Table 2.
Summary of EPWG deliberations regarding full range of possible endpoints
| Endpoint | Relationship to obesity |
Clinical gravitas |
Related to ASCVD? | Susceptibility to ascertainment bias in an unblinded trial |
Acceptability to stakeholders and audience |
|---|---|---|---|---|---|
| All-cause mortality | Yes, BMI → mortality |
++++ | Only to the extent that cancer and other non-CVD deaths are influenced by underlying CVD. |
Minimal to none | Widely accepted as a secondary endpoint. |
| Hospitalized angina | Yes, BMI → CVD |
+++ | Yes, strongly | Yes. LSI staff and/or PCPs react to exercise-induced symptoms. |
Difficulty in adjudication and concerns reascertainment bias have discouraged wider use. |
| Urgent revascularization |
Yes, BMI → CVD | +++ | Yes, strongly | Possibly. LSI staff and/or PCPs may react to exercise- induced symptoms |
Concerns about ascertainment bias have traditionally discouraged experts in unblinded trials |
| Hospitalized CHF | Yes, BMI → CVD → CHF; BMI → BP → CHF; and BMI → Hypo- ventilation → RHF: and BMI → hyperglycemia → TZD → CHF |
+++ | Yes, but also related to non-ASCVD causes. But COPD and pneumonia – sometimes mistaken for CHF – are unrelated to CVD |
Possibly. LSI staff and/ or PCPs react to exercise- induced symptoms |
Difficulty in adjudication and complexity of underlying causes have traditionally discouraged experts. But pro-BNP now eases distinction from COPD and pneumonia |
| Incident CKD (stage 3/4) |
Yes, BMI → BP → CKD; And BMI → hyperglycemia → CKD |
++ | Yes, insofar as CKD is a strong risk factor for CVD and vice versa and they share many upstream risk factors |
Minimal, since periodic ‘gold standard’ assessments of CKD are conducted per study protocol. Some concerns about classification bias across ethnic groups |
Endpoints based on serum creatinine (e.g., doubling) are widely used as primary endpoint in trials of CKD prevention. Not commonly used in CVD trials. Variability and threshold effects raise concerns |
| Obesity-related cancer |
Yes, BMI → several obesity- related cancers. But, no evidence that weight loss improves mediating factors |
+ to +++ | No | Minimal to none | Combining cancer with CVD endpoints would be unusual, since the causal pathways are different |
| Incident LVH | Yes, BMI → BP → LVH |
++ | Yes | Minimal to none | Commonly used as a surrogate but not commonly combined with clinical endpoints. A variety of conflicting ECG definitions raises concerns |
| DVT/PE | Yes, BMI → DVT and DVT → PE |
+ to +++ | Thrombosis, yes; atherosclerosis, no |
Possibly. LSI staff and/ or PCPs react to exercise- induced symptoms |
Not commonly used. DVT occurrence often does not affect long-term prognosis |
| Fractures | Yes, but inverse: MI → fewer fractures |
+ to +++ | No | Minimal to none | Inverse relation inappropriate for primary endpoint |
BMI: body mass index; LSI: lifestyle intervention; BP: blood pressure; LVH: left ventricular hypertrophy; CKD: chronic kidney disease; ECG: electrocardiogram; CHF: congestive heart failure; PE: pulmonary embolism; CVD: cardiovascular disease; TZD: thiazolidinedione; DVT: deep venous thrombosis; PCP: primary care provider; ASCVD: atherosclerotic cardiovascular disease; RHF: right heart failure; COPD: chronic obstructive pulmonary disease; BNP: brain natriuretic peptide.