Exploring Avenues for Raising HDL Cholesterol

Studies have shown that phosphatidylinositol (PI) can stimulate reverse cholesterol transport by enhancing the flux of cholesterol into HDL and by promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the liver and bile. The goal of this study was to determine the safety and therapeutic value of PI after oral administration to normolipidemic human subjects. We performed a randomized 2 week study in 16 normolipidemic subjects. Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well tolerated by all subjects. PI significantly affected the levels of HDL-C and triglyceride in the plasma of subjects receiving PI with food. The lower dose showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18% over the 2 week period. Both low- and high-dose groups showed significant increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma triglycerides by 36% in the fed subjects. These data suggest that after only 2 weeks, PI may have a comparable therapeutic value to niacin, with negligible side effects.

BackgroundLow plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia’s Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors associated with low HDL-C.MethodsPubMed, Medline and Informit ATSI Health databases were systematically searched between 1950 and 2012 for studies on Indigenous Australians reporting mean HDL-C levels in both sexes. Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as: <1.0 mmol/L. Analyses of primary data associating measures of HDL-C with other CVD risk factors were also performed.ResultsFifteen of 93 retrieved studies were identified for inclusion. These provided 58 mean HDL-C levels; 29 for each sex, most obtained in rural/regional (20%) or remote settings (60%) and including 51–1641 participants. For Australian Aborigines, mean HDL-C values ranged between 0.81-1.50 mmol/L in females and 0.76-1.60 mmol/L in males. Two of 15 studies reported HDL-C levels for Torres Strait Islander populations, mean HDL-C: 1.00 or 1.11 mmol/L for females and 1.01 or 1.13 mmol/L for males. Low HDL-C was observed only in rural/regional and remote settings - not in national or urban studies (n = 3) in either gender. Diabetes prevalence, mean/median waist-to-hip ratio and circulating C-reactive protein levels were negatively associated with HDL-C levels (all P < 0.05). Thirty-four per cent of studies reported lower mean HDL-C levels in females than in males.ConclusionsVery low mean HDL-C levels are common in Australian Indigenous populations living in rural and remote communities. Inverse associations between HDL-C and central obesity, diabetes prevalence and inflammatory markers suggest a particularly adverse CVD risk factor profile. An absence of sex dichotomy in HDL-C levels warrants further investigation.

An Evidence-Based Review of Exercise and Metabolic Syndrome

Effects of lecithin: Cholesterol acyltransferase genotypes, enzyme levels, and activity on high-density lipoprotein levels

Increased Prevalence of low High-density Lipoprotein Cholesterol (HDL-C) Levels in Korean Adults: Analysis of the Three Korean National Health and Nutrition Examination Surveys (KNHANES 1998–2005)

A low serum high density lipoprotein cholesterol (HDL-C) level is a potent predictor of coronary heart disease (CHD). It has been estimated that 11% of the Framingham men have isolated low HDL-C levels and about 30% of dyslipidemia patients have HDL-C level of less than 35 mg/dl (hypoalphalipoproteinemia). In addition, there is uncertainty regarding the management of these patients. There is no epidemiological data on the prevalence low HDL-C level in dyslipidemia patients and the results of treatment on HDL-C on a large number of patients in Indonesia. We conducted a survey in 13 cities in Indonesia to evaluate the prevalence of hypoalphalipoproteinemia among dyslipidemic patients and the impact of treatment with lipid modification drugs on achieving target level of HDL-C 35 mg/dl or more in routine clinical practice. A total number of 1420 dyslipidemia patients (mean age 50 years, male 58%) were included and analyzed in this report. The overall prevalence of hypoalphalipoproteinemia in our study was 35.4% and it was correlated with the risk level of the patients; 21.9% among low risk group (patient with &lt; 2 other risk factor), 39.6% in high risk group (≥ 2 other risk factors) and 44.3% in patients with CHD. After 12 week treatment, the prevalence decreased to 12%, 20% and 18% in low risk, high risk and CHD patients respectively. The magnitude of HDL-C changes correlated inversely with base-line HDL-C and it was highest (59%) in the lowest HDL-C group (&lt; 25 mg/dl) and the least change (23%) was found in group with the highest HDL-C level (≥ 45 mg/dl). Only 46% of patients with low HDL-C value at baseline achieved normal HDL-C level after treatment. In conclusion, the prevalence of low HDL-C in dyslipidemia patients was high especially in high risk group and in CHD patients. The majority of patients with low HDL-C at base-line could not reach the target level for HDL-C of 35 mg/dl or more after 12 weeks treatment with lipid modification drugs. (Med J Indones 2001; 10: 98-102)Keywords: hypoalphalipoproteinemia, dyslipidemia, routine practice, anti lipid drugs

