Individual-ecological triangulation of risk factors for peripheral artery disease: concordant evidence for smoking and diabetes, discordant evidence for kidney disease

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Background: Peripheral artery disease (PAD) is studied either through individual-level cohorts or national mortality statistics; the two evidence streams carry different biases and have not been formally compared within one design. Methods: We triangulated two pre-specified streams. Individually, we analyzed 3,268 NHANES 1999-2004 participants aged 40 years and older with ankle-brachial index measurements (235 with PAD) linked to mortality through 2019, using survey-weighted logistic and Cox models, a Fine-Gray model, and attributable fractions. Ecologically, we used national Multiple Cause of Death records for 1999-2024 (390,174 PAD deaths) to estimate five-year-band trends in the share of PAD deaths mentioning tobacco (F17.0-F17.9), diabetes (E00-E89), or renal failure (N17-N19). Per a pre-specified protocol, we compared directions of association, each bridge quantified by a bootstrap direction-agreement probability. Results: Weighted PAD prevalence was 5.05% (95% CI, 4.18 to 5.92). PAD was associated with cardiovascular death (hazard ratio, 2.65; 95% CI, 1.87 to 3.76). Smoking showed the strongest PAD association (odds ratio, 3.37) and the steepest rise in its mortality share (2.20% to 18.50%; direction-agreement probability, 1.000). Diabetes was associated with PAD (1.68) and rose after a 2014 trough (7.35% to 10.92%; probability, 1.000). Renal failure was associated with PAD (1.78) but its mortality share was flat for 26 years (14.55% to 14.49%; probability, 0.445). Conclusions: The two streams agreed in direction for smoking and diabetes and diverged for kidney disease, reflecting different estimands. Smoking and diabetes are the factors supported by both streams for population-level PAD prevention.