Increased carotid intima-media thickness in children-adolescents, and young adults with a parental history of premature myocardial infarction.

AIMS: The present study was designed to test whether early carotid structural changes are demonstrable (by high resolution B-mode ultrasound) in children, adolescents and young adults with a history of premature parental myocardial infarction. METHODS AND RESULTS: One hundred and fourteen healthy young (5 to 30 years) subjects with a parental history of premature myocardial infarction and 114 age- and sex-matched control subjects were enrolled in the study. They were divided into two age groups: children and adolescents (age 5 to 18 years) (54 individuals with a parental history of premature myocardial infarction and their control subjects; mean age 12.8+/-3.8 years) and young adults (age 19 to 30 years) (60 individuals with a parental history and their controls; mean age 23.8+/-3.3 years). All subjects underwent high resolution B-mode ultrasonographic evaluation of common carotid artery intima-media thickness. Lipid profile, resting blood pressure, body mass index and smoking status were also evaluated. In both age groups, compared to controls, subjects with a parental history of premature myocardial infarction had increased intima-media thickness of common carotid arteries (mean of combined sites: age 5-18 years: 0.45+/-0.076 mm vs 0.40+/-0.066 mm in controls, P=0.008; age 19-30 years: 0.48+/-0.077 mm vs 0.45+/-0.078 mm in controls,P =0.007) Offspring of coronary patients showed an unfavourable lipid profile, however, the association between a parental history of premature myocardial infarction and carotid intima-media thickness was independent of lipids, apolipoproteins and other traditional risk factors. CONCLUSIONS: Vascular structural changes associated with a parental history of premature myocardial infarction are already detectable in childhood and adolescence and occur independently of several traditional cardiovascular risk factors.     

Parental history of premature myocardial infarction is a stronger predictor of increased carotid intima-media thickness than parental history of hypertension

An increased carotid intima-media thickness (IMT) is detectable in young subjects with parental history of premature myocardial infarction (PHPMI) or hypertension (PHH). In this study we evaluated if PHPMI and PHH exert a different influence on carotid IMT and if their conjunction produces additive effects.High-resolution B-mode ultrasonographic evaluation of common carotid artery IMT was acquired from 48 subjects without PHPMI and PHH (22 males, 26 females; mean age 22.1 ± 4.9 years; controls), 24 age- (±1 year) and sex-matched subjects with PHH without PHPMI (PHH-positive/PHPMI-negative subjects), 24 age- and sex-matched subjects with PHPMI without PHH (PHH-negative/PHPMI-positive subjects) and 24 age- and sex-matched subjects with both PHPMI and PHH (PHH/PHPMI-positive subjects). Lipid profile, resting blood pressure, smoking behaviour and body mass index (BMI) were also assessed. Carotid IMT was smaller in controls (0.41 ± 0.07 mm) compared to PHH-positive/PHPMI-negative subjects (0.47 ± 0.10, p = 0.023), to PHH-negative/PHPMI-positive subjects (0.54 ± 0.11, p < 0.001) and to PHH/PHPMI-positive subjects (0.52 ± 0.10 mm, p < 0.001). Carotid IMT was greater in PHH-negative/PHPMI-positive (p = 0.006) and in PHH/PHPMI-positive (p = 0.031) than in PHH-positive/PHPMI-negative subjects. No difference in carotid IMT was evident between PHH-negative/PHPMI-positive and PHH/PHPMI-positive subjects (p = 0.549). In the comparison among subjects using multiple regression analysis, only PHPMI, age and BMI were independently associated with carotid IMT.In healthy young subjects with PHPMI and/or PHH, carotid IMT is increased. PHPMI is a stronger predictor of increased carotid IMT than PHH. PHH in conjunction with PHPMI does not add any further detrimental effect on carotid IMT.     

Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives.

