Lipid transfer to HDL and HDL-c levels impaired in long-term bedridden patients
Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers
Sedentary subjects are likely to develop a pro-atherogenic plasma lipid profile, with elevated triglycerides and diminished HDL-c levels as compared with subjects who regularly do exercise [1-3]. Whether LDL-c is higher in sedentary subjects, is debated, although CV events are clearly more common in sedentary individuals than in physically active persons . Exercise training is known to decrease serum triglycerides and promotes an increase of HDL-c .
HDL is important in reverse cholesterol transport, in which cholesterol is transferred from the cells to HDL for subsequent excretion by the liver. In addition to this endogenous anti-atherogenic effect, HDL also has antioxidant, anti-inflammatory, anti-thrombotic, anti-apoptotic and vasodilatory effects [5,6]. In certain disease states, these beneficial functions of HDL can be affected, and even impair the lipoprotein such that it can become pro-inflammatory or pro-atherogenic [7-9]. Thus, evaluation of HDL functional aspects may be important for the understanding of the impact of HDL on atherogenesis.
The researchers of the current article developed a practical in vitro assay of the transfers of unesterified cholesterol, cholesterol esters, triglycerides and phospholipids to HDL, mediated by cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) . This study evaluated whether the intravascular lipid metabolism could be further worsened in bedridden patients, in which physical activity is reduced to a minimum, compared with sedentary subjects. 23 bedridden, clinically stable patients under long-term (>90 days) care, were selected (bedridden period ranged from 3 months to 6 years). These patients were compared with 26 normolipidemic sedentary volunteers, paired for age and gender. Blood samples were taken after 12 hours fasting.
- Mean BMI was lower in the bedridden than in the sedentary group (21.9 ± 3.0 vs. 25.4 ± 2.7, P<0.001).
- Bedridden patients showed lower levels than sedentary subjects of total cholesterol (160 ± 43 vs. 193 ± 36 mg/dL, P=0.005), non-HDL-c (125 ± 40 vs. 148 ± 36 mg/dL, P=0.034), LDL-c (96 ± 33 vs. 1124 ± 31 mg/dL, P=0.003), HDL-c (36 ± 13 vs 45 ± 10 mg/dL, P=0.008), oxidized LDL (43 ± 12 vs. 53 ± 13 mg/dL, P=0.011) and Apo A-1 (111 ± 24 vs. 134 ± 20 mg/dL, P=0.001).
No differences were seen in levels of apoB, CETP and LCAT, as well as glucose, insulin and leptin.
- Transfer of all four lipids from the lipid nanoparticles to the HDL fraction was lower in bedridden patients compared to sedentary subjects (cholesteryl esters: 4.8 ± 1.27 vs. 6.24 ± 1.10%, P=0.0001, unesterified cholesterol: 3.05 ±1.10 ± 4.04 ± 1.07, P=0.0022, phospholipids: 17.32 ± 2.02 vs. 19.06 ± 1.31, P=0.0007, triglycerides: 3.06 ± 0.65 vs. 3.65 ± 0.71, P=0.0037).
- When these date were normalized by either HDL-c or apo A-I plasma levels, the transfer of cholesterol esters, unesterified cholesterol and triglycerides was no longer significantly different between the two groups. Phospholipid transfer corrected by HDL-c was higher in bedridden patients than in sedentary subjects (0.537 ± 0.157 vs. 0.444 ± 0.093, P=0.0134), as well as when corrected by Apo A-I (0.161 ± 0.026 vs. 0.145 ± 0.019, P=0.0166).
- Serum concentrations of inflammatory markers IL-1β, IL-6, IL-8, HGF and NGF were significantly higher in bedridden patients, while no differences were seen between groups in levels of MCP-1 and TNF-α.
This study showed that the transfer of all four lipids to HDL was impaired in bedridden patients, as compared with sedentary subjects. This may be related to their lower HDL-c levels, as suggested by disappearance of the effect upon normalization by HDL-c levels or Apo A-I. Thus, the diminished lipid transfer does not seem to be the consequence of impaired ability of HDL particles to receive cholesterol. The data suggest that even low levels of physical activity exerted in the day-to-day life of sedentary subjects support HDL concentration and lipid transfer rates, as compared with complete inactivity.
The unexpected finding that LDL-c was lower in bedridden patients, may be explained by the standard infirmary diet that the patients received, with presumably lower calorie and fat intake compared with the free-living control sedentary subjects.