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Little is known about isolated systolic hypertension (ISH) in younger adults. We examined the prevalence and determinants of ISH in this age group using the 1999–2004 National Health and Nutrition Examination Surveys (NHANES) and made comparisons using data from NHANES III (1988–1994).A total of 5685 adults aged 18–39 years and not on antihypertensive medications were analyzed. Prevalence estimates of ISH and potential risk factors were estimated by age and sex. For comparison of prevalence estimates with published reports of NHANES III data, age cutoffs (18–24, 25–34, and 35–44 year) by sex were also employed. A multivariate logistic regression model tested independent determinants of ISH.ISH in young adults had a higher prevalence than systolic/diastolic hypertension (1.57 ± 0.23% vs. 0.93 ± 0.18%). ISH prevalence increased within the last decade particularly for men for each respective age category [men (0.8 vs. 2.2%, 1.3 vs. 2.4%, 1.3 vs. 2.4%), women (0.0 vs. 0.3%, 0.1 vs. 0.7%, 1.7 vs. 1.8%)]. On multivariate analysis, obesity [odds ratio (OR): 2.68, 95% confidence interval (CI): 1.06, 6.77], male sex (OR: 2.19, 95% CI: 1.10, 4.37), education level less than high school (OR: 2.98, 95% CI: 1.10, 8.06), and current smoking (OR: 2.06, 95% CI: 1.03, 4.11) were characteristics independently associated with higher odds of ISH among young adults. Relative increases in prevalence between the surveys were noted for current smoking (24.3 vs. 51.5%), obesity (33.9 vs. 42.7%) and low educational level (18.4 vs. 38.6%).ISH among young adults is increasing in prevalence, and is more common than systolic/diastolic hypertension. Obesity, smoking, and low socioeconomic status appear to be important determinants of ISH among young adults and have all increased over the last decade.