminuria, reduced estimated glomerular filtration rate, type 2 diabetes, CVD events, HF and atrial fibrillation.

The source material does not provide specific electrocardiographic, echocardiographic, coronary imaging or electrophysiological protocols for obesity. Diagnostic testing should therefore be directed by the clinical presentation and suspected complications.

Functional and disease staging

BMI-based classification can be supplemented by obesity disease staging. One approach assigns:

• Stage 0: overweight or obesity without identified complications

• Stage 1: overweight or obesity with at least one mild-to-moderate complication

• Stage 2: overweight or obesity with at least one severe complication

Examples of complications include prediabetes, hepatic steatosis, metabolic syndrome, hypertension, type 2 diabetes, clinically important OSA and osteoarthritis. The Edmonton Obesity Staging System offers a separate framework based on medical, functional and psychological morbidity, independent of BMI.

Exercise assessment

A cardiovascular assessment is warranted before high-intensity exercise in obese individuals because associated diabetes, hypertension, dyslipidaemia, cardiovascular disease and respiratory disease may increase risk. Individuals with a normal cardiovascular assessment should not routinely be restricted from exercise.

Non-weight-bearing activities, such as cycling and swimming, may be advantageous when musculoskeletal loading is a concern. High-volume weight-bearing exercise on hard surfaces may reasonably be limited until substantial weight reduction has occurred. If very high exercise volumes are undertaken, adequate recovery time is important.

Biomarkers and laboratory findings

All patients undergoing obesity assessment should have:

• Fasting lipid profile, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides

• Chemistry panel

• Glycated haemoglobin

• Blood-pressure measurement

The broader metabolic and cardiovascular assessment may identify:

• Insulin resistance

• Type 2 diabetes

• Dyslipidaemia

• Systemic inflammation

• Albuminuria

• Reduced estimated glomerular filtration rate

Natriuretic peptide concentrations may be lower in obese patients with HF. This is attributed to increased expression of clearance receptors and enhanced peptide degradation by adipose tissue. Consequently, natriuretic peptide values must be interpreted in the context of body habitus and the overall clinical assessment.

Treatment and management

Obesity management should be comprehensive and directed both at weight reduction and at prevention or treatment of adiposity-related complications. Treatment options include lifestyle intervention, pharmacotherapy and metabolic/bariatric surgery. The intensity of treatment should reflect obesity stage, cardiovascular disease, comorbidities, functional impairment, patient goals and readiness.

Lifestyle and behavioural treatment

Lifestyle intervention should include dietary modification, regular physical activity and behavioural support. Dietary priorities include reducing refined grains, starches, sugars and processed meats while increasing fruits, vegetables, nuts, fish, vegetable oils and whole grains in the context of regular physical activity.

Weight reduction of 5% to 10% can improve:

• Blood pressure

• Triglyceride-rich lipoproteins

• Low-density lipoprotein cholesterol

• High-density lipoprotein cholesterol

• Glucose tolerance

• Insulin resistance

European recommendations describe a minimum of 150 minutes per week of moderate-intensity endurance exercise combined with three weekly resistance-training sessions. Exercise can reduce intra-abdominal fat, improve muscle and bone mass, attenuate the fall in resting energy expenditure associated with weight loss, and improve blood pressure, inflammation, glucose tolerance, insulin sensitivity, lipid profile, physical fitness, well-being and psychological health.

The effect of exercise alone on fat mass is modest. More than 225 minutes per week of endurance exercise may be required to maximize fat-mass loss in obese individuals. In people with hypertension, at least 30 minutes of moderate-to-vigorous dynamic aerobic activity on 5–7 days per week is recommended in the source material, with resistance training on 2–3 days per week as an additional blood-pressure-lowering strategy.

No specific dietary pattern has consistently demonstrated superiority for sustained weight reduction among motivated individuals. Intermittent fasting may provide clinical benefits even without substantial weight loss, although the source material does not specify a preferred fasting regimen.

Behavioural interventions have produced modest average weight loss and reduced weight regain compared with controls, but trials have not definitively established reductions in cardiovascular events or mortality. A major limitation has been difficulty maintaining weight loss over the long term.

Anti-obesity pharmacotherapy

Prompt anti-obesity pharmacotherapy is indicated for:

• BMI ≥30 kg/m2, or

• BMI ≥27 kg/m2 with a weight-related medical condition, such as type 2 diabetes, metabolic-associated liver disease, hypertension or CVD

Novel incretin-based agents have substantially expanded treatment options. Weekly injectable therapies cited in the source material include:

• Semaglutide 2.4 mg, associated with approximately 15% weight loss

• Tirzepatide 15 mg, associated with approximately 23% weight loss

GLP-1 receptor agonist therapy reduces appetite and promotes satiety. GLP-1 receptor activation stimulates glucose-dependent insulin release, suppresses glucagon secretion and delays gastric emptying. These agents may also have effects involving vascular inflammation, coagulation, blood pressure and renal function.