Background&amp;Aims: A certain lipoprotein, especially lower low-density lipoprotein cholesterol (LDL-C), has been said to be a risk of developing intracerebral hemorrhage (ICH). However, the correlation between lipoprotein levels and hematoma expansion (HE) following ICH remains unknown. We aimed to elucidate the relation between LDL-C and high-density lipoprotein cholesterol (HDL-C) levels and HE following acute ICH. Methods: Consecutive patients with acute ICH admitted between July 2012 and November 2023 were retrospectively screened using Kagoshima Medical Center Stroke Database. The inclusion criteria were as follows: 1) onset to door time within 7 days; 2) availability of serum LDL-C and HDL-C levels evaluation on admission; and 3) availability of HE evaluation, defined as an increase of 12.5 mL and a 33% relative increase in hematoma volume on CT performed more than 24 hours after admission compared to baseline. We investigated the association between LDL-C and HDL-C levels and HE by performing Poisson regression analyses with a robust variance estimator adjusted by the following prespecified risk factors for HE: sex, age, use of antiplatelet drugs and anticoagulants before admission, body mass index, and systolic blood pressure on admission. Further, as a sensitivity analysis, we performed the same analysis above by limiting the patients with onset to door time within 24 hours. Results: We screened 608 consecutive ICH patients. Of them, 538 were identified (279 [52%] males, median age 76 years). HE was observed in 51 patients (9%). In multivariable analysis, lower HDL-C was independently associated with HE (prevalence ration (PR) 0.819, 95% CI 0.677-0.990, p = 0.039, Figure 1A). Further, a negative linear trend was observed between HDL-C quartiles and HE in reference to HDL-C Quartile 4 (Q1: PR 2.910, Q2: PR 1.860, Q3: PR 1.251, Q4: PR 1.000, p = 0.008 for trend, Figure 1B). On the other hand, LDL-C was not associated with HE (PR 1.011, 95% CI 0.935-1.094, p = 0.777). In a sensitivity analysis, lower HDL-C was also independently associated with HE (PR 0.752, 95% CI 0.591-0.956, p = 0.020, Figure 2A) with a negative linear trend (Q1: PR 3.784, Q2: PR 1.658, Q3: PR 1.161, Q4: PR 1.000, p = 0.001 for trend, Figure 2B). LDL-C was not similarly associated with HE (PR 1.030, 95% CI 0.946-1.122, p = 0.493). Conclusions: In acute ICH patients, lower HDL-C was associated with HE. HDL-C might have a protective role for HE following ICH.

Obesity and Atherogenic Dyslipidemia

BackgroundEpidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies.ObjectiveTo examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels.Methods and ResultsFifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport.ConclusionSubjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels.

Low plasma high density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary heart disease (CHD) in adults. In the field of pediatrics, subjects with low plasma HDL-C are often found among obese or dyslipidemic children. However, it is not clear whether low HDL-C in children should be considered a risk factor for CHD. The purpose of this study was to evaluate the risk for CHD in children with low HDL-C by comparing their lipid and apolipoprotein levels and physicochemical characteristics of their HDL with those of age-matched children with normal HDL-C and CHD patients with low HDL-C. Plasma lipids and apolipoproteins were measured in 206 dyslipidemic children (dyslipidemic), 65 obese children (obese), 93 CHD patients with low HDL-C (<40 mg/dl) and 128 children with normal HDL-C (controls). To evaluate the physicochemical characteristics of HDL, molar and fractional esterification rates of cholesterol in plasma (MER plasma and FER plasma) and HDL (MER HDL and FER HDL) were determined in 128 children with normal HDL-C, 71 dyslipidemic, 33 obese and 93 CHD who allowed second blood samples to be taken. Compared to controls, children with low HDL-C showed atherogenic profiles of lipid and apolipoprotein levels and physicochemical characteristics of HDL (lower apo A-I, lower ratio of apo A-I to apo B and higher FER HDL). Therefore, the differences in lipid and apolipoprotein profiles between children with low HDL-C and CHD patients with low HDL-C were examined next. The two groups of subjects based on the HDL-C level (Group I: <30 mg/dl, Group II 30 < HDL-C<40 mg/dl) were studied. Compared to CHD, Group I children showed less atherogenic apolipoprotein profiles (lower apo B and higher ratio of apo A-I to apo B). Similar findings were also found in Group II children, but the differences were less prominent than those in Group I children. FER HDL in children with low HDL-C were similar to those in CHD. These findings suggest that the physicochemical characteristics of HDL in children with low HDL-C are similar to those in CHD, but the abnormalities of apo B-containing lipoproteins are milder than those in CHD patients. Thus, if further changes in the nature of apo B-containing lipoproteins could be prevented, children with low HDL-C might not become high risk for CHD in later life.

The impact of high-density lipoprotein cholesterol levels on long-term outcomes after non–ST-elevation myocardial infarction

Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis

Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels

Lipoprotein levels in elderly patients with asthma

Low high-density lipoprotein cholesterol (HDL-C) levels are an independent predictor of ischemic events in patients with atherosclerotic cardiovascular disease. This may in part be due to decreased clopidogrel-mediated platelet inhibition in patients with low HDL-C. We investigated the association of HDL-C with on-treatment platelet reactivity to adenosine diphosphate (ADP) in 314 patients on dual antiplatelet therapy with clopidogrel and aspirin undergoing angioplasty and stenting. Platelet P-selectin expression was assessed by flow cytometry, and platelet aggregation was determined by the VerifyNow P2Y12 assay and the Impact-R. High-density lipoprotein cholesterol levels were inversely associated with P-selectin expression and the VerifyNow P2Y12 assay (both P ≤ .01). Moreover, we found a positive correlation of HDL-C with surface coverage by the Impact-R ( P = .003). Patients with low HDL-C (≤35 mg/dL) exhibited a significantly higher P-selectin expression in response to ADP and higher platelet aggregation by the VerifyNow P2Y12 assay and the Impact-R than patients with normal HDL-C (>35 mg/dL; all P < .05). High on-treatment residual platelet reactivity by the VerifyNow P2Y12 assay occurred significantly more frequently in patients with low HDL-C levels than in those with normal HDL-C (47.4% vs 30.1%, P = .01). In conclusion, low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting.