Rhobert W. Evans

Relationship of C-Reactive Protein to Risk of Cardiovascular Disease in the Elderly Results From the Cardiovascular Health Study and the Rural Health Promotion Project

Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Homocyst(e)ine and Risk of Cardiovascular Disease in the Multiple Risk Factor Intervention Trial

A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for up to 20 years, were analyzed for homocyst(e)ine. Cases involved nonfatal myocardial infarctions (MIs), identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease (CHD), monitored through 1990. The nonfatal MIs occurred within 7 years of sample collection, whereas the majority of CHD deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: MI cases, 12.6 mumol/L; MI controls, 13.1 mumol/L; CHD death cases, 12.8 mumol/L; and CHD controls, 12.7 mumol/L. Odds ratios versus quartile 1 for CHD deaths and MIs combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase protein (C-reactive protein). These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001).

Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum ☆ ☆☆ ★ ★★

OBJECTIVE We tested the hypothesis that serum free (nonesterified) fatty acid and triglyceride concentrations are increased in nulliparous women with preeclampsia relative to women with uncomplicated pregnancies and that these lipids decrease post partum, consistent with the known resolution of clinical symptoms. The relationships between serum concentrations of these lipids and the lipid peroxidation metabolite malondialdehyde were also examined. STUDY DESIGN Predelivery and 24 to 48 hour postpartum venous blood samples were collected from eight women with preeclampsia and nine women with uncomplicated pregnancies after an 8- to 10-hour fast. Sera were analyzed for concentrations of triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and malondialdehyde. RESULTS Antepartum serum triglyceride and free fatty acid concentrations were increased approximately twofold in women with preeclampsia relative to uncomplicated pregnancies (p <0.02 and 0.004, respectively). Total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations did not differ between groups. Concentrations of all lipids decreased significantly in both groups within 48 hours post partum. However, triglyceride and free fatty acid concentrations remained higher in women with preeclampsia (p<0.006, both variables). Triglyceride and free fatty acid concentrations correlated positively, both ante partum (R2 0.42, p<0.01) and post partum (R2 0.39, p<0.02). Antepartum concentrations of malondialdehyde were 50% higher in women with preeclampsia (p<0.01) and decreased post partum (p <0.02) but did not decrease in controls (p = 0.07). Antepartum serum triglycerides and free fatty acids correlated positively with malondialdehyde concentrations (R2 0.38, p <0.02, both cases). CONCLUSION Triglycerides and free fatty acids, but not cholesterol, are increased in preeclampsia and correlate with the lipid peroxidation metabolite malondialdehyde. We speculate that these interactions may contribute to endothelial cell dysfunction in preeclampsia.

Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese-American, and White Men : A Cross-Sectional Study

OBJECTIVES We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S. BACKGROUND Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect. METHODS A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids. RESULTS Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 mum, 95% confidence interval [CI]: 21 to 57mum, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 mum, 95% CI: -1 to 46 mum, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively). CONCLUSIONS Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.

Homocysteine, Vitamins, and Cardiovascular Disease

The significance of any association between cardiovascular disease and circulating homocysteine concentrations is attracting considerable attention. The normal activities of the transsulfuration and remethylation pathways maintain intracellular homocysteine levels within a narrow range, and the controlled release of homocysteine into blood results in blood measurements that provide an accurate index of homocysteine status. In the circulation, homocysteine is rapidly oxidized, and very little homocysteine remains in the reduced form. The majority of homocysteine forms a disulfide bridge with protein, and some reacts either with itself to produce homocystine or with cysteine to form the mixed disulfide cysteine-homocysteine.1 Most analytical procedures include a reduction step and do not distinguish between the reduced and various oxidized forms of homocysteine; thus, the analyte measured is referred to as homocyst(e)ine. The normal range is unclear but may fall between 5 and 15 μmol/L. Analyses of homocysteine usually involve fasting samples of either serum or plasma. The concentrations are higher in serum, and increases of ≈10% have been reported in the postprandial stage.2 Homocysteine levels also increase with age and are higher in men than in women. A variety of disease states and medications modify homocysteine concentrations, and notably, impaired renal function may greatly increase homocysteine levels.3 Measurement of homocysteine should avoid blood samples that have been stored at room temperature, because red blood cells may release homocysteine, causing an artifactual increase in extracellular homocysteine concentrations. A complicating aspect of homocysteine metabolism for cardiovascular studies is that homocysteine concentrations may increase after a myocardial infarction or a stroke. Critically, data are not available for samples obtained before and after an event. However, analysis of samples obtained at the time of a myocardial infarction and up to 180 days later indicated an increase in homocysteine concentration from 12.9±0.9 to 15.3±1.1 μmol/L.4 Similarly, …

