In the present study, the authors selected 7,715 adults in United States from the NHANES datasets. The important discovers of this cross-sectional study were as follows: (1) PIV index had an significantly positive association with the risk of hyperlipidemia. And this effect maintained stable in both continuous and quartile independent variables even after adjustment for all confounders. The prevalence of hyperlipidemia was relatively significant in female, 20–39 years old, 25-30kg/㎡, PIR > 3.5, above high school, non-diabetic, non-hypertensive, non-smoking, and non-drinking individuals. (2) In the stratified analysis, except for BMI, age, and diabetes condition, the rest were all not statistically significant. Patients with hyperlipidemia were concentrated in young (aged 20–39 years) and overweight (BMI 25–30). Therefore, it might be necessary to call on young overweight individuals to reduce their weight reasonably to avoid the risk of hyperlipidemia in the future. Meanwhile, this new index might be a reliable predictor of dyslipidemia indirectly.
To our knowledge, the association between PIV and hyperlipidemia was first reported in this study based on a national population of the United States. The PIV was derived from the four important immune cells in plama, neutrophils, monocytes, lymphocytes, and platelets [14].
Acute inflammation was initially considered a compensatory mechanism for injury repair, but when it progressed to a chronic state, the direction of lipid synthesis altered, manifesting in a reduction of HDL and an elevation in very low-density lipoprotein (VLDL) levels [15]. The long-term existence of infection and inflammation could cause abnormal lipid metabolism [16]. In individuals with primary Sjogren’s syndrome, interleukin-2 and LDL-C were positively correlated (r = 0.7, P = 0.02) [17]. In addition, interleukin-6 (r = 0.39, P = 0.01) and tumor necrosis factor-alpha (TNF-α) levels had significant associations with TG (r = 0.4, P = 0.007) and HDL-C (r = -0.4, P < 0.001) [17]. Among individuals with heterozygous familial hypercholesterolemia, nuclear factor-kappa B (NF-kB) activity of mononuclear cells in blood was independently associated with apolipoprotein B (r = 0.287, P = 0.03) and oxidized LDL (r = 0.300, P = 0.02) [18]. Meanwhile, modified LDLs had the ability to activate the toll-like receptors, thereby priming the Nod-like receptor protein 3 inflammasomes and ultimately lead to the activation of interleukin-1β and secondary inflammatory responses [19]. In newly diagnosed patients with metabolic syndrome, there were associations between TNF-α and fasting blood glucose (r = 0.179, P = 0.021), LDL-C (r = 0.199, P = 0.01), atherogenic index (r = 0.219, P = 0.004), TG (r = 0.351, P < 0.001), and HDL-C (r = -0.244, P = 0.001) [20]. Among individuals without severe cardiovascular risks, there was a positive association between serum TG and high-sensitivity C-reactive protein (CRP) (r = 0.298, P < 0.001) [21]. In a Korean cross-sectional study, elevated CRP levels were positively associated with hypertriglyceridaemia (OR (95%CI): 1.157 (1.040–1.287); P = 0.007) [22]. In Inner Mongolia of China, individuals with the highest quartile of inflammatory biomarkers were more likely to have dyslipidemia (High-sensetivity CRP: OR (95%CI): 3.215 (2.551–4.116)) [23]. The administration of pro-atherogenic cytokines, such as TNF-α, interleukin-1β, and interleukin-6 in rats could result in an elevation of plasma VLDL-TG levels [24]. Excessive migration of LDL to the artery wall triggered an inflammatory cascade, which then accelerated the accumulation of cholesterol, further exacerbating the inflammatory response. This vicious cycle ultimately accelerated the formation of atherosclerotic plaque [25]. It was also reported that the lipoprotein-mediated enhancement of inflammation was mainly mediated by TG-rich lipoproteins, not LDL [26]. Hypertriglyceridemia enriched with apolipoproteins C-III, could activate NF-kB inflammatory signaling pathways, leading to development of atherosclerosis [27]. In mastitis mice, elevated LDL-C, TG, and TC in plasma were observed possibly due to decreased expression of lipoprotein lipase and increased expression of ANGPTL which was a liver-specific secretory protein with homology to angiopoietin [28]. In addition, the TG and cholesterol levels in plasma were elevated in mice with double-knockout genes (Tribbles homolog 1 and LDL receptor), leading to systemic inflammation and progression of atherosclerosis [29]. And the level of secretory phospholipase A2 increased during inflammation, potentially leading to an acceleration in HDL catabolism [30]. The acute-phase protein serum amyloid A1 in inflammation could remarkably alter the composition of HDL. Additionally, HDL at this stage had a decreased ability in mediating cholesterol transport and protecting LDL from oxidative stress [31].
The co-existence of inflammation and hyperlipidemia has been identified as important factors in the progression of atherosclerosis. Anti-inflammatory therapy and lipid-lowering interventions were not mutually exclusive, but had a synergistic effect [32]. Colchicine, a well-known anti-inflammatory drug, could reduce lipid levels and inflammatory markers in rats [33]. Compared with monotherapy, colchicine combined with atorvastatin further reduced inflammatory markers and lipoprotein associated phospholipase A2 in rats [34]. In individuals treated with statins, high-sensitivity CRP had a potent predictive ability of cardiovascular event (1.31 (1.20–1.43); P < 0.0001) than LDL-C [35]. In addition, women were more susceptible to hyperlipidemia in this study (1.71 (1.15–2.55) vs 1.53 (1.01–2.34); P for interaction = 0.4). Among patients aged 20 to 39 years with moderate to severe hypercholesterolemia in the United States, lipid control was worse in women than in men. It was possibly because reproductive-aged women were concerned about teratogenicity of drugs (such as statins) and underestimated the long-term cardiovascular risks [36]. Moreover, the overweight patients were more likely to have hyperlipidemia, which was similar to a cross-sectional study from the United States and Spain (The relationship between BMI and LDL had an inverted U shape) [37]. The imbalance between body weight and dyslipidemia might be related to the functional failure of adipose tissues in a state of obesity [38]. The majority of people in this study were non-diabetic, so this might explain why the proportion of non-diabetics was higher in patients with hyperlipidemia.