Understanding Confounding in Cohort Studies
The correct answer is B: DM, HTN, and smoking are confounders. When the relative risk decreased from 2.8 to 1.8 after adjusting for these variables, this demonstrates classic confounding—these factors were associated with both the exposure (obesity) and the outcome (CVD), inflating the initial crude association 1.
Why This Represents Confounding
The Mechanism of Confounding
- Hypertension, diabetes, and smoking are strongly associated with obesity and independently increase cardiovascular disease risk, creating a confounded relationship 1.
- Among U.S. adults with hypertension, 49.5% are obese, 27.2% have diabetes, and 15.5% are current smokers, demonstrating the clustering of these risk factors 1.
- The initial RR of 2.8 included the combined effect of obesity plus these confounders, while the adjusted RR of 1.8 represents the independent effect of obesity alone 1.
Evidence of Risk Factor Clustering
- CVD risk factors frequently occur in combination, with ≥3 risk factors present in 17% of patients, and these factors share pathophysiological mechanisms including renin-angiotensin-aldosterone system activation and endothelial dysfunction 1.
- In NHANES data, 35.7% of obese individuals have hypertension, and 71% of adults with diabetes have hypertension, confirming the interdependence of these conditions 1.
- The relationship between obesity and CVD is mediated through metabolic, inflammatory, and hormonal changes that overlap with diabetes and hypertension pathways 1.
Why the Other Options Are Incorrect
Option A: "Adjustment Increased Likelihood of CVD"
- This is backwards—adjustment for confounders reduced the RR from 2.8 to 1.8, meaning it decreased (not increased) the apparent association between obesity and CVD 1.
- The adjustment removed the excess risk attributable to HTN, DM, and smoking, revealing obesity's true independent effect 1.
Option C: "The Initial RR is Inaccurate"
- The initial RR of 2.8 is not inaccurate—it is simply unadjusted and represents the total association including confounding 1.
- Both the crude (2.8) and adjusted (1.8) RRs are valid measures answering different questions: total association versus independent effect 1.
- The crude RR accurately reflects real-world risk for obese individuals who typically have multiple comorbidities 1, 2.
Clinical Implications
Understanding the Residual Risk
- Even after adjustment, obesity maintains an independent RR of 1.8 for CVD, confirming it as a true risk factor beyond its association with other conditions 1.
- The 47 million U.S. adults with metabolic syndrome (≥3 risk factors including abdominal obesity) face heightened CVD risk requiring comprehensive intervention 3.
Practical Application
- When assessing CVD risk in obese patients, clinicians must evaluate all clustered risk factors including blood pressure, glucose, and smoking status 1.
- The presence of multiple CVD risk factors results in high absolute risks—among hypertensive adults, 41.7% have 10-year CHD risk >20% 1.
- Treatment strategies must address global risk factor burden, as treating modifiable risk factors may reduce blood pressure through shared pathophysiology 1.
Common Pitfall to Avoid
- Do not interpret the adjusted RR as the "only" relevant measure—the crude RR reflects the total burden obese patients face in clinical practice, while the adjusted RR isolates obesity's independent contribution 1, 2.
- Recognize that diabetes and hypertension show synergistic additive interaction on coronary heart disease (SI 1.43), meaning their combined effect exceeds simple addition 2.