Hannia Campos

Low density lipoprotein particle size and coronary artery disease.

Decreased plasma low density lipoprotein (LDL) particle size has been associated with premature coronary artery disease (CAD). We examined LDL particle size by 2-16% gradient gel electrophoresis in 275 men with CAD (greater than 75% cross-sectional-area stenosis) and 822 controls. Seven major LDL size bands (with LDL-1 [d = 1.025-1.033 g/ml] being the largest and LDL-7 [d = 1.050-1.063 g/ml, the smallest]) were identified. Because most subjects had two or more adjacent LDL bands, an LDL score was calculated for each subject, with the relative area in each band taken into consideration. Four major LDL particle size groups were classified in the present studies: large LDL, intermediate LDL, small LDL, and very small LDL. The use of beta-blockers was significantly associated with smaller LDL particles. After adjusting for use of this medication, small LDL particles were still more prevalent in CAD patients (39%) compared with controls (27%). The prevalence of large LDL particles was lower in CAD patients (3%) than in controls (24%). Intermediate LDL particles were the most prevalent in both groups, 49% in CAD patients and 46% in controls. The difference in LDL particle size between CAD patients and controls was not independent but was highly associated (p less than 0.0001) with elevated triglyceride levels and decreased high density lipoprotein (HDL) cholesterol levels. Significantly higher LDL cholesterol levels were found in subjects with intermediate and small LDL particles than in those with large or very small LDL particles.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECT OF GENDER, AGE, AND LIPID STATUS ON LOW DENSITY LIPOPROTEIN SUBFRACTION DISTRIBUTION. RESULTS FROM THE FRAMINGHAM OFFSPRING STUDY

The presence of low molecular weight low density lipoprotein ]LDLl[ particles in plasma has been associated with premature coronary artery disease. In this study we have examined factors affecting LDL subfraction distribution as determined by 2% to 16% polyacrylamide-agarose gradient gel electrophoresis of whole plasma in a normal, primarily middle-aged, population of adult male and female participants (n = 280, ages 25 to 75 years) in the Framingham Offspring Study. Seven major LDL bands (LDL-1 to LDL-7) were observed in different individuals, with most subjects having either one or two major bands. The presence of low molecular weight LDL (LDL-4 to LDL-7) in plasma as the predominant LDL type was significantly more common in men than in women (43.5% versus 14.8%, p < 0.001). The presence of low molecular weight LDL was correlated < 0.01) with increased age, plasma triglyceride, total cholesterol, very low density lipoprotein (VLDL) cholesterol, LDL cholesterol (in women only), and apolipoprotein (apo) B concentrations, as well as with decreased high density lipoprotein (HDL) cholesterol and apo A-I levels. Approximately 69% of the variability in LDL subfractions could be accounted for by alterations in plasma triglyceride and HDL cholesterol levels. These data are consistent with the concept that LDL subfraction distribution is influenced by gender and plasma lipoprotein levels and can be determined readily by the use of whole plasma.

LDL particle size distribution. Results from the Framingham Offspring Study.

Using 2-16% gradient gel electrophoresis, we examined low density lipoprotein (LDL) particle size in relation to plasma lipoproteins in 1,168 women and 1,172 men from the Framingham Offspring Study. In addition, we studied the effect of dietary intake on LDL size in a subset of the population. Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019-1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL5 in d = 1.038-1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml. Seventy-seven percent of the population had one major and at least one minor LDL peak. Secondary LDL peaks accounted for 23% of the total LDL relative area, based on laser scanning densitometry. LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL 1, 30% and of LDL 2, 31%), whereas men exhibited a more symmetric distribution (prevalence of LDL 3, 42%). The prevalence of small (< 255 A), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-I levels. In addition, we found a significant (p < 0.0001) association between LDL cholesterol and LDL size. The highest LDL cholesterol levels were found among women with LDL 4 (148 mg/dl) and men with LDL 3-5 (138 mg/dl). In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels. We also found that compared with subjects with optimal LDL cholesterol levels (< 130 mg/dl), individuals with high-risk LDL cholesterol levels (> or = 160 mg/dl) had 1) a higher prevalence of LDL 3 and 4 (women only) and a lower prevalence of LDL 1 and 2 (women only) and 2) 11% higher LDL cholesterol to apo B ratios, even when matched for LDL particle size. Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles. Therefore, the identification of small, dense LDL particles per se may not be a good indicator of coronary artery disease risk in population studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary Therapy in Hypertension

A 57-year-old woman is seen in an outpatient clinic, where her blood pressure reading is 155/95 mm Hg. Dietary therapy is recommended. Dietary changes that have been shown to reduce blood pressure include reduced sodium intake, reduced caloric intake (for weight loss), and diets high in fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, nuts, and unsaturated vegetable oils.

