Causes: Deeper Dive into Comorbidities of HF

Reviewed by: HU Medical Review Board | Last reviewed: October 2019

Comorbidity is the presence of two or more chronic diseases, illnesses, or conditions in one person. They can impact health outcomes, require more complex clinical management, and result in higher health care costs.1

Comorbidities are frequently present in people with chronic heart failure (CHF). These other medical conditions can affect the quality of life, daily functioning, and likely have an effect on morbidity and mortality. Specific conditions are known to have an effect on heart failure and also the reverse, where heart failure can impact the management of other preexisting medical conditions.


Obesity, a common problem in the US, can cause the heart to have to work harder than for someone of normal weight. Elevated levels of cholesterol and blood pressure can cause the development of HF. Being overweight can also interfere with breathing at night and be a cause of sleep apnea, which is also related to heart failure.9


Diabetes and other metabolic disorders can increase the risk of developing heart failure. Diabetics often have hypertension and atherosclerosis (hardening of the arteries), both of which have been linked to heart failure. In 2016, around 26 million American adults had a diabetes diagnosis, which is close to 10% of the population. Race and gender have demonstrated influence on diabetes as well as heart failure. Prevalence is higher in both men and women of black and Hispanic heritage as compared to white men and women.2

Severe lung disease

If there is damage or a decrease in lung function, it can cause the heart to work harder to pump the oxygenated blood out to the body. HF and lung disease are common comorbidities in the elderly. Many people with HF also have lung conditions which can increase the risk of hospitalization and death. Clinical management of the two conditions requires coordination from the health care team to assure the best balance of symptom management.3

Cancer treatment

Certain cancer treatments are known to increase the risk of developing heart failure. For those that have been treated for breast cancer or lymphoma, treatments such as chemotherapy, radiation of the chest, immunotherapy, and some targeted therapies have led to the development of HF and vascular problems.4 Longer survival rates after cancer have led to long-term cardiac effects from the associated treatments. According to the National Cancer Institute, there is an increased need to evaluate short and long-term effects of cancer treatment on the heart.4

Amyloid heart failure

Amyloid heart failure is an underdiagnosed and potentially fatal disease. Its symptoms mimic other more common conditions.5 It develops when deposits of amyloid protein fibrils (thin fibers) accumulate in the walls of the left ventricle, the main pumping chamber of the heart. There are two kinds of amyloid HF: Transthyretin Amyloid cardiomyopathy (ATTR) and AL amyloid cardiomyopathy.5


Transthyretin is a transport protein. Made in the liver, it carries the thyroid hormone thyroxine and Vitamin A (retinol) through the body. When the transthyretin doesn’t form correctly, the abnormal misfolded proteins clump together to form amyloid fibrils. The amyloid protein deposits make the walls of the heart stiffer. This makes it more difficult for the left ventricle to both relax and refill with blood as well as to effectively pump blood out of the heart.6

There are two types of ATTR. Hereditary ATTR is caused by a mutation in the transthyretin gene, which produces amyloid deposits in the heart and other areas. It runs in families and can have an early onset around age 20 or appear as late as age 80.7 Wild-type ATTR usually develops after age 65 when with age, the normal TTR protein becomes unstable, misfolds, and forms amyloid fibrils. It not only affects the heart but can cause carpal tunnel syndrome and peripheral neuropathy (pain, tingling, and numbness in the hands and feet).6-7

AL amyloid cardiomyopathy

AL amyloid cardiomyopathy is a disease of the bone marrow. Abnormal antibodies produced in the bone marrow can be deposited in any tissue and cannot be broken down. These clumped proteins, called fibrils, interfere with normal body functions. Chemotherapy typically used to treat multiple myeloma is often used to treat AL amyloidosis; it attacks the abnormal cells that produce amyloid.5

There is no standard treatment for amyloidosis but there are new drugs in development including a treatment designed to remove the fibrils. In addition to drugs designed to address the abnormal proteins, treatment for cardiac symptoms is targeted towards managing fluid retention with diuretics and diet (salt restriction), and regulation ofheart rhythms (arrhythmias).8

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