This article was written in collaboration with Dr. Chip Lavie, MD.
Medical Director, Cardiac Rehabilitation and Prevention Director, Stress Testing Laboratory.
FITNESS AND FATNESS: HOW EXCESS FAT CAN AFFECT YOUR HEART.
The Obesity pandemic is well established with >70% of US adults being overweight (BMI >25) or obese (BMI >30) or severely obese (BMI >40). Obesity contributes directly to cardiovascular risk factors, including type 2 diabetes, hypertension, abnormal lipids, and sleep apnea. Obesity leads also to cardiovascular disease and cardiac mortality independently of other risk factors. Obesity is associated with coronary artery disease, heart failure, and cardiac arrhythmias including atrial fibrillation and sudden cardiac death.
How excess fat can cause Coronary Artery Disease (CAD).
It is not so much about the amount of excess weight that leads to cardiovascular disease but whether abdominal obesity is present. It is the presence of abdominal or visceral obesity that leads to cardiometabolic disease manifested as hypertension, low HDL, high triglycerides, hyperglycemia, and inflammation. A typical case would be a sedentary, middle-aged man with a BMI of 28 and a waist circumference of >40 inches (>35 in women). Very often, people may have undergone an ultrasound of the abdomen showing the presence of nonalcoholic fatty liver. Obesity and in particular visceral obesity accelerates atherosclerosclerotic changes with thickening of the arterial wall and accumulation of fatty streaks within these walls through insulin resistance and systemic and vascular inflammation. This metabolic syndrome can alter the function of the inner portion of the arterial wall, the endothelium, and decrease the bioavailability of nitric oxide, fundamental to atherosclerosis progression.
Clinical studies of patients with coronary artery disease revealed that at each level of BMI, higher measures of central adiposity were associated with a greater risk of CAD and cardiovascular mortality. Also important are the degree and duration of obesity which are strong predictors of CAD events. Some of the associations between overweight and obesity and CAD are attributed in part to HTN, lipid, and glucose abnormalities. Most patients will develop significant blockages in their coronary arteries that will produce reduced blood flow to the heart muscle and manifest as angina or myocardial infarction. Some patients may develop abnormalities in the coronary microvasculature, also a key regulator of coronary blood flow. These patients can have symptoms of angina and be taken to the cath lab with a coronary angiogram showing normal epicardial coronaries. Endothelial dysfunction and small vessel remodeling are independently associated with increased BMI.
How excess fat can cause Heart Failure.
Obesity can cause changes in cardiac function both directly in the heart muscle and blood vessels and indirectly through obesity-related comorbidities. The excess fat accumulation can lead to increased circulating blood volume, decreased systemic vascular resistance, increased cardiac output, left ventricular enlargement with increased wall stress, and myocardial muscle mass (LVH) with abnormal diastolic function. Also, obesity can result in increased deposition of fat around the heart (epicardium) and in the myocardium causing subsequent fibrosis that can lead to diastolic heart failure or HFpEF.
Excessive fat accumulation in obesity can cause hypoventilation and sleep apnea, with hypoxia, the elevation of the pulmonary pressure, enlargement of the right ventricle, and increased interdependence between the RV and LV causing diastolic dysfunction and HFpEF.
Many studies have shown that obesity is a risk factor for heart failure. The Framingham study showed that for every 1 unit of BMI increase, there was an increase in heart failure by 5% in men and 7% in women. Low fitness has been associated with a higher risk of heart failure across all BMI categories and may play an important role in the association between heart failure and BMI. It is reported in the literature that patients with overweight or mild obesity have a less severe form of heart failure, have lower levels of BNP (brain natriuretic peptide), and have better clinical outcomes than those with normal weight and similar degrees of heart failure. The lower BNP is not well understood while the improved clinical outcome has been labeled “the Obesity Paradox“.
How excess fat can cause Sudden Death.
The association between sudden death and Obesity is significant. For every 5 unit increase in BMI, there is a 16% increase risk of sudden death. Visceral fat again may play an important role with fat accumulation around the heart in the epicardium being related to PVCs, Ventricular tachycardia, Ventricular fibrillation, and mortality from sudden cardiac death. Epicardial fat infiltration and subsequent fibrosis may be a substrate for lethal reentry arrhythmias. Obesity-related LVH, autonomic imbalance, and QT prolongation are other potential sudden death risk factors. Moreover, in the clinical settings, performing CPR in obese patients can be difficult with chest compressions not being as efficacious, airway protection being challenging and defibrillation success lower due to higher thoracic impedance. Severe obesity is associated with higher mortality after in-hospital cardiac arrest.