The use of fatty acid biomarkers to reflect dietary intake.

Purpose of review This review compares fatty acid biomarkers to assess compliance in dietary intervention trials with their application in epidemiological studies. Recent findings Although many studies have used fatty acid biomarkers to assess compliance in short-term dietary intervention trials and habitual diets in observational studies, there is little information on the reliability and comparability of these measures. In this review, we summarize the usefulness and limitations of fatty acid biomarkers in clinical and epidemiological studies. As there are very few recent publications in this area, a complete literature review is provided. Summary Several options are available for the biological assessment of dietary fatty acids. The type of study (short or long-term), the metabolic characteristics and expected variability in the fatty acids of interest are major considerations when determining which tissues reflect a better measure of true intake. Certain fatty acids may not be suitable to assess differences in intake under non-isocaloric conditions and when trying to identify small differences. Serum cholesterol ester is the most suitable serum fraction to assess short-term dietary compliance, but given the multiple factors that affect response, the quantification of compliance should be interpreted with caution. Adipose tissue is the biomarker of choice for long-term intake, but a preferred blood constituent (plasma versus erythrocytes) is difficult to establish given the data available to date. Future studies should explore the use of whole blood as an alternative choice to measure fatty acid intake in epidemiological studies.

α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND Prior studies of α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results. OBJECTIVE We conducted a meta-analysis to summarize the evidence regarding the relation of ALA and CVD risk. DESIGN We searched multiple electronic databases through January 2012 for studies that reported the association between ALA (assessed as dietary intake or as a biomarker in blood or adipose tissue) and CVD risk in prospective and retrospective studies. We pooled the multivariate-adjusted RRs comparing the top with the bottom tertile of ALA using random-effects meta-analysis, which allowed for between-study heterogeneity. RESULTS Twenty-seven original studies were identified, including 251,049 individuals and 15,327 CVD events. The overall pooled RR was 0.86 (95% CI: 0.77, 0.97; I² = 71.3%). The association was significant in 13 comparisons that used dietary ALA as the exposure (pooled RR: 0.90; 95% CI: 0.81, 0.99; I² = 49.0%), with similar but nonsignificant trends in 17 comparisons in which ALA biomarkers were used as the exposure (pooled RR: 0.80; 95% CI: 0.63, 1.03; I² = 79.8%). An evaluation of mean participant age, study design (prospective compared with retrospective), exposure assessment (self-reported diet compared with biomarker), and outcome [fatal coronary heart disease (CHD), nonfatal CHD, total CHD, or stroke] showed that none were statistically significant sources of heterogeneity. CONCLUSIONS In observational studies, higher ALA exposure is associated with a moderately lower risk of CVD. The results were generally consistent for dietary and biomarker studies but were not statistically significant for biomarker studies. However, the high unexplained heterogeneity highlights the need for additional well-designed observational studies and large randomized clinical trials to evaluate the effects of ALA on CVD.

Association of the Trp719Arg Polymorphism in Kinesin-Like Protein 6 With Myocardial Infarction and Coronary Heart Disease in 2 Prospective Trials The CARE and WOSCOPS Trials

OBJECTIVES We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment. BACKGROUND Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology. METHODS We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial. RESULTS We found that Trp719Arg (rs20455) in KIF6 was associated with coronary events. KIF6 encodes kinesin-like protein 6, a member of the molecular motor superfamily. In placebo-treated patients, carriers of the KIF6 719Arg allele (59.4% of the CARE trial cohort) had a hazard ratio of 1.50 (95% confidence interval [CI] 1.05 to 2.15) in the CARE trial and an odds ratio of 1.55 (95% CI 1.14 to 2.09) in the WOSCOPS trial. Among carriers, the absolute risk reduction by pravastatin was 4.89% (95% CI 1.81% to 7.97%) in the CARE trial and 5.49% (95% CI 3.52% to 7.46%) in the WOSCOPS trial. CONCLUSIONS In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.

