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Cerebrovascular resistance is a pressure-dependent mechanism resulting from cerebral autoregulation, which is the normal buffering of changes in arterial blood pressure. Lifestyle habits are known to have an influence; however, its magnitude is still unclear. The aim of this study was to assess the contribution of additive genetic, shared and unshared environmental factors to changes in middle cerebral artery (MCA) mean flow velocities (MFVs) and pulsatility index.One hundred and forty-three Italian twin pairs from Padua, Perugia and Rome (68 monozygotic, 75 dizygotic, 55 ± 12 years) underwent transcranial Doppler sonography of the MCA bilaterally. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of averaged MFV and pulsatility index into additive genetic, shared and unique environmental effects adjusted by age and sex.MFV was heritable in 30.6% [95% confidence interval (CI) 0.8–67.3%], and shared and unshared environmental factors explained 47.7 and 21.6% of the variance (95% CI 14.4–71.9% and 12.6–32.0%). Pulsatility index was not genetically determined, but unique and common environmental factors were responsible for 54.2 and 38.1% of the variance (95% CI 36.3–71.8% and 0.0–57.8%).These findings underline the importance of identification of the specific genes and common environmental factors related to MFV. Individuals with positive family history of stroke related to the atherosclerosis of MCA might take advantage from preventive ultrasound screening. More emphasis should be placed on the prevention of the known related common environmental factors on MFV and the individual lifestyle risk factors on pulsatility index.