Dyslipidemia in American Indian Adolescents and Young Adults: Strong Heart Family Study

Abstract

Background: Although many studies on the association between dyslipidemia and cardiovascular disease (CVD) exist in older adults, data on the association among adolescents and young adults living with disproportionate burden of cardiometabolic disorders are scarce.

Methods and results: The SHFS (Strong Heart Family Study) is a multicenter, family-based, prospective cohort study of CVD in an American Indian populations, including 12 communities in central Arizona, southwestern Oklahoma, and the Dakotas. We evaluated SHFS participants, who were 15 to 39 years old at the baseline examination in 2001 to 2003 (n=1440). Lipids were measured after a 12-hour fast. We used carotid ultrasounds to detect plaque at baseline and follow-up in 2006 to 2009 (median follow-up=5.5 years). We identified incident CVD events through 2020 with a median follow-up of 18.5 years. We used shared frailty proportional hazards models to assess the association between dyslipidemia and subclinical or clinical CVD, while controlling for covariates. Baseline dyslipidemia prevalence was 55.2%, 73.6%, and 78.0% for participants 15 to 19, 20 to 29, and 30 to 39 years old, respectively. Approximately 2.8% had low-density lipoprotein cholesterol ≥160 mg/dL, which is higher than the recommended threshold for lifestyle or medical interventions in young adults of 20 to 39 years old. During follow-up, 9.9% had incident plaque (109/1104 plaque-free participants with baseline and follow-up ultrasounds), 11.0% had plaque progression (128/1165 with both baseline and follow-up ultrasounds), and 9% had incident CVD (127/1416 CVD-free participants at baseline). Plaque incidence and progression were higher in participants with total cholesterol ≥200 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, or non-high-density lipoprotein cholesterol ≥130 mg/dL, while controlling for covariates. CVD risk was independently associated with low-density lipoprotein cholesterol ≥160 mg/dL.

Conclusions: Dyslipidemia is a modifiable risk factor that is associated with both subclinical and clinical CVD, even among the younger American Indian population who have unexpectedly high rates of significant CVD events. Therefore, this population is likely to benefit from a variety of evidence-based interventions including screening, educational, lifestyle, and guideline-directed medical therapy at an early age.

Keywords: American Indian; Strong Heart Family Study; adolescent; atherosclerosis; cardiovascular disease; dyslipidemia; young adult.

Figure 1. Sample sizes and length of follow‐up for the Strong Heart Family study baseline assessments of American Indian adolescents and young adults ages 15 to <40.

Of the 1440 American Indian participants who met the age requirements, 12 has missing lipid assessments. We excluded these participants from the cross‐sectional dyslipidemia prevalence analysis, leaving 1428. Of the 1428 with lipid assessment, 12 had cardiovascular disease (CVD) at baseline according to chart review. We excluded these participants from the incident CVD analysis, because they had prevalent CVD, leaving 1416 with yearly CVD surveillance. Of the participants who were CVD‐free at baseline, 1165 had ultrasounds at both baseline and follow‐up. There were 13 participants with missing ultrasounds at baseline, 241 were missing at follow‐up, and 3 were missing both baseline and follow‐up ultrasounds, leaving 251 who were missing ultrasound measurements at baseline or follow‐up. Of the 170 who had plaque at follow‐up, 61 had plaque at baseline, leaving 109 with incident plaque. *This is the age range of surviving participants as of December 31, 2020. At the end of surveillance follow‐up, 121 (8.5%) deaths had occurred. Of these 121 deaths, 30 (25%) were CVD‐related.

Figure 2. Univariate analysis of plaque incidence, plaque progression, and cardiovascular disease incidence (per 1000 person‐years) according to baseline demographic and cardiovascular disease risk factors in American Indian adolescents and young adults, ages 15 to <40 years, during a median of 5 years of follow‐up for plaque outcomes and 19 years for CVD outcomes.

Age is divided at median of the study population (26.8 years). Increased WC is defined as >100 cm for men and >90 cm for women. Hypertension is ≥140/90 mm Hg. Diabetes is fasting plasma glucose level ≥126 mg/dL or the use antidiabetes medication. Albuminuria is an albumin‐creatinine ratio ≥30 mg/g. Metabolic syndrome is the presence of at least 3 of 5 components: increased WC, high triglycerides, low HDL‐C, hypertension, or high fasting glucose (>100 mg/dL). Total cholesterol is ≥200 mg/dL, LDL‐C is ≥100 mg/dL, very high LDL‐C is ≥160 mg/dL, HDL‐C is <40 mg/dL for men or <50 mg/dL for women, non–HDL‐C is ≥130 mg/dL, and triglycerides is ≥150 mg/dL. Dyslipidemia is the presence of any abnormal levels of total cholesterol, LDL‐C, HDL‐C, non–HDL‐C, triglycerides, or taking lipid‐lowering medication. *P<0.0001, ^† P<0.01, ^‡ P<0.05; comparisons without these symbols were not statistically significant. P values are from log‐rank tests. CVD indicates cardiovascular disease; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; Met‐S, metabolic syndrome; and WC, waist circumference.

Figure 3. Plaque‐free, plaque progression, and cardiovascular disease‐free probability for American Indian adolescents and young adults, ages 15 to <40, with versus without dyslipidemia at baseline.

Dyslipidemia is defined as any abnormal levels of total cholesterol (≥200 mg/dL), low‐density lipoprotein cholesterol (≥100 mg/dL), high‐density lipoprotein cholesterol (>40 mg/dL for men or <50 mg/dL for women), non–high‐density lipoprotein cholesterol (≤130 mg/dL), triglycerides (≤150 mg/dL), or taking lipid‐lowering medication. Blue and red lines represent the times to plaque development, plaque progression, or cardiovascular disease for participants with or without baseline dyslipidemia, respectively. The plus symbols (+) represent censored participants.