Obesity and Cardiovascular Health: From Pathophysiology to Comprehensive Intervention Strategies

Epidemiological surveys worldwide show that obesity not only affects physical appearance but is also a significant risk factor for most chronic diseases, including cardiovascular disease, diabetes, and cancer. It even shares a common pathophysiological basis with various chronic diseases. In 2016, the American Association of Clinical Endocrinology (AACE) first proposed renaming obesity as obesity-based chronic disease (ABCD), conceptualizing obesity as a chronic disease state leading to a variety of complications characterized by obesity. This includes a specific medical diagnostic term reflecting the pathophysiological processes underlying various diseases, including cardiovascular disease, endocrine and metabolic disorders, and cancer. I. Overview Cardiovascular disease, including heart and vascular diseases, is the leading cause of disability and death worldwide, seriously threatening human health. In 2016, cardiovascular disease ranked first among causes of death for urban and rural residents in my country, accounting for more than 40% of all deaths, higher than cancer and other diseases. The "China Cardiovascular Disease Report 2018" shows that the prevalence of cardiovascular diseases in my country is on the rise, with an estimated 290 million people currently suffering from cardiovascular diseases, including 13 million with stroke, 11 million with coronary heart disease, and 245 million with hypertension. Reducing the incidence, disability, and mortality rates of cardiovascular diseases has become a major concern. Epidemiological data shows that obesity is not only a risk factor for cardiovascular disease but also promotes the accumulation of multiple cardiovascular metabolic risk factors, exacerbating cardiovascular and cerebrovascular damage. A cross-sectional survey of 240,000 adults in China showed that over 90% of obese individuals had hypertension and glucose and lipid metabolism disorders; those with abdominal obesity had a more than four times higher risk of developing hypertension than those with normal waist circumference. The 2013 US Adult Obesity and Overweight Management Guidelines state that a 3%–5% weight loss can lower blood glucose and triglyceride levels; a weight loss of ≥5% can reduce the risk of obesity-related diseases such as hypertension, coronary heart disease, and diabetes. Therefore, controlling obesity is of great significance in reducing the incidence of cardiovascular diseases. Against the backdrop of accelerating societal aging and urbanization, and the increasing prevalence of obesity and obesity-related diseases, my country faces a severe situation of rapidly rising cardiovascular disease incidence and mortality rates, which will inevitably pose a serious threat to the health of Chinese residents and impose a heavy disease burden on society. Given my country's national conditions, actively carrying out the prevention and treatment of cardiovascular diseases is crucial for maintaining the health of Chinese residents and sustaining economic development. II. Pathophysiological Changes

The mechanisms by which obesity leads to hypertension are complex, involving factors such as sympathetic hyperactivity, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and insulin resistance. The main pathophysiological mechanisms involve activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, increased cardiac output, sodium and water retention and increased blood volume, insulin resistance, adipokines imbalance, and sleep apnea syndrome. These factors act on the cardiovascular system in different ways, leading to elevated blood pressure. The main pathological changes in hypertension are arterial lesions and left ventricular hypertrophy.

The main cause of coronary heart disease (CHD) is coronary atherosclerosis, which leads to obstruction or narrowing of the coronary arteries, sometimes accompanied by coronary artery spasm, resulting in myocardial ischemia and hypoxia. Obesity is a multifactorial chronic disease characterized by subcutaneous and visceral fat accumulation, playing a significant role in the occurrence and development of atherosclerosis. The mechanisms by which obesity leads to atherosclerosis include insulin resistance, abnormal lipid metabolism, adipokines imbalance, oxidative stress, immune inflammatory response, endothelial dysfunction, impaired autophagy, and changes in gut microbiota, all of which are considered to be related to atherosclerosis.

Obesity is an independent risk factor for stroke. Obese patients are in a state of chronic mild inflammation, which can trigger oxidative stress, insulin resistance, metabolic disorders such as blood glucose, blood lipids, and blood pressure disturbances, and vascular endothelial dysfunction, thus promoting cerebrovascular events. In addition, obese patients are prone to sleep apnea syndrome and hyperhomocysteinemia, which are also risk factors for stroke. III. Clinical Manifestations

Hypertension and obesity often coexist. Most patients with hypertension have an insidious onset, with few or no symptoms, and the condition is often discovered during physical examinations or when seeking medical attention for other illnesses. Some patients may experience dizziness, headache, palpitations, and a throbbing sensation in the temporal region; others may present with neurological symptoms such as tinnitus, mood swings, poor concentration, and insomnia. In the early stages of the disease, blood pressure fluctuates and may temporarily rise. This temporary increase is related to emotional excitement, stress, anxiety, and strenuous exercise, and blood pressure usually returns to normal after rest or removal of the triggering factor. As the disease progresses, blood pressure gradually becomes persistently elevated. While changes in mental and emotional state can further increase blood pressure, removing the triggering factor does not restore it to normal. In the later stages of the disease, target organs such as the heart, brain, and kidneys may be damaged, resulting in corresponding target organ symptoms.

