Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. METHODS AND RESULTS: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality. CONCLUSIONS: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

Pioglitazone improves the cardiovascular profile in patients with uncomplicated systemic lupus erythematosus: a double-blind randomized clinical trial.

OBJECTIVE: We studied the effect of pioglitazone on insulin levels, inflammation markers, high-density lipoprotein (HDL) composition and subclasses distribution, in young women with uncomplicated systemic lupus erythematosus (SLE). METHODS: This double-blind trial included 30 premenopausal women (30 ±8 years old) with SLE, who were randomized to pioglitazone (30 mg/day) or placebo treatment for 3 months. Plasma and HDL lipids were determined by colorimetric enzymatic assays, insulin by radioimmunometric assay, inflammation by immunonephelometry and HDL size and subclasses distribution by a native 4-30% polyacrylamide gradient gel electrophoresis. RESULTS: Compared with placebo, pioglitazone significantly increased HDL-cholesterol plasma levels (14.2%), reduced fasting insulin plasma levels (23.6%) and the homeostasis model assessment-insulin resistance (31.7%). C-reactive protein (70.9%) and serum amyloid A (34.9%) were also significantly reduced with the pioglitazone use, whereas the HDL particle size was increased (8.80 nm vs. 8.95 nm; p = 0.044) by changes in the distribution of HDL(2b), HDL(3b), and HDL(3c) subclasses. The change in HDL size correlated with a rise in free and cholesterol-ester content in the HDL particles. CONCLUSION: Pioglitazone significantly enhanced insulin sensitivity, reduced inflammation, and modified HDL characteristics, suggesting a potential beneficial effect of this drug in patients with SLE with a risk to develop cardiovascular disease. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov Protocol Registration System, with the number NCT01322308.

Effects of single sessions of low-intensity continuous and moderate-intensity intermittent exercise on blood lipids in the same endurance runners.

The factors responsible for the acute effects of exercise on blood lipids are not well known, and there have been few studies comparing different kinds of exercise in the same population. The concentration of blood lipids was evaluated in this study at the end and at post-24h of two 14km/90min single exercise sessions: continuous exercise (CE) at 44.5+/-5.6% VO(2max) and intermittent exercise (IE) at 39-72% VO(2max), in subjects with high levels of aerobic training. Fourteen male athletes (endurance runners) took part in this study and each completed a 24h dietary record. The O(2) uptake and CO(2) production were recorded, and blood lactate and blood lipids were measured. The results showed that triacylglycerols were not modified by any kind of exercise. Total cholesterol was increased at the end of both exercises: 7.04% for CE (p<0.001) and 4.23% for IE (p=0.001). High-density lipoprotein cholesterol was increased at the end of IE: 11.38% (p=0.03) and low-density lipoprotein cholesterol was increased only at the end of CE: 7.45% (p=0.006). The increase of lipids for CE was negatively correlated with aerobic fitness indicators (heart rate and %HRmax at lactate threshold), and was positively associated with energy expenditure. For IE, %HRmax and lactate were negatively correlated, and the respiratory exchange ratio was positively correlated, with the lipid increase. We conclude that in trained male athletes, a 14km run in 90min induced different changes of lipid profile if the exercise was done continuously or intermittently, and that in CE the extent of these increases was influenced by aerobic fitness.

High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus.

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL(2b) (-14.7%) and higher proportions of HDL(3b) (+8.8%) and HDL(3c) (+23.3%). Cholesteryl ester (-18%) and apolipoprotein AI (-9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL (P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R(2) = 0.327) and plasma total apo AI (R(2) = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.

C-reactive protein levels and their relationship with metabolic syndrome and insulin resistance in Mexican adolescents.