BACKGROUND: Studies among emigrant Indians have stressed the role of a powerful genetic factor, lipoprotein (a), in the causation of premature coronary artery disease. This study was carried out to assess lipoprotein (a) and lipid levels in 50 consecutive young north Indian patients (age less than 45 years, mean age 39+/-3.7 years) with myocardial infarction, their first-degree relatives (n=125, mean age 36+/-16 years), and age- and sex-matched controls (n=50, mean age 34+/-6.9 years). METHODS AND RESULTS: Blood samples for lipid estimation were taken within 24 hours of myocardial infarction and after overnight fasting for twelve hours. Lipoprotein (a) levels were estimated by the ELISA technique using preformed antibodies while lipid levels were estimated by kits using the colorimetric method. All were male patients. The mean lipoprotein (a) level was 22.28+5.4 mg/dl in patients, 13.88+5.19 mg/dl in their first-degree relatives and 9.28+22.59 mg/dl in controls. In addition, it was significantly higher in young patients with myocardial infarction and their relatives as compared to controls (p<0.001 for patients v. controls and p<0.05 for relatives v. controls). There was no significant difference in the levels of total cholesterol and low-density lipoprotein cholesterol among the three groups. High-density lipoprotein cholesterol was significantly lower in young patients with myocardial infarction (30.16+/-9.45 mg/dl) and their first-degree relatives (33.28+/-8.45 mg/dl) as compared to controls (46.8+/-8.04 mg/dl) (p<0.001 for patients v. controls and p<0.01 for relatives v. controls). Triglyceride levels were significantly higher in patients as compared to controls (202+/-76 mg/dl v. 149 + 82.99 mg/dl, p<0.05). Smoking was more prevalent in young patients with myocardial infarction as compared to controls (44% v. 36%, p<0.05). CONCLUSIONS: Smoking, high lipoprotein (a) and triglyceride levels and low high-density lipoprotein levels may be important risk factors for coronary artery disease in the younger population; also, there is familial clustering of high lipoprotein (a) levels in first-degree relatives of young patients with myocardial infarction.     

Endothelium-dependent vasodilation is impaired in apparently healthy subjects with a family history of myocardial infarction

OBJECTIVES: To investigate whether endothelial-dependent vasodilation is altered in healthy subjects with a family history of myocardial infarction. SETTING: Tertiary University Hospital SUBJECTS AND DESIGN: Fifty apparently healthy subjects selected from the general population were subjected to an evaluation of endothelial-dependent vasodilation (EDV) and endothelial-independent vasodilation (EIDV) by means of local infusion of methacholine (MCh, 2 and 4 microg/min) and sodium nitroprusside (SNP, 5 and 10 microg/min) with measurements of forearm blood flow with venous occlusion plethysmography. The occurrence of plaque and the intima-media thickness of the carotid arteries were determined by ultrasonography. RESULTS: Subjects reporting at least one parent suffering from myocardial infarction (n = 11) showed a significantly lower EDV than subjects without such a family history (21 +/- 3.7 vs. 26 +/- 6.7 ml/min/100 ml tissue at MCh 4 microg/min, P<0.05). EIDV was not significantly different between the groups (21 +/- 6.8 vs. 18 +/- 5.4 ml/min/100 ml tissue at SNP 10 microg/min). Age, sex distribution, body mass index, waist to hip ratio, blood pressure, lipids, fasting blood glucose, smoking habits and status of the carotid arteries were not significantly different between the groups. CONCLUSION: A family history of myocardial infarction was found to be associated with an impaired endothelial-dependent vasodilation in the forearm of apparently healthy subjects. The risk factor profile was not different from the control group, suggesting that genetic factors are responsible for the impaired endothelial-dependent vasodilation.     

Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan–Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011–1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.     

Plasma fibrinogen levels are associated with a strong family history of myocardial infarction.

Family history of myocardial infarction (MI) is a known risk factor for coronary artery disease (CAD). The aim of the present study was to investigate whether there is a specific risk factor profile for CAD in individuals with a strong family history of MI occurring at any age. The Study of Health in Pomerania is a cross-sectional, population-based study in the north-east of Germany. A random sample was drawn from the population aged 20-79 years. From 3793 subjects with siblings, 34 (0.9%) reported a history of MI in at least one parent and one sibling. We matched these cases with 136 controls (1 : 4 matching for age, sex and presence of sibling). We then compared cases and controls with respect to known risk factors for MI. Subjects with a dual parental and sibling history of MI had higher plasma fibrinogen levels (3.5 versus 3.0 g/l, respectively), and also more often angina pectoris than the matched controls (P < 0.05). Multivariable analysis revealed an independent association between dual parental and sibling history of MI and plasma fibrinogen levels. We conclude that plasma fibrinogen levels may indicate an inheritable risk for CAD in subjects with a strong family history of MI.     