Coronary artery disease (CAD) presents with varying clinical characteristics depending on the location of the coronary artery lesions, the extent of blood supply, the degree of narrowing, and the rate of progression of myocardial ischemia. Most patients are asymptomatic in the early stages, but symptoms develop as the condition worsens. The most common symptoms are angina and shortness of breath. Angina is often triggered by physical activity or emotional stress, manifesting as sudden, suffocating or squeezing pain in the precordial region. The pain typically begins behind the sternum or in the precordial area and radiates upwards to the ulnar side of the left upper limb, and may also radiate to the jaw. It is often relieved by rest or sublingual nitroglycerin. Some patients experience atypical symptoms, such as precordial discomfort, palpitations, or fatigue, or primarily gastrointestinal symptoms. In cases of myocardial infarction, the chest pain is severe, prolonged, and unrelieved by nitroglycerin. It may be accompanied by nausea, vomiting, sweating, fever, and even cyanosis, decreased blood pressure, shock, and heart failure.

Different types of stroke present with varying clinical manifestations. Generally, it is characterized by sudden onset, with rapid development of focal or diffuse brain dysfunction, such as changes in speech, vision, gait, or comprehension, or a sudden onset of severe headache. The most common symptoms are unilateral facial numbness or drooping of the mouth, slurred speech or difficulty understanding, fixed gaze to one side, or sudden weakness, clumsiness, heaviness, or numbness in one side of the body (with or without facial involvement). Other symptoms include sudden onset of facial drooping, hemiplegia; difficulty seeing in one or both eyes; unsteady gait, dizziness, loss of balance or coordination; severe headache and vomiting (unusual in the past); confusion or seizures, etc. IV. Treatment and Prognosis

Lifestyle interventions, including a balanced diet, moderate physical activity, changes in unhealthy lifestyle habits, and weight control, can not only reduce the incidence of cardiovascular disease but also improve the prognosis of patients who already have it. A light diet is recommended, rich in vitamins and dietary fiber, while limiting the intake of sucrose and sugary foods. Exercise should be moderate, consistent, and regular, choosing a long-term, regular, and gradual approach. Quitting smoking, limiting alcohol consumption, reducing stress, and maintaining mental balance are also important components of lifestyle interventions.

Drug therapy (1) Hypertension: There are five basic classes of antihypertensive drugs: diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). Studies have shown that ACEIs and ARBs not only have good antihypertensive effects, but also improve insulin resistance, improve glucose metabolism, and reduce fatty lesions, and can be used as first-line drugs for hypertension combined with obesity. Calcium channel blockers (CCBs) have no adverse effects on glucose and lipid metabolism, but no significant weight loss effect, and can be used as combination drugs for hypertension combined with obesity. Diuretics can reduce water and sodium retention and volume overload, but long-term high-dose use can cause hypokalemia, hyperuricemia, and glucose intolerance. Therefore, diuretics can be used in combination at low doses. Beta-blockers can antagonize the activation of the sympathetic nervous system, but long-term high-dose use may have adverse effects on glucose and lipid metabolism. Therefore, they can only be considered when combined with myocardial infarction, heart failure, or significant sympathetic hyperactivity. (2) Coronary artery disease: Drug therapy is the foundation of coronary artery disease control. When choosing treatment drugs, the first consideration should be the prevention of myocardial infarction and death, followed by reducing myocardial ischemia, relieving symptoms, and improving quality of life. Drugs mainly include antiplatelet therapy, anticoagulation, and anti-myocardial ischemia therapy. In addition, cardiovascular risk factors should be actively managed, including blood pressure control, lipid-lowering therapy, blood glucose management, and obesity management. If myocardial ischemia persists after drug therapy, coronary angiography should be performed to determine the severity of the lesion, and revascularization surgery should be considered. (3) Stroke: Stroke can be divided into hemorrhagic stroke and ischemic stroke. Different types of stroke require different treatments. Specific treatments include thrombolysis, antiplatelet therapy, early anticoagulation, and neuroprotection. Non-specific treatments include antihypertensive therapy, lipid-lowering therapy, blood glucose management, cerebral edema, and intracranial hypertension management. Since there is a lack of effective treatment for stroke, prevention is currently considered the best measure. Obesity, hypertension, hyperglycemia, and dyslipidemia are important controllable risk factors for stroke. Therefore, controlling risk factors such as obesity is particularly important for preventing the onset and recurrence of stroke. (4) Weight loss drugs: For obese patients who do not respond to lifestyle interventions, weight loss drugs and some hypoglycemic drugs that can reduce weight can be considered. Since most weight loss drugs have different degrees of adverse reactions in the neurological and cardiovascular systems, obese patients with cardiovascular disease should use them rationally under the guidance of a specialist to avoid adverse reactions.

Surgical treatment is crucial for managing cardiovascular disease risk factors. Obesity has become a global public health issue requiring timely intervention and treatment. When weight loss goals cannot be achieved through a combination of diet, exercise, and medication, surgical treatment can be used to address obesity. Surgery not only aids in weight loss but also improves manageable cardiovascular risk factors such as blood sugar, blood lipids, and blood pressure, making it an important means of improving cardiovascular disease prognosis. Percutaneous renal artery sympathetic ablation is primarily used to treat refractory hypertension. Surgical treatment for coronary artery disease patients mainly aims at coronary artery revascularization, including percutaneous coronary intervention and coronary artery bypass grafting.