OBJECTIVE: To investigate the relationship of high sensitive C-reactive protein (hs-CRP) with metabolic syndrome components and insulin resistance in Mexican adolescents. METHODS: 325 adolescents, 182 girls and 143 boys, aged 12-16 years were studied. Standardized clinical measurements and plasma lipids, glucose, insulin and hs-CRP were determined. For metabolic syndrome (MS), the NCEP-ATP III definition was used. RESULTS: MS prevalence was 13%. The most frequent MS components were low HDL-C (50%), high triglycerides (35%), and high waist circumference (28%). hs-CRP median and 75th percentile values for all children were 0.42 and 0.97 mg/dl, respectively. The highest values of hs-CRP were found in children who had MS, p <0.007. hs-CRP was positively correlated with waist circumference, triglycerides, and negatively with HDL-C, p <0.01, and positively with insulin, p <0.001. In stepwise multiple regression analysis, body mass index and HOMA-IR accounted for 10.4% and 12.7% of hs-CRP levels, respectively. CONCLUSIONS: Body mass index and insulin resistance have an independent effect on high hs-CRP levels, and explain a large part of hs-CRP concentrations in adolescents. Central adipose tissue might induce an inflammatory state that could be identified from adolescence.

Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations.

BACKGROUND: Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin binding with plasminogen, inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a) have been reported in several populations. AIM: The study examined the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. METHODS: We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin binding by immuno-enzymatic assay and short tandem repeat (STR) polymorphic marker genetic analysis by capillary electrophoresis. RESULTS: Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg dL(-1)) relative to Mazahuas (8.2 mg dL(-1)), Mayas (8.25 mg dL(-1)) and Mayos (6.5 mg dL(-1)). Phenotype distribution was different in Mayas and Mazahuas as compared with the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. CONCLUSION: There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in the Native Mexican and the Mestizo group.

Association of visceral fat with coronary risk factors in a population-based sample of postmenopausal women.

OBJECTIVE: To investigate in a population-based random sample of postmenopausal women the adjusted association of visceral adipose tissue (VAT) with coronary risk factors. DESIGN: Cross-sectional population-based random sample study. SUBJECTS: Ninety-eight postmenopausal women (age 50-65 y). MEASUREMENTS: Visceral and subcutaneous fat areas by computer axial tomography, anthropometry, lipid profile, fasting glucose and insulin, diet, physical activity, smoking status and alcohol intake. RESULTS: Compared to women with low VAT, women with high VAT (>117.8 cm(2)) had a less favorable metabolic profile with significantly higher fasting glucose (120+/-50 vs 98+/-39), insulin (7.9+/-10 vs 5+/-8), triglycerides (172+/-69 vs 127+/-72), apolipoprotein B (119+/-24 vs 98+/-32) and significantly lower HDL-C (38+/-10 vs 46+/-14) values in the whole sample (n=98). A similar profile was found in women without diabetes and hypertension (n=39). In multiple regression models, VAT explained a portion of the variance of TG (6.2%) in the entire sample and of total cholesterol (12.4%), LDL-C (15.8%), triglycerides (16.3%), apolipoprotein B (11.6%), and fasting glucose (28.4%) in the group of non-diabetic or hypertensive women. Our VAT cut-off point of 117.8 cm(2) corresponded to a waist circumference of 84 cm. CONCLUSION: Our results in a random population-based sample of postmenopausal women confirm the association of VAT with most coronary risk factors. These associations persisted after adjusting for diet, physical activity, smoking status and alcohol intake.

[Fibrates in the secondary prevention of ischemic cardiopathy]. / Fibratos en la prevención secundaria de cardiopatía isquémica.

Clinical trials have demonstrated that reduction of low density lipoprotein cholesterol (LDL-C) reduces the incidence of major cardiac events in patients with coronary heart disease (CHD). Recently, two major secondary prevention trials that evaluated the impact of increasing low serum levels of high density lipoprotein cholesterol (HDL-C) and decreasing serum triglycerides on cardiovascular morbidity and mortality were published. This paper briefly summarizes the characteristics and results of these two studies. In the veterans Affairs HDL Intervention Study (VA-HIT), LDL-C was not changed; HDL-C increased 6.0% and triglycerides were reduced 31% by gemfibrozil. The lipid changes in the Bezafibrate Infarction Prevention (BIP) study were LDL-C -6.5%, HDL-C 18%; and triglycerides -21%. In VA-HIT, there was a 22% reduction (p = 0.006) in major CHD events, whereas in the BIP study a nonsignificant reduction of only 9.4% was observed. It is not clear why the effectiveness of fibrate therapy was different in the two studies. From these results it has been suggested that for most CHD patients, the 3-hydroxy-3-methylghutaryl coenzyme A reductase inhibitors (statins) will remain the initial drugs of choice, but fibrates may be of use in a subgroup of patients.