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Journal of Thrombosis and Thrombolysis - Introduction: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history...     

Arterial stiffness is increased in healthy subjects with a positive family history of hypertension

Abstract

A positive family history of hypertension is a risk factor for cardiovascular diseases. We investigated the value of pulse wave velocity (PWV) in healthy subjects with a positive family history of hypertension. 255 healthy subjects (M/F: 75/180) were divided into two groups according to without (group 1) or with (group 2) a positive family history of hypertension. Carotid-femoral pulse wave velocity (CF-PWV) was measured by Complior apparatus. Our results showed that CF-PWV was significantly higher in group 2 than in group 1 (7.90?±?1.31 versus 7.32?±?1.15?m/s, p?<?0.001). High-density lipoprotein cholesterol (HDL-C) was significantly higher in group 1 than in group 2. Multiple linear regressions showed that age, family history, GLU, and MAP were independent influencing factors of CF-PWV in the entire study group. Our present study showed PWV is significantly higher in healthy subjects with a positive family history of hypertension. Family history might play an important role in this process.     

Lipoprotein (a) as a predictor of myocardial infarction in middle-aged men

PURPOSE: Whether serum lipoprotein (a) [Lp(a)] levels are an independent risk factor for coronary heart disease has been controversial. We have investigated its status in a prospective population survey, the Second Northwick Park Heart Study. METHODS: We recruited 2,616 men 50 to 61 years old from nine primary care practices in the United Kingdom. Baseline serum Lp(a) levels were measured by enzyme-linked immunosorbent assay (ELISA) and were analyzed in 3 groups (<25th percentile, 25th to 75th percentile, and >75th percentile) to overcome the problem of some measurements falling below the threshold of the assay. Coronary end points included sudden cardiac death, acute myocardial infarction, silent myocardial infarction on the electrocardiogram, and coronary artery bypass surgery. RESULTS: During a mean of 6 years of follow-up, 121 men had coronary events. In a multivariate analysis that also adjusted for fibrinogen, Apo-A1, Apo-B, and triglyceride levels, we identified several independent risk factors for coronary events, including cholesterol level (hazard ratio [HR] = 1.5 per SD 95% confidence interval [CI] 1.3 to 1.8), diabetes (HR = 4.1, 95% CI: 2. 0 to 8.4), current versus never smoking (HR = 2.5, 95% CI: 1.5 to 4.1), diastolic blood pressure (HR = 1.4 per SD, 95% CI: 1.1 to 1.7), Apo-A1 (HR = 0.8 per SD, 95% CI: 0.6 to 0.9), age (HR = 1.3 per SD, 95% CI: 1.1 to 1.6), and Lp(a) (>26.3 mg/dL [75th percentile] versus <2.9 mg/dL [25th percentile], HR = 1.9, 95% CI: 1.1 to 3.3]. There was a statistically significant (P = 0.01) difference in risk between the three levels of Lp(a). CONCLUSIONS: We found that a high Lp(a) level was an independent predictor of the development of coronary heart disease in middle-aged men.     

Retinol-binding protein levels are increased in association with gonadotropin levels in healthy women