In people with type 2 diabetes, GLP-1 receptor agonists have been associated with relative reductions in several cardiovascular and renal outcomes, including myocardial infarction, stroke, hospitalization for HF, worsening renal function, cardiovascular mortality and all-cause mortality. In overweight individuals without diabetes, semaglutide has also been associated with cardiovascular event reduction and approximately 9% body-weight reduction in the cited outcome data.

Practical considerations include:

• Gastrointestinal adverse effects are common with semaglutide and other GLP-1 receptor agonists.

• Gallbladder disease may occur.

• The long-term effects of GLP-1 agonism remain incompletely defined.

• Possible loss of muscle mass in addition to adipose tissue is a continuing concern.

• Cost and equitable access are major limitations.

• Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/GLP-1 agonist, and oral GLP-1 receptor agonists are additional developing approaches, with cardiovascular endpoint evaluation ongoing.

The source material does not provide dose-escalation schedules, contraindications, treatment duration or detailed adverse-effect management.

Metabolic and bariatric surgery

Metabolic/bariatric surgery is considered safe and effective in patients meeting clinical criteria of:

• BMI >35 kg/m2, irrespective of associated obesity-related comorbidity under contemporary surgical guidance

• BMI >30 kg/m2 with a weight-related medical condition, particularly diabetes in the cited recommendations

Surgery may be particularly relevant for patients with severe obesity and CVD. Cardiovascular benefits may result from:

• Weight reduction

• Improved diabetes control

• Improved lipid profile

• Improved hypertension

• Reduced left ventricular hypertrophy and ventricular strain

• Improvement in sleep apnoea

• Reduced hepatic complications in patients with steatohepatitis

The source material reports observational evidence of lower long-term mortality and fewer incident cardiovascular outcomes after metabolic surgery, but also emphasizes that surgery carries risk and remains a limited and underused resource. Weight regain is recognized as an important issue, although detailed preventive or corrective strategies are not provided.

Guideline-based management principles

The guideline-based principles supported by the source material are:

• Screen all adults for obesity.

• Record weight, height, BMI and, when appropriate, waist circumference.

• Assess cardiovascular risk and obesity-related complications systematically.

• Provide intensive lifestyle counselling with behavioural intervention.

• Consider anti-obesity pharmacotherapy at BMI ≥30 kg/m2, or at BMI ≥27 kg/m2 when a weight-related medical condition is present.

• Consider metabolic/bariatric surgery at BMI >35 kg/m2, and in selected patients with BMI >30 kg/m2 and a weight-related condition.

• Combine endurance and resistance exercise.

• Assess cardiovascular status before high-intensity exercise.

• Treat obesity and its associated conditions as an integrated cardiovascular prevention strategy.

• Incorporate patient readiness, goals, psychological status, access and long-term adherence into treatment planning.

In patients with obesity and type 2 diabetes, weight reduction combined with increased daily physical activity and structured exercise is emphasized for improving metabolic control, exercise capacity and clinical outcomes. A Mediterranean diet supplemented with olive oil and/or nuts is associated with reduced major cardiovascular events in patients with CVD.

Prognosis and follow-up

Obesity is associated with increased morbidity, mortality, reduced quality of life and substantial healthcare burden. Cardiovascular risk generally rises with increasing BMI, but prognosis is also shaped by visceral adiposity, cardiorespiratory fitness, skeletal muscle mass, sarcopenia, diabetes and established cardiovascular disease.

The obesity paradox in HF and perioperative populations illustrates the limitations of BMI as a prognostic measure. Better fitness may be associated with more favourable prognosis regardless of body composition, whereas low cardiorespiratory fitness predicts mortality independently of BMI.

Follow-up should be longitudinal and should reassess:

• Body weight and BMI

• Waist circumference where appropriate

• Blood pressure

• Glycaemic status

• Lipid profile

• Renal function and albuminuria when clinically indicated

• Exercise capacity and physical activity

• Symptoms of HF, CAD, atrial fibrillation and sleep-disordered breathing

• Adherence, treatment response and adverse effects

• Psychological health and readiness to continue treatment

• Weight regain

Weight loss may improve quality of life and exercise capacity and may contribute to reverse ventricular remodelling in patients with HF, but its effect on survival in HF remains uncertain in the source material. Ongoing evaluation is therefore required even when weight reduction has been achieved, because obesity is chronic and relapsing and because cardiovascular risk depends on more than body weight alone.