How excess fat can cause Atrial Fibrillation (AFib).
Obesity may account for 20% of all afib cases. For every 5 unit increase in BMI, there is a 30% increase in the risk of afib in the general population, a 10% increase in afib in the postoperative period, and a 13% increase in recurrent afib post afib ablation. In addition, the more severe the obesity, the more chance for the afib to remain persistent.
Experimental studies have demonstrated epicardial fat infiltration into the myocardial tissue resulting in conduction abnormalities that could favor the development of afib. In the clinical setting, patients with obesity have higher left atrial pressure and volumes leading to atrial remodeling and abnormal contraction. In addition, obesity-related co-morbidities like HTN, DM, and sleep apnea are all associated with afib.
How treatment of Obesity can affect Cardiovascular Outcomes.
The most important lifestyle recommendation is a daily regimen of moderate-intensity aerobic exercise (walking 30 mins). This usually leads to improvements in glucose tolerance and insulin levels. Even without much weight loss, regular exercise activity can reduce visceral obesity, improve metabolic syndrome and reduce the risk of CAD by 50% compared to sedentary patients with the same metabolic profile. Reduction in caloric intake can accomplish some weight loss reduction with most regimens when combined with exercise, producing an 8-10% weight reduction that can be maintained long term as long as the patient adheres to their exercise activities. Even more important, however, is that adherence to plant-based and Mediterranean diets has been consistently associated with a lower risk of all-cause mortality. It also makes sense to limit sugar-sweetened beverages since their consumption is related to insulin resistance, abdominal obesity, and mortality.
Medical therapy for obesity has evolved tremendously in the last decade. Liraglutide, a first-generation GLP1 receptor agonist, has been shown to produce an average weight loss of 6% in patients with obesity. In patients with T2DM, liraglutide is effective in reducing cardiovascular events but data is lacking in obese patients without diabetes. Lorcaserin, as well as Naltrexone SR/Bupropion SR, are safe but data is lacking regarding cardiovascular outcomes. Even more interesting is the advent of the second generation of GLP1 agonists such as semaglutide. When combined with lifestyle modification, these drugs can produce a 10-15% weight loss.
The SELECT study of semaglutide 2.4 mg sc weekly vs placebo in non-diabetics with Obesity started enrolling patients >45 yo with BMI >27 with established CVD (prior MI or CVA, or PVD) in 2018 and will complete enrollment in 2023. Overall, >17,000 patients will be included and monitored for CV death, non-fatal MI, or non-fatal stroke. Surgical treatment for Obesity is considered the gold standard with average weight loss between 25-35%. Bariatric surgery is associated with a lower incidence of cardiovascular disease driven mainly by a lower incidence of myocardial infarction, unstable angina, coronary stents, or CABG.
Treatment of Cardiovascular Disease in Patients with Obesity
Patients with severe obesity have more complications after undergoing a coronary stenting procedure. There is more contrast-induced nephropathy requiring dialysis and more femoral vascular complications due to difficult access. In the APPROACH registry, the 5- and 10-year mortality was higher in the patients with BMI >40 and high-risk anatomy. The same applies to patients with severe obesity undergoing CABG with more postoperative complications such as post-op afib, prolonged mechanical ventilation, respiratory failure, renal failure requiring replacement therapy, sternal wound, and saphenous vein harvest site infections as well as long-term mortality.
In patients with obesity and heart failure, losing weight and increasing exercise activity can reduce symptoms of dyspnea, and improve exercise tolerance and quality of life as well as other conditions such as sleep apnea or other metabolic disorders. A higher level of fitness can prevent the recurrence of heart failure and improve prognosis. In obese patients and HFrEF, SGLT2 inhibitors such as dapagliflozin have been shown to reduce worsening heart failure or cardiovascular death. The most frequent cause of heart failure in Obese patients is HFpEF and SGLT2 inhibitors and mineralocorticoid antagonists have been beneficial in that setting reducing excess water retention, improving dyspnea, and reducing hospital admission for heart failure.
In patients with obesity and atrial fibrillation, losing weight as well as cardiometabolic risk factor management results in a greater reduction in afib burden and severity. When this approach was implemented post afib ablation, it resulted in a 5-fold increase in freedom from afib even up to five years in patients who lost >10% of their weight.