Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian Population.

Background: The contribution of high-density lipoprotein cholesterol (HDL-C) subclasses to incident cardiovascular disease (CVD) and coronary heart disease (CHD) remains a subject of debate. Objectives: The objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and CVD. Methods: In a nested case-control study, HDL-C and its subclasses (HDL2-C and HDL3-C) in 370 age and gender-matched case and control subjects were determined. This study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ORs) for the associations between HDL-C, HDL2-C, HDL3-C, and HDL2-C/HDL3-C (both as continuous and categorical variables) with incident CVD and CHD. The present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature CVD, non-HDL-C, and triglycerides. Results: In multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in HDL-C and HDL3-C was associated with a reduced risk of incident CVD and CHD. For CVD, the ORs (95% confidence intervals [CI]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for HDL-C and HDL3-C, respectively. The corresponding values for CHD were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). In the categorical approach to lipoprotein parameters, higher quartiles of HDL-C and HDL3-C, compared to the first quartile, were significantly associated with a lower risk of incident CVD and CHD. The ORs (95% CI) for the fourth quartiles were 0.43 (0.25 - 0.74, P for trend = 0.003) and 0.46 (0.27 - 0.78, P for trend = 0.005) for HDL-C and HDL3-C regarding CVD and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all P for trend = 0.001) regarding CHD, respectively. Paradoxically, across quartiles of HDL2-C/HDL3-C, this lipid ratio was associated with a higher risk of CHD (92% higher risk in the fourth quartile). Conclusions: The results showed that HDL3-C, but not HDL2-C, was primarily responsible for the protective effect of HDL-C against CVD, particularly CHD, in Iranian adults.

Association of LDL-cholesterol subfractions with cardiovascular disorders: a systematic review.

BACKGROUND: Cardiovascular disorders (CVDs) are the leading cause of death worldwide. This study aimed to evaluate the association between low-density lipoprotein (LDL) subfractions and cardiovascular disorders. METHODS: To ensure the rigor of the systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. For this systematic review, a comprehensive search strategy was performed in important databases including PubMed, Scopus, Embase, International Statistical Institute (ISI) Web of Science, and google scholar from 2009 to February 2021. The following terms were used for systematic search: low-density lipoprotein, LDL, subfractions, subclasses, nuclear magnetic resonance, NMR, chromatography, high-pressure liquid, HPLC, cardiovascular disease, cerebrovascular, and peripheral vascular disease. Also, for evaluating the risk of bias, the Newcastle-Ottawa scale was employed. RESULTS: At the end of the search process, 33 articles were included in this study. The results of most of the evaluated studies revealed that a higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Also, small dense LDL was associated with an increased risk of CVDs. There was no association between LDL subfraction and CVDs in a small number of studies. CONCLUSIONS: Overall, it seems that the evaluation of LDL subclasses can be used as a very suitable biomarker for the assessment and diagnosis of cardiovascular diseases. However, further studies are required to identify the mechanisms involved.

Association of triglycerides to high-density lipoprotein cholesterol ratio to identify future prediabetes and type 2 diabetes mellitus: over one-decade follow-up in the Iranian population.

BACKGROUND: To determine the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for identifying subjects at risk of incident prediabetes and type 2 diabetes mellitus (T2DM). METHODS: In 5064 subjects (men = 2247) aged ≥ 20 years, using Cox proportional hazards regression analyses, the associations of TG/HDL-C with incident prediabetes and T2DM were examined among normoglycemic men and women. Furthermore, the association of this lipid ratio with incident T2DM was also assessed among prediabetic subjects (n = 1414). The multivariable analyses were adjusted for age, body mass index, waist-to-height ratio, wrist circumference, systolic blood pressure, family history of T2DM, education level, history of cardiovascular diseases, and fasting plasma glucose (FPG). RESULTS: During a median follow-up of 11.2 years, 2140 new cases of prediabetes (men = 1070) and 360 incident T2DM (men = 152) were identified among normoglycemic individuals. In the prediabetic population, 574 new cases of T2DM (men = 252) were developed. Among the whole population, compared to the first quartile (reference), higher quartiles of TG/HDL-C were significantly associated with higher risks of incident prediabetes and T2DM among normoglycemic individuals and incident T2DM in the prediabetic population (all P for trend < 0.001). The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for the fourth quartiles were 1.37(1.20-1.58), 1.92(1.34-2.75), and 1.57(1.22-2.01), respectively. The sex-stratified analyses demonstrated similar significant associations in both sexes; however, TG/HDL-C lost its association with incident T2DM among prediabetic men. Among the normoglycemic population, 1 unit increase in TG/HDL-C was significantly associated with incident prediabetes and T2DM [1.02(1.00-1.03) and 1.06(1.03-1.08), respectively]. The corresponding value for incident T2DM in prediabetic individuals was 1.01(1.00-1.03). In a subgroup population having insulin data (n = 2897), the associations between TG/HDL-C and incident prediabetes and T2DM among normoglycemic individuals generally persisted even after replacing FPG with an index of insulin resistance (IR), i.e., homeostasis model assessment of IR (HOMA-IR) in the adjusted model. CONCLUSIONS: In conclusion, in the normoglycemic population, the increasing value of TG/HDL-C was unfavorably associated with incident prediabetes and T2DM, especially among women. Similarly, TG/HDL-C was associated with incident T2DM in prediabetic individuals. Generally, we found that the correlation between TG/HDL-C and different states of dysglycemia is independent of HOMA-IR.