LDL size and susceptibility to oxidation in experimental nephrosis.

The aim of this study was to investigate the relationship between endothelial dysfunction and low density lipoprotein (LDL) size and susceptibility to oxidation in nephrotic rats with or without deficiency of vitamin E and selenium. Four groups of male Wistar rats were studied: control (C), vitamin E and selenium deficient control (DefC), nephrotic (NS), and vitamin E and selenium deficient NS (DefNS). Nephrotic syndrome was induced by puromycin aminonucleoside. The molar ratio of vitamin E/LDL-cholesterol was significantly lower in DefNS, DefC rats, and NS vs. C rats. In comparison with control animals, vasodilation and LDL oxidability were significantly lower in nephrotic animals. LDL size was similar in all groups. Abnormal endothelial function in response to acetylcholine and carbachol was observed in NS animals compared to control rats. Relaxation response was inversely associated with an increase in LDL susceptibility to oxidation and with a lower molar ratio of vitamin E/LDL-c. LDL oxidability and LDL-c were the only variables independently associated with vasodilation. These results suggest that endothelial dysfunction of NS may be a consequence of the increased LDL susceptibility to oxidation, secondary to antioxidant deficiency.

Differential effects of obesity with and without hyperinsulinemia on plasma lipoprotein(a) concentrations in men.

To determine the association of in vivo concentrations of insulin, obesity, and gender with lipoprotein(a) [Lp(a)] levels, we used a cross-sectional population-based survey of a multistage random sample of the Mexico City adult population. We studied 423 normoglycemic, normotensive subjects from an original sample of 825, comprised of 239 men and 189 women with a mean age of 38.6 years (range, 17 to 90). All subjects were divided into 8 groups according to body mass index, fasting insulin, and gender. Lp(a) concentrations (mg/dL) were similar in obese women with and without high insulin levels (19.9 v 18.6), but hyperinsulinemic obese men had significantly lower Lp(a) levels than normoinsulinemic obese men (7.9 v 29.4). In addition, the proportion of obese men with Lp(a) concentrations of > or = 30 mg/dL was significantly higher in the normoinsulinemic than in the hyperinsulinemic (29.2% v 0.0%). The frequency distribution of Lp(a) levels was shifted to a lower range in hyperinsulinemic men compared with normoinsulinemic men. Our results show that in men, hyperinsulinemic obesity is associated with low Lp(a) levels, while obesity with normoinsulinemia is related to increased Lp(a) concentration. These observations were not found in women. These findings may explain the conflicting results reported by several studies.

Influence of the apolipoprotein E polymorphism on plasma lipoproteins in a Mexican population.

The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 278 Mexican individuals. The most frequent genotype was E3/3 (80.5%) followed by E3/4 (12.5%), E2/3 (5.0%), E2/4 (1.4%), and E4/4 (0.3%). Our data are similar to those previously described for Mexican-American and American Indian populations, which show the highest frequency worldwide of the APOE*3 and the E3/3 genotype. Compared to female carriers of the E3/3 genotype, women with the E3/4 genotype presented increased low-density lipoprotein cholesterol (117 +/- 28.0 mg/dL vs. 134.0 +/- 31.7 mg/dL, p < 0.05), and total cholesterol (179.4 +/- 33.4 mg/dL vs. 197.5 +/- 35.4 mg/dL, p < 0.01). Also, we detected increased high-density lipoprotein concentrations in women with the E2/3 genotype (53.7 +/- 19.5 mg/dL) when compared to women with the E3/3 genotype (45.2 +/- 12.0 mg/dL) (p < 0.032). Our data suggest that genetic variation at the APOE locus in the Mexican population is a genetic factor that influences plasma lipid levels. This effect was observed only in the female population. Additional studies attempting to correlate APOE polymorphism with plasma lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Mexican population.