Detection of conjugated diene isomers of linoleic acid in liver lipids of rats fed a choline-devoid diet indicates that the diet does not cause lipoperoxidation

Abstract Male and female F-344 rats were fed for 1 week choline-devoid or control choline-supplemented diets containing either 5% corn oil and 10% partially hydrogenated vegetable oils (PHO diets) or 15% corn oil (CO diets). HPLC/second derivative UV spectrophotometric analyses, combined with on-line atmospheric pressure ionization mass spectrometry, were used to determine whether conjugated diene isomers of linoleic acid (CLA), present in the diets, were assimilated into liver and adipose tissue lipids. The CLA content in the PHO diets was an order of magnitude greater than that in the CO diets. CLA were detected in the adipose tissue of all rats but in the liver of only rats fed the PHO diets. In adipose tissue, the CLA levels clearly reflected those present in the diets, and no sex differences, or differences between rats fed the choline-devoid or control diets were noted. In addition to CLA, conjugated linolenic and eicosatrienoic acids, arising probably from desaturation and elongation of CLA, were detected in the liver. The results provide evidence that the conjugated dienes detected in liver lipids of rats fed a PHO-containing choline-devoid diet are of dietary origin and do not reflect lipid peroxidation.

Longitudinal changes in serum lipids among HIV‐infected men on highly active antiretroviral therapy

The aim of the study was to describe longitudinal changes in serum lipids among HIV‐infected men receiving highly active antiretroviral therapy (HAART) with long‐term follow‐up.

Lipoprotein subclasses and coronary artery calcium in postmenopausal women from the healthy women study

Lipoprotein subclass levels may improve the prediction of cardiovascular disease (CAD) in individuals beyond the risk assessment provided by conventional enzymatically determined lipid levels. The objective of this study was to evaluate the associations between nuclear magnetic resonance (NMR) spectroscopy-determined lipoprotein subclasses and coronary calcification in postmenopausal women, and to determine whether the associations were independent of conventional lipid measures. Coronary artery calcification (CAC) was measured by electron beam computed tomography, and lipoprotein subclasses were determined by NMR spectroscopy (Liposcience, Inc., Raleigh, NC), in 286 healthy women (mean age = 61.7), at 8 years postmenopause. CAC was analyzed as categories 0, 1 to 99, and > or =100. The mean CAC was 53 (range, 0 to 1,175), and 54% of the women had 0 scores. Large high-density lipoprotein (HDL) was inversely associated with CAC category, but small HDL was not. All very low-density lipoprotein (VLDL) subclasses-small, medium, and large-were positively associated with CAC (p <0.01). Small low-density lipoprotein (LDL) was positively associated with CAC (p <0.01), but medium and large LDL were not. Smaller LDL particle size (p <0.01) and higher levels of LDL particles (p <0.001) were associated with higher CAC category. In separate ordinal logistic regression models, small LDL, LDL particles, and large VLDL were each positively associated (p <0.05) with higher CAC after adjustment for age, systolic blood pressure (SBP), current smoking, and conventional measures of LDL cholesterol, HDL cholesterol, and triglycerides. These results suggest that the measurement of lipoprotein subclasses may improve the prediction of CAD in postmenopausal women beyond that provided by the conventional lipid panel and CAD risk factors.

Cloned Transgenic Swine Via In Vitro Production and Cryopreservation

Abstract Ithas been notoriously difficult to successfully cryopreserve swine embryos, a task that has been even more difficult for in vitro-produced embryos. The first reproducible method of cryopreserving in vivo-produced swine embryos was after centrifugation and removal of the lipids. Here we report the adaptation of a similar process that permits the cryopreservation of in vitro-produced somatic cell nuclear transfer (SCNT) swine embryos. These embryos develop to the blastocyst stage and survive cryopreservation. Transfer of 163 cryopreserved SCNT embryos to two surrogates produced 10 piglets. Application of this technique may permit national and international movement of cloned transgenic swine embryos, storage until a suitable surrogate is available, or the long-term frozen storage of valuable genetics.