A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD), which may be exacerbated by the major AD genetic risk factor apolipoprotein Eε4 (APOEε4). Since subjective memory complaint (SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. As amyloid-ε (Aβ) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reduced HDL, and increased body fat) would be associated with plasma Aβ levels. We explored this in 198 individuals with and without SMC (average age = 63 years). Correlations between Aβ40 and HDL were observed, which were stronger in non-APOEε4 carriers (rho = -0.315, p < 0.001) and in SMC (rho = -0.322, p = 0.01). There was no relationship between percentage body fat and Aβ40 in this cohort. Age and HDL remained predictive for plasma Aβ40 using multivariate regression analysis. We report a novel negative association between HDL and Aβ, which if demonstrated to be causal has implications for the development of lifestyle interventions and/or novel therapeutics. The relationship between HDL and Aβ and the potential significance of such an association needs to be validated in a larger longitudinal study.