Recent studies have demonstrated an association between retinol-binding protein (RBP4) and insulin resistance. Retinol-binding protein is decreased in women and elevated in polycystic ovary syndrome. However, prior studies have not investigated the relationship between RBP4, gonadal steroids, and gonadotropins in healthy women. The aim of this study was to determine the RBP4 levels in a cohort of healthy women with a range of body mass indices and glucose tolerances to investigate the relationship between RBP4, gonadotropin levels, and menopausal status. Serum RBP4 levels were measured by enzyme-linked immunosorbent assay and quantitative Western blot in 88 healthy women (aged 24-59 years) from the general community in a cross-sectional study. Retinol-binding protein was higher in postmenopausal compared with premenopausal women (26.1 ± 2.1 vs 19.3 ± 0.5 μg/mL, P = .001). In univariate analysis, RBP4 was associated with follicle-stimulating hormone (r = 0.37, P = .0004), luteinizing hormone (r = 0.3, P = .005), and sex hormone-binding globulin (r = −0.24, P = .03) and trended to significance with estradiol (P = .09) but not with free testosterone or dehydroepiandrosterone sulfate. Retinol-binding protein was also associated with insulin at 2 hours during an oral glucose tolerance test (r = 0.24, P = .03) and the area under the curve for insulin during the oral glucose tolerance test (r = 0.26, P = .02). In multivariate regression modeling, both follicle-stimulating hormone (P = .03) and luteinizing hormone (P = .04) remained significantly associated with RBP4 after controlling for estradiol, sex hormone-binding globulin, insulin area under the curve, cholesterol, triglycerides, waist-to-hip ratio, and tumor necrosis factor α. Retinol-binding protein was not associated with inflammatory markers or with carotid intima-media thickness. Therefore, RBP4 is higher in postmenopausal women and is associated with gonadotropin concentrations in healthy women.     

Lipoprotein(a) concentrations in healthy subjects in the Dominican Republic. Comparison with Japanese.

Previous studies have shown that serum concentrations of lipoprotein(a) [Lp(a)] are markedly different among different ethnic groups. We examined the serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol and Lp(a) in apparently healthy subjects aged 20-69 years in Japan (n = 865) and the Dominican Republic (n = 1,893). Dominicans had significantly lower levels of total cholesterol and HDL cholesterol than Japanese. The distribution of Lp(a) concentrations were markedly skewed towards low levels in both Japanese and Dominicans. However, the mean Lp(a) concentration in Dominicans was approximately 2 times higher than in Japanese (21.7 +/- 23.7 vs 12.3 +/- 15.9 mg/dl, p < 0.001). This is possibly because the majority of Dominicans are of mixed Negroid and European blood.     

Lipoprotein (alpha) as a risk factor for myocardial infarction]

Serum lipoprotein (alpha) [Lp(alpha)]was determined in 105 cases of myocardial infarction survivors (MIS). Lp(alpha) level in MIS was much more elevated as compared with that in healthy subjects and in a hypertension group. Lp(alpha) had no relation with apolipoprotein B and AI, cholesterol, triglyceride and high density lipoprotein cholesterol. It may be a significant and independent risk factor for coronary heart disease.     

Lipoprotein (a) blood levels in unstable angina pectoris, acute myocardial infarction, and after thrombolytic therapy

Lipoprotein (a) [Lp(a)] appears to be involved in atherogenesis and in vitro studies have suggested that it may interfere with thrombolysis. In this study, Lp(a) serum levels were determined by radioimmunoassay in 124 patients with ischemic heart disease. Of these, 47 had acute myocardial infarction, 13 had unstable angina, and 64 were age-matched patients with stable angina. Of the 60 patients with acute coronary artery disease, 34 received thrombolysis and 26 did not. In addition to Lp(a), serum plasminogen, alpha 2 antiplasmin, fibrinogen, and D-dimer (cross-linked fibrin degradation products) levels were measured. These tests were repeated after 6 hours in patients with myocardial infarction and unstable angina. No significant difference was found for admission Lp(a) levels among patients with myocardial infarction (0.324 +/- 0.047 g/liter), unstable angina (0.435 +/- 0.123 g/liter) and stable angina (0.431 +/- 0.023 g/liter), between patients with myocardial infarction with or without thrombolytic treatment, nor between late and early measurements in patients with unstable angina and acute myocardial infarction. Plasminogen, alpha 2 antiplasmin and fibrinogen values decreased significantly after thrombolytic treatment. The size of this decrease correlated positively with higher Lp(a) blood levels (p less than 0.05). Patients with Lp(a) greater than 0.25 g/liter had a 66% decrease in fibrinogen and a 53% decrease in anti-plasmin, compared with 35 and 32%, respectively, in patients with Lp(a) level less than or equal to 0.25 g/liter (p less than 0.05). Plasminogen levels revealed a similar trend, with a 61% decrease for the higher values and a 45% decrease for the lower values.(ABSTRACT TRUNCATED AT 250 WORDS)