Obesity and Peripheral Artery Disease: Current Evidence and Controversies

Abstract

Purpose of Review Obesity is a significant public health problem and a major risk factor for the development and progression of atherosclerosis and its cardiovascular manifestations. Lower extremity peripheral artery disease (PAD) affects 3%–10% of the Western population and, if left untreated, can lead to devastating outcomes with both an increased risk of morbidity and mortality. Interestingly, the association between obesity and PAD remains debatable. Whereas it is well known that PAD and obesity frequently overlap in the same patients, many studies have demonstrated a negative association between obesity and PAD and a protective effect of obesity on disease development and progression, a phenomenon described as the “obesity paradox.” Possible mechanisms for this paradox may include genetic background, as assessed by mendelian randomization studies, adipose tissue dysfunction, and body fat distribution rather than adiposity, while other factors, such as sex, ethnicity, sarcopenia in the elderly population, or aggressive treatment of co-existing metabolic conditions in individuals with obesity compared to those with normal weight, could have some impact as well. Recent Rindings Few reviews and meta-analyses examining systematically the relationship between obesity and PAD exist. The impact of PAD development due to the presence of obesity remains largely controversial. However, the most current evidence, backed by a recent meta-analysis, suggests a potential protective role of a higher body mass index on PAD-related complications and mortality. Summary In this review, we discuss the association between obesity and PAD development, progression, and management, and the potential pathophysiologic mechanisms linking the two diseases.

Association of body mass index and blood pressure variability with 10-year mortality and renal disease progression in type 2 diabetes

“…We studied baseline rather than the mean BMI during the study period in order to minimise the possibility of reverse causality, namely that cardiac disease or malignancy leads to weight loss. The association of a higher BMI with lower cardiovascular [ 39 – 42 ] and cancer [ 43 – 45 ] mortality has been previously reported and is often referred to as the obesity paradox. The reasons for this are unclear, given the known association of adiposity with adverse outcomes [ 46 ].…”

Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study

“…Previous observational studies have uncovered a potential positive correlation between obesity and PAD. However, some studies have also raised the concept of the “obesity paradox” ( 6 ), which has spurred researchers to seek more evidence in order to establish a causal relationship between the two. An MR study conducted within the UK Biobank, involving 367,703 participants, has indicated that a higher BMI, particularly with a focus on the fat mass index, is associated with an elevated risk of several cardiovascular diseases, including PAD ( 26 ).…”

“…An earlier systematic study conducted among Hispanics found that despite a higher prevalence of risk factors such as hypertension, obesity, and diabetes when compared to non-Hispanic whites, Hispanics displayed notably lower rates of PAD and carotid artery disease, suggesting the existence of an “obesity paradox” within the Hispanic population ( 29 ). Simultaneously, multiple studies have suggested that individuals of African descent might exhibit a heightened susceptibility to PAD ( 1 , 6 , 30 , 31 ). These findings imply the presence of racial disparities in the causal relationship between obesity and PAD, emphasizing the significance of studying diverse ethnic groups in our future research.…”

“…Obesity is a state characterized by an excess accumulation of body fat, typically resulting in a substantial deviation from the normal weight range, with obesity defined ( 6 ) as a body mass index (BMI) of ≥30 kg/m 2 . Obesity can have a significant impact on health, making individuals susceptible to various complications, including metabolic syndrome, type 2 diabetes, joint issues, specific cancers, as well as a range of cardiovascular diseases, including coronary artery disease (CAD) and potential PAD ( 6 ). Numerous studies in the past have explored the connection between obesity and PAD.…”

The parallel lives of pandemics: COVID‑19 and obesity

“…Both COVID-19 and obesity are influenced by the same pre-existing health conditions and risk factors, such as an advanced age, a deteriorated socio-economic status and co-existing health conditions ( 2 , 11-15 ). Comorbidities, such as type 2 diabetes mellitus and cardiovascular disorders, as well as cancer, are typically the result of obesity, which contribute to unfavorable COVID-19 outcomes ( 2 , 16-20 ). Additionally, obesity influences the immune system, which has implications in the body's ability to defend against infections and, perhaps, the COVID-19 outcomes ( 20-22 ).…”