Changes in symptoms, lipid and hormone levels after the administration of a cream with phytoestrogens in the Climacteric--preliminary report.

OBJECTIVE: To establish the changes in lipid and hormone levels, as well as in symptoms, after topical application of a cream with phytoestrogens in postmenopausal women. METHODS: 30 postmenopausal women were studied. At baseline and 1 month after the beginning of treatment, levels of FSH, estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone, total cholesterol, HDL-C, LDL-C, and triglycerides were measured. Climacteric symptoms were evaluated with a modified Kupperman's index (KI). The subjects received a cream with phytoestrogens (n = 15) or placebo (cold cream) (n = 15) in a randomized, double-blind manner. Statistically significant differences were determined by Student's t test. RESULTS: No differences were found in hormones, lipids, or in KI between the groups. When comparing each group separately, only a significant decrease in KI was found, in both groups, at the end of the treatment. CONCLUSIONS: This cream with phytoestrogens had an effect only in climacteric symptoms, but similar to the placebo. The lack of effect in the other variables was probably due to the administration route, or to a lack of effect of this product.

[Efficacy and safety of immediate-release niacin in patients with ischemic cardiopathy. Experience of the Instituto Nacional de Cardiología "Ignacio Chávez"]. / Eficacia y seguridad de la niacina de liberación inmediata en pacientes con cardiopatía isquémica. Experiencia del Instituto Nacional de Cardiología "Ignacio Chávez".

UNLABELLED: Primary and secondary prevention trials have demonstrated that niacin improves the lipid profile and reduces coronary morbidity and mortality. OBJECTIVE: To investigate the safety and efficacy of niacin in daily doses of 1.5 and 3.0 g in patients with ischemic heart disease and dyslipidemia. PATIENTS AND METHODS: Sixty one male and female patients, aged 30 to 70 years were included. Thirty two patients were later excluded; 18 for adverse events and 14 for causes not related to niacin. RESULTS: In the 29 patients that finished the study, niacin in a dose-dependent manner, significantly reduced the levels of total cholesterol, LDL-cholesterol, triglycerides, apoB and LDL-C/HDL-C ratio, and significantly increased HDL-Cholesterol concentrations; a decrease in lipoprotein(a) was observed with both dosages, but the change was significant only with the 3.0 g/day. In 11 patients (38%) lipids and lipoproteins reached ideal concentrations. In 15 patients (52%) C-LDL/C-HDL was lower than or equal to 3.5 at the end of the study. CONCLUSIONS: Our results suggest that niacin is well tolerated by 62% of the patients. Niacin is a safe, effective and a low cost alternative in the treatment of patients with ischemic heart disease and dyslipidemia.

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of

Effect of the new diagnostic criteria for diabetes in the Mexico City study.

OBJECTIVE: To assess the effect of the new American Diabetes Association (ADA) diagnostic criteria for diabetes in the Mexico City survey. METHODS: The data available from the Mexico City study were included. This cross-sectional survey was conducted from January 1991 to March 1992 and involved 805 adults (20 years of age or older; mean age, 41 years). Survey procedures and results were previously published. Of the residents with diabetes, 74.2% had a previous diagnosis, and 25.8% were diagnosed on the basis of fasting plasma glucose (FPG) levels obtained during the survey. For the current report, these data were reanalyzed on the basis of the new ADA diagnostic criteria. RESULTS: The prevalence of newly diagnosed diabetes with use of the old and the new criteria was 23.1% versus 32.3% in men (P = 0.31) and 27.5% versus 36.3% in women (P = 0.32), respectively. The crude prevalence rate of diabetes increased from 8.7% to 9.3% (P = 0.42), and the age-adjusted rate increased from 10.6% to 11.2% for women (P = 0.64) and from 6.0% to 6.5% for men (P = 0.49). The prevalence of impaired FPG was 4.8%. Those patients with impaired FPG or newly diagnosed diabetes with FPG levels between 126 and 140 mg/dL had a more atherogenic risk profile than did those with normal carbohydrate metabolism. CONCLUSION: On the basis of the 1990 population census in Mexico City, the new ADA criteria will add 28,331 patients with diabetes (6.9%) to an already insufficient medical system. For those patients with impaired FPG or newly diagnosed diabetes on the basis of the new criteria, management should be focused on the control of the diverse and highly prevalent coronary risk factors.

