Lipid parameters strongly depend on age and sex
Lipid and lipoprotein reference values from 133,450 Dutch Lifelines participants: Age- and gender-specific baseline lipid values and percentilesLiterature - Balder JW, de Vries JK, Nolte IM, et al., - J Clin Lipidol. 2017; 11 (4): 1055–1064.e6
Considering that plaque formation already starts at a very young age, early prevention is the preferred approach to curb the LDL-c related progression and associated chronic disease. Thus, identification of modifiable risk factors, especially dyslipidemia, is key to effective prevention and management of CVD.
The Lifelines cohort study was initiated in 2006 and is the largest ongoing prospective observational European population study to date . 152180 adult inhabitants of the northern part of The Netherlands have been recruited through their primary care physician, through family or by registering at lifelines.nl. The 5-year follow-up visit is in process, and the 10-year follow-up visit is being planned. Total duration of follow-up will be 30 years. By means of self-reported/validated questionnaires (every 1,5 years), routine clinical biochemistry, physical examination, biobanking of blood, urine and feces and genome-wide genotyping, Lifelines can provide insight into the prevalence and incidence of multifactorial disease and their risk factors.
Knowing the normal distribution of blood lipids in the population is necessary to identify dyslipidemia. Although reference values for total cholesterol (TC), LDL-c, HDL-c and triglycerides (TG) have been collected in various cohorts, contemporary and comprehensive percentile-based reference values are lacking. These values may vary with geographical region , and are time-dependent, considering changes in age, lifestyle and pharmaceutical interventions [3,4].
This article aims to provide age- and gender-based reference values for lipid levels, to be able to compare levels with populations in a given region or a specific genetic background, and it can facilitate future research, to monitor prospective changes. For this analysis, participants were included between 2006 and 2013, almost exclusively of Caucasian descent. No data of children <18 years old were included in this analysis, and those with a history of CVD (myocardial infarction, coronary surgery or stroke) or those using lipid-lowering drugs at baseline were excluded.
- Women (n=79475, 60%) presented with an overall more favorable CV risk profile than men (54065, 40%), as seen by significantly lower mean systolic blood pressure (122 vs. 130 mmHg), lower median TC (193 vs. 197 mg/dL), lower median LDL-c (116 vs. 131 mg/dL), higher median HDL-c (62 vs. 50 mg/dL), lower TG (77 vs. 100 mg) and lower smoking rates (19.7% vs. 23.3%).
- At 20 years of age, men had significantly lower LDL-C levels than women (median: 85 vs. 97 mg/dL, 95th percentile: 139 vs. 151 mg/dL, P<0.001).
- In both genders, LDL-c (direct quantification) increases with age, but the pattern differs. In men LDL-c peaked at 45-49 years of age (median: 139 mg/dL, 95th percentile: 197 mg/dL). At higher ages, LDL-c showed a gradual decrease. In women, median LDL-c was stable until their mid-30s, after which a maximum level (median: 143 mg/dL, 95th percentile: 205 mg/dL) was seen at 55-59 years of age. Women showed no clear decline at higher ages.
- Friedewald-calculated LDL-c levels yielded lower values than direct LDL-c quantification, in both genders (median 7.0 mg/dL lower in men and 6.0 mg/dL lower in women).
- HDL-c did not significantly change with increasing age in men, while in women, median HDL-c increased from 54 mg/dL at young age (<20) to 66 mg/dL at the age of 50 years old. In women older than 50 years, no changes in HDL-c were noted.
- Of all lipids, the relation between TG and age differed most between men and women. Men showed a clear increase from young age (median: 71 mg/dL, 95th percentile: 153 mg/dL) to 40-44 years (median: 106 mg/dL, 95th percentile: 289 mg/dL), after which TG levels dropped rapidly with increasing age. This decline was most prominent at the higher end of the spectrum (75th, 90th and 95th percentiles), and almost absent at the 5th and 10th percentile. TG levels were relatively stable in women, and median levels fluctuated between 68 and 77 mg/dL between the ages of 20 and 50 years. TG levels increased moderately in women >50 years old.
- Reference values of all blood lipids for men and women at five years-intervals have been made available at my-cholesterol.care.
These data of the three-generation Lifelines cohort show prominent gender- and age-related differences in all main plasma lipids and lipoproteins, suggesting the need to correct for age and sex when evaluating a person’s lipid profile.
The prevalence of high LDL-c in young individuals was higher in this region of the Netherlands than anticipated. The presented data and the accompanying website can facilitate evaluation of (population) interventions or be used as a comparator for other prospective or retrospective lipid profile analyses in other geographic regions. The interactive website may serve as a tool to identify young individuals with atherogenic dyslipidemia.