Lee 2008: WHtR 0.5 Cutoff Meta-Analysis Validation

Background

Dr. Crystal Man Ying Lee and colleagues at the University of Sydney published this major meta-analysis in the International Journal of Obesity examining indices of abdominal obesity as predictors of cardiovascular disease. This study provided definitive evidence that central adiposity measures outperform BMI for cardiovascular risk prediction.

Study Design

Methodology:

• •Systematic review and meta-analysis
• •Literature search: 1966-2007
• •32 prospective cohort studies included
• •Total sample: >310,000 participants
• •Pooled analysis with study-level covariates

Outcomes:

• •Incident cardiovascular disease (MI, stroke, CV death)
• •Studies with ≥3 years follow-up
• •Comparison of WHtR, waist circumference, and BMI

Key Findings

Pooled Relative Risk for Cardiovascular Events:

Per 1 SD increase in each index:

Index	Men RR	Women RR
WHtR	1.40	1.53
WC	1.36	1.48
BMI	1.24	1.32

Critical Finding: Central adiposity measures (WHtR, WC) significantly outperformed BMI for CVD prediction. WHtR showed highest risk ratios.

Head-to-Head Comparisons

WHtR vs. BMI:

• •21 studies allowed direct comparison
• •WHtR superior in 17/21 studies (81%)
• •Pooled difference in AUROC: +0.04 (p<0.001)
• •Especially marked in lean populations

WHtR vs. WC:

• •15 studies allowed comparison
• •Similar discrimination (AUROC within 0.01)
• •WHtR advantage: simpler interpretation, height-adjusted

WC vs. BMI:

• •24 studies with comparison
• •WC superior in 20/24 studies (83%)
• •Central adiposity clearly outperforms total adiposity

Subgroup Analyses

By Sex:

• •Women showed stronger WHtR-CVD association (RR 1.53 vs. 1.40)
• •May reflect different fat distribution patterns
• •WHtR captured risk in both sexes effectively

By Age:

• •<55 years: WHtR RR 1.45
• •≥55 years: WHtR RR 1.38
• •Predictive value maintained into older age

By Geographic Region:

• •European studies: WHtR RR 1.42
• •Asian studies: WHtR RR 1.47
• •North American: WHtR RR 1.39
• •Globally consistent findings

By Follow-up Duration:

• •3-5 years: WHtR RR 1.44
• •5-10 years: WHtR RR 1.40
• •

  10 years: WHtR RR 1.36

• •Long-term predictive validity confirmed

Dose-Response Relationship

CVD Risk by WHtR Level:

WHtR Category	Relative Risk
<0.45	Reference (1.0)
0.45-0.50	1.14
0.50-0.55	1.38
0.55-0.60	1.62
>0.60	2.05

Clear gradient supporting WHtR as continuous predictor with actionable thresholds.

Mechanistic Discussion

Why Central Adiposity Predicts CVD:

1. •

   Visceral Fat and Atherogenesis:

   • •Portal delivery of FFA to liver
   • •VLDL overproduction → dyslipidemia
   • •Hepatic insulin resistance → glucose intolerance
2. •

   Inflammatory Pathway:

   • •Visceral adipocytes secrete IL-6, TNF-α
   • •CRP elevation from hepatic stimulation
   • •Systemic inflammation drives atherosclerosis
3. •

   Adipokine Dysregulation:

   • •Decreased adiponectin (anti-atherogenic)
   • •Increased resistin, leptin resistance
   • •Impaired vascular function
4. •

   Direct Cardiac Effects:

   • •Epicardial fat accumulation
   • •Cardiac lipotoxicity
   • •Arrhythmia substrate

Clinical Implications

Guideline Recommendations Supported: This meta-analysis supported inclusion of waist measurement in:

• •ATP III metabolic syndrome criteria
• •IDF cardiovascular risk assessment
• •WHO obesity classification

Practical Application:

1. •Measure WHtR in all cardiovascular risk assessments
2. •WHtR >0.5 triggers intervention regardless of BMI
3. •Risk reduction targets should include WHtR reduction
4. •Monitor WHtR alongside traditional risk factors

Study Strengths

1. •Large pooled sample: >310,000 participants
2. •Hard CVD endpoints: Not just risk factors
3. •Long follow-up: Up to 20 years in some studies
4. •Geographic diversity: Global applicability
5. •Direct comparisons: WHtR vs. BMI vs. WC in same analyses

Metabolic Health Perspective

The Lee meta-analysis provides compelling evidence for WHtR in metabolic health:

Cardiovascular Risk Focus:

• •CVD is the leading cause of death globally
• •Central adiposity is a modifiable risk factor
• •WHtR identifies those at elevated CVD risk
• •Risk is continuous — every 0.05 matters

For Metabolic Optimization:

1. •WHtR reduction = CVD risk reduction
2. •Target WHtR <0.5 for primary prevention
3. •Track WHtR alongside lipids and blood pressure
4. •Lifestyle changes that lower WHtR improve CV outcomes

The Big Picture: This meta-analysis confirms that where you carry fat matters more than how much you weigh. WHtR captures this central adiposity signal and predicts the cardiovascular consequences. For anyone pursuing metabolic health, WHtR is an essential metric for tracking progress and estimating cardiovascular benefit.