The Obesity Paradox in Patients With Peripheral Arterial Disease

Abstract

of lowering LDL-C with statins alone vs statins plus ezetimibe on common CIMT in patients with type 2 diabetes and no known prior cardiovascular events. The SANDS Trial was a randomized, open labeled, blinded to outcomes, 3-year trial examining the effects of aggressive goals for LDL-C (Յ70 mg/dL) non-high-density lipoprotein cholesterol (Ͻ100 mg/dL) and blood pressure (Ͻ115/75 mm Hg) reduction vs standard goals of Ͻ100 mg/dL, Ͻ130mg/dL, and Ͻ130/80 mm Hg, respectively, in 499 Native American patients with type 2 diabetes. The primary outcome was change in CIMT after 36 months of treatment.Ezetimibe is an antihyperlipidemic medication used to lower cholesterol levels. It acts by decreasing cholesterol absorption in the intestine and can be used alone or with other cholesterol-lowering medications. It is generally indicated for use when cholesterol levels cannot be controlled with statins alone.The authors compared CIMT levels for 36 months in diabetic individuals aged Ͼ40 years receiving statins plus ezetimibe vs statins alone. The CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups. LDL-C was reduced by 31 mg/dL (range, 23-37 mg/dL) and 32 mg/dL (range, 27-38 mg/dL) in the aggressive group by statins plus ezetimibe and statins alone, respectively. This was compared with changes of 1 mg/dL (range Ϫ3 to 6 mg/dL) in the standard group vs both aggressive subgroups (P Ͻ .0001). Within the aggressive group, mean CIMT at 36 months regressed in the ezetimibe and nonezetimibe subgroups but progressed in the standard treatment arm (Ϫ0.025, Ϫ0.012, and 0.039 mm, respectively; P Ͻ .0001).Comment: CIMT is considered a marker of future cardiovascular risk and thus can serve as a short-term surrogate for potential long-term cardiovascular events. The current trial has, therefore, two potential significant implications. The first is that ezetimibe does not provide any advantage over a statin alone in reducing long-term cardiovascular risk. The results would therefore seem to confirm the Enhanced Trial (N Engl J Med 2008;358: 1431-43) of 720 patients with familial hypercholesterolemia where there was no statistically significant difference in the primary end point of mean increase in CIMT over 24 months in the patients treated with statins alone vs statin plus ezetimibe. The second point is that it does appear possible to actually reduce surrogate markers of future atherosclerosis by aggressively lowering cholesterol beyond standard target levels. In its early stages, atherosclerosis may be a reversible disease.

The prognostic impact of general and abdominal obesity in peripheral arterial disease

“…More recently, Barba et al 23 observed that PAD patients showed an inverse relationship between BMI and cardiovascular mortality, which is consistent with the so-called obesity paradox that has been observed in subjects with multiple atherosclerotic risk factors, patients with heart failure, and those with coronary artery disease. 7,8,38 Consistently, in a non-homogeneous population of 2302 patients who underwent major vascular surgery (lower-limb revascularization procedures, carotid endarterectomy or abdominal aortic surgery), Galal et al 24 found that the higher the BMI, the lower the mortality rate. However, when the authors adjusted for the presence of chronic obstructive pulmonary disease, the inverse relationship was lost.…”

“…Nevertheless, very few studies have investigated the relationship between obesity and occurrence of cardiovascular events in PAD; moreover, with conflicting results. [21][22][23][24] This prompted us to conduct a prospective study aimed at evaluating the prognostic impact of obesity in a homogeneous cohort of PAD patients. Furthermore, as no study of obesity in PAD investigated the joint and independent effects of general and abdominal obesity, the secondary aim of our study was to compare the predictive value of BMI (an index of general obesity) and WC (an index of abdominal obesity).…”

Body Composition and Coronary Heart Disease Mortality—An Obesity or a Lean Paradox?

“…34 Even in patients with peripheral arterial disease, in whom smoking may be a more powerful risk factor than for CHD, chronic lung disease did not explain the obesity paradox, and in our cohort, COPD did not appear to be an independent predictor of mortality or to impact the independent role of BMI and BF on mortality. 24,34 In our study population, high mortality was confined to the population with low BF and low BMI. Although our population with high BF and low BMI was small (n=26), which makes mortality assessment difficult, the group with low BF and high BMI (n=125) also had low mortality, similar to the group with both high BF and high BMI (n=311).…”

The risk of general and abdominal adiposity in the occurrence of new vascular events and mortality in patients with various manifestations of vascular disease

“…25 Although obesity altered the risk for vascular mortality and all-cause mortality in CAD and PAD patients, no relationship between obesity and mortality was observed in CVD patients. The fact that there was no relationship between obesity and ischaemic stroke in these patients is an interesting finding, as recurrent stroke prevention guidelines state that weight reduction may be considered for all overweight ischaemic stroke and TIA patients to maintain the goal of a BMI between 18.5 and 24.9 kg m À2 .…”