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Objectives: To determine the population distribution of cardiovascular risk in eight low- and middle-income countries and compare the cost of drug treatment based on cardiovascular risk (cardiovascular risk thresholds ≥ 30%/≥ 40%) with single risk factor cutoff levels., Study Design and Setting: Using World Health Organization (WHO) and the International Society of Hypertension risk prediction charts, cardiovascular risk was categorized in a cross-sectional study of 8,625 randomly selected people aged 40-80 years (mean age, 54.6 years) from defined geographic regions of Nigeria, Iran, China, Pakistan, Georgia, Nepal, Cuba, and Sri Lanka. Cost estimates for drug therapy were calculated for three countries., Results: A large fraction (90.0-98.9%) of the study population has a 10-year cardiovascular risk <20%. Only 0.2-4.8% are in the high-risk categories (≥ 30%). Adopting a total risk approach and WHO guidelines recommendations would restrict unnecessary drug treatment and reduce the drug costs significantly., Conclusion: Adopting a total cardiovascular risk approach instead of a single risk factor approach reduces health care expenditure by reducing drug costs. Therefore, limited resources can be more efficiently used to target high-risk people who will benefit the most. This strategy needs to be complemented with population-wide measures to shift the cardiovascular risk distribution of the whole population., (Copyright © 2011 Elsevier Inc. All rights reserved.)