The association between low-density and non-high-density lipoprotein cholesterol with incident cardiovascular disease among low-risk Iranians during 2 decades follow-up.

INTRODUCTION: To examine the associations between low-density and non-high-density lipoprotein cholesterol (LDL-C and non-HDL-C, respectively) with incident cardiovascular disease (CVD) in low-risk subjects. MATERIALS AND METHODS: From a total of 2467 non-diabetic aged 40-70 years, free of CVD with LDL-C range 1.81 ≤ LDL-C < 4.91 mmol/L with 10-year atherosclerotic cardiovascular disease (ASCVD) risk < 7.5 %, the associations of LDL-C and non-HDL-C with incident CVD were assessed using multivariable Cox proportional hazard regression analyses adjusted for age, sex, body mass index, waist circumference, HDL-C, triglycerides, chronic kidney disease, current smoking, hypertension, and family history of CVD. RESULTS: During a median follow-up of 18 years, 559 CVD events occurred. Compared to the LDL-C < 2.59 mmol/L as reference, the categories of 2.59 ≤ LDL-C < 3.36, 3.36 ≤ LDL-C < 4.14, and ≥ 4.14 mmol/L were associated with hazard ratios (95 % confidence intervals) of 1.39(0.89-2.18), 1.72(1.11-2.68), and 2.19(1.36-3.51) for incident CVD (P for trend <0.0001), respectively. Compared to the non-HDL-C < 3.36 as reference, the categories of 3.36 ≤ non-HDL-C < 4.14, 4.14 ≤ non-HDL-C < 4.91, and ≥ 4.91 mmol/L were associated with 1.48(0.96-2.30), 1.37(0.89-2.16), and 2.15(1.36-3.39) higher risk for incident CVD (P for trend = 0.001), respectively. Among those with ASCVD score <5 % (n = 2070), even the 2.59 ≤ LDL-C < 3.36 mmol/L increased the risk for CVD [1.73(1.01-2.97)]. Results for non-HDL-C categories remained unchanged compared to those with ASCVD risk < 7.5%. CONCLUSIONS: Among Iranian individuals with ASCVD risk as little as < 5 %, LDL-C ≥ 2.59 mmol/L and non-HDL-C ≥ 3.36 mmol/L, independent of traditional risk factors, were associated with a significantly higher risk of incident CVD, individuals that might potentially benefit from pharmacological therapy.

Age- and sex-specific reference values for fasting serum insulin levels and insulin resistance/sensitivity indices in healthy Iranian adults: Tehran Lipid and Glucose Study.

OBJECTIVES: Increased insulin concentration is a surrogate for insulin resistance and early assessment of fasting insulin may help in identifying those who are potentially at high risk of type 2 diabetes, hypertension, and cardiovascular disease. The aim of this study was to determine age- and sex-related reference values for serum insulin and insulin resistance/sensitivity indices in Iranian subjects. DESIGN AND METHODS: Serum insulin levels were measured by electrochemiluminescence immunoassay in 5786 participants of the Tehran Lipid and Glucose Study. After application of exclusion criteria, 309 non-obese healthy subjects (124 men and 185 women), aged 24-83 y, were included. The International Federation of Clinical Chemistry guidelines (non-parametric method) and the robust method were used for determining reference values. RESULTS: Overall 95% reference values for fasting insulin were 1.61-11.37, 2.34-11.98, and 2.11-12.49 µU/mL in men, women, and total population respectively. Mean fasting insulin concentration showed a decreasing trend with age in both genders (p for trend ≤0.001). Age, waist circumference, and systolic blood pressures were biological determinants of fasting insulin in both genders; in addition, insulin was modulated by triglycerides in men and fasting glucose in women. Reference intervals for HOMA1-IR, HOMA2-IR, and QUICKI were 0.63-2.68, 0.40-1.80, and 0.33-0.42, respectively. CONCLUSION: This study presents the first set of reference values for fasting serum insulin to be 2-12 µU/mL for both genders in a healthy sample of Iranian adults along with the reference values for insulin resistance/sensitivity indices. These values could be used for identifying subjects with insulin resistance in epidemiological and clinical research.

Effect of pomegranate seed oil on serum TNF-α level in dyslipidemic patients.

Pomegranate punicic acid and pomegranate fruit extracts have the potential effects in inhibiting tumour necrosis factor-α (TNF-α) and inflammatory diseases. The aim of this study was to evaluate the effect of pomegranate seed oil (PSO) consumption on serum TNF-α level in dyslipidemic patients. Fifty-one subjects with serum total cholesterol concentration >200 mg/dl and serum triglyceride concentrations >150 mg/dl were randomly assigned into the PSO (n = 25) and placebo (n = 26) groups. Subjects were given 400 mg PSO or placebo capsules twice daily for 4 weeks. Six patients were excluded because of complications or lack of compliance. Serum TNF-α level was measured at baseline and after 4 weeks. Mean (SD) serum concentration of TNF-α decreased from 14.73 ± 5.25 to 13.28 ± 3.79 pg/ml in the PSO group (P = NS). Corresponding values in the placebo group were 12.46 ± 1.67 versus 13.14 ± 1.67 pg/ml (P = NS). In conclusion, administration of PSO in dyslipidemic patients does not affect the serum TNF-α.