[Lipoprotein(a) and lipids in chronic renal insufficiency and kidney transplant]. / Lipoproteína(a) y lípidos en insuficiencia renal crónica y en trasplante renal.

OBJECTIVE: To establish the prevalence of lipid and lipoprotein (a) abnormalities in patients under hemodialysis or who underwent renal transplantation. METHODS: Forty dialyzed patients, 64 transplanted and a comparison group of 77 subjects of the general population paired by gender and age were studied. RESULTS: The most prevalent disorder in the hemodialysis was hypoalfalipoproteinemia followed by Lp(a) excess while the least common disorder was hypercholesterolemia. The transplanted patients had the lowest prevalence of Lp(a) excess and a higher proportion of hypercholesterolemia when compared to hemodialysis patients but similar to that of controls. CONCLUSION: Our results confirmed some previous findings observations of others but differed in that hypoalfalipoproteinemia and not hypertriglyceridemia was the predominant abnormality in the hemodialysis patients.

Improved metabolic control does not change plasma lipoprotein(a) levels in adolescents with type 1 diabetes mellitus.

BACKGROUND: It has been found that lipoprotein(a)[Lp(a)] is an independent risk factor for coronary heart disease. Studies on the influence of metabolic control on plasma Lp(a) levels in Type 1 diabetics have reported conflicting results. The aim of this study was to investigate Lp(a) levels in carefully selected adolescents with Type 1 diabetes mellitus before and after improved metabolic control achieved during a 2-week Juvenile Diabetes Training Camp. METHODS: Patients with conditions that affect plasma Lp(a) concentrations were not included. Metabolic variables were determined at the beginning and at the end of the camp. Diet was designed to supply 40-60 Kcal/Kg/day. Physical exercise was performed in two 60-minute daily sessions. Intermediate action insulin was given twice daily, and rapid acting insulin was also administered to some patients. RESULTS: On the last day of the camp, fructosamine declined from 430-362.7 mg/dL (p < 0.001), mean levels of total cholesterol, LDL-cholesterol, and triglycerides also declined significantly (p < 0.001), and HDL-C increased (p < 0.05). In contrast, no significant changes in plasma Lp(a) concentrations were observed. CONCLUSIONS: The findings of this study in this relatively large group of well-defined adolescents with Type 1 diabetes mellitus suggest that improved metabolic control does not reduce plasma Lp(a) levels.

Prevalence of high blood pressure and associated coronary risk factors in an adult population of Mexico City.

BACKGROUND: Several studies have addressed arterial hypertension prevalence in Mexico. However, few include an analysis of other types of hypertension and their associated risk factors. The present work describes the prevalence of high blood pressure (HBP), isolated systolic hypertension (ISH) and diastolic hypertension (DH) and their association to certain risk factors of cardiovascular disease in an adult population of Mexico City. METHODS: A cross-sectional study was performed on 825 subjects aged between 20 and 90 years, selected by multistage cluster sampling. HBP was diagnosed by previous history if systolic blood pressure was > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg. The measurements taken included body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, levels of insulin, glucose, trigylycerides, total cholesterol, high and low density lipoprotein cholesterol, and lipoprotein(a). RESULTS: Prevalence adjusted by age for HBP was 19.4%, for ISH, 4.7%, and for DH, 4.1%. Age had an important influence on HBP and ISH with a highly significant X2t. The profile of metabolic variables was modified according to sex and type of hypertension. Thus, in DH, metabolic variables were more affected than in other types of hypertension. CONCLUSIONS: Results in HBP prevalence in the present study were lower than in other surveys performed in Mexico. It must be noted, however, that much care should be taken to choose the strategy of subject selection, since results of the prevalence of a disease depend on it to a great extent. The ISH and DH and their association to risk factors must be studied thoroughly because they constitute different clinical entities.