LDL Containing Apolipoprotein CIII Is an Independent Risk Factor for Coronary Events in Diabetic Patients

Objective—Triglyceride-rich lipoproteins that contain apolipoprotein CIII (apoCIII) are prominent in diabetic dyslipidemia. We hypothesized that these lipoproteins increase coronary disease risk in diabetic patients beyond that caused by standard lipid risk factors. Methods and Results—Diabetic patients with previous myocardial infarction were followed for 5 years, and 121 who had a recurrent coronary event were matched to 121 who did not. VLDL and LDL that contained or did not contain apoCIII (CIII+ or CIII−) were prepared by immunoaffinity chromatography and ultracentrifugation. IDL was included in the LDL fraction. LDL CIII+, rich in cholesterol and triglyceride, was the strongest predictor of coronary events (relative risk [RR] 6.6, P <0.0001, for 4th versus 1st quartile). LDL CIII+ comprised 10% of total LDL. The main type of LDL, LDL CIII−, was less strongly predictive (RR 2.2, P =0.07). The increased risk associated with LDL CIII+ was unaffected by adjustment for plasma lipids, apoB, non-HDL cholesterol, or the other VLDL and LDL types. For VLDL CIII+, RR 0.5, P =0.07; for VLDL CIII−, RR 2.3, P =0.046. The presence of apolipoprotein E with CIII on VLDL and LDL did not affect risk. Conclusions—LDL with apoCIII strongly predicts coronary events in diabetic patients independently of other lipids and may be an atherogenic remnant of triglyceride-rich VLDL metabolism.

A Prospective Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk

Background: Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings. Methods: A nested case-control study was conducted among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Conditional logistic regression was used to estimate the relative risks (RR) and 95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and Gleason < 7) and aggressive (stage C/D, Gleason ≥ 7, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific fatty acids expressed as percentages of total fatty acids. Results: Whole blood levels of all long-chain n-3 fatty acids examined and of linoleic acid were inversely related to overall prostate cancer risk (RRQ5vs.Q1, 0.59; 95% CI, 0.38-0.93; Ptrend = 0.01 for total long-chain n-3 fatty acids and RRQ5vs.Q1, 0.62; 95% CI, 0.41-0.95; Ptrend = 0.03 for linoleic). Blood levels of γ-linolenic and dihomo-γ-linolenic acids, fatty acids resulting from the metabolism of linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI, 0.94-2.12; Ptrend = 0.05 for γ-linolenic and RR, 1.54; 95% CI, 1.03-2.30; Ptrend = 0.02 for dihomo-γ-linolenic acid). Levels of arachidonic and α-linolenic acids were unrelated to prostate cancer. Conclusions: Higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer. The direct associations of linoleic acid metabolites with prostate cancer risk deserve further investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1364–70)

Adipose Tissue α-Linolenic Acid and Nonfatal Acute Myocardial Infarction in Costa Rica

Background—&agr;-Linolenic acid may protect against cardiovascular disease. We examined the association between adipose tissue &agr;-linolenic acid and nonfatal acute myocardial infarction (MI) in a population-based case-control study in Costa Rica. Methods and Results—The 482 case patients with a first nonfatal acute MI and 482 population control subjects were matched by age, sex, and area of residence. Fatty acids were assessed by gas-liquid chromatography in adipose tissue samples collected from all subjects. ORs and 95% CIs were calculated from multivariate conditional logistic regression models. Subjects in the top quintiles of adipose tissue &agr;-linolenic acid had a lower risk of MI than those in the lowest quintile: OR (95% CI), 1.00; 0.80 (0.52 to 1.24); 0.53 (0.34 to 0.82); 0.44 (0.28 to 0.67); and 0.37 (0.24 to 0.59); test for trend, P <0.0001. This association was strengthened after adjustment for established MI risk factors, including smoking, physical activity, income, and adipose tissue linoleic acid and trans fatty acids (OR for the top versus lowest quintile, 0.23; 95% CI, 0.10 to 0.50; test for trend, P <0.0001). Further adjustment for the intake of saturated fat, fiber, alcohol, and vitamin E did not change this association (OR for the top versus lowest quintile, 0.23; 95% CI, 0.10 to 0.55; test for trend, P <0.0001). Conclusions—The inverse association observed between &agr;-linolenic acid and nonfatal acute MI suggests that consumption of vegetable oils rich in &agr;-linolenic acid confers important protection against cardiovascular disease.