Paternal History Of Myocardial Infarction Research Articles

Sex-Specific Familial Clustering of Myocardial Infarction in Patients With Acute Coronary Syndromes

Family history of premature myocardial infarction (MI) in first-degree relatives is a risk factor for MI and an indication for primary prevention. Although excess mother-to-daughter "transmission" occurs in ischemic stroke, no published studies have considered sex-of-parent/sex-of-proband interactions in the heritability of MI. In a population-based study (Oxford Vascular Study) of all patients with acute coronary syndromes (ACS), irrespective of age, family history of all acute vascular events and related risk factors were analyzed by sex and age of both probands and first-degree relatives. Premature events were categorized as occurring at age <65 years. Of 835 probands with 1 or more ACS, 623 (420 men) had incident events and complete family history data. In probands with premature ACS, maternal history of both MI and of all vascular events were more common in female than male probands (odds ratio [OR], 2.25; 95% CI, 1.02 to 4.94; P=0.04 and OR, 3.03; 95% CI, 1.47 to 6.26; P=0.002, respectively). No such effect existed for paternal history (OR, 1.00; 95% CI, 0.46 to 2.10; P=0.99 and OR, 1.19; 95% CI, 0.58 to 2.43; P=0.63, respectively). Age at ACS in probands was highly correlated with age at MI in mothers (r=0.46, P<0.001), regardless of the proband's sex. Consequently, history of premature maternal MI was strongly associated with premature ACS and premature MI in female (OR, 10.52; 95% CI, 2.17 to 56.6; P=0.001 and OR, 7.31; 95% CI, 1.55 to 34.6; P=0.004, respectively) and male probands (OR, 3.88; 95% CI, 1.20 to 12.6; P=0.01 and OR, 3.63; 95% CI, 1.13 to 11.60; P=0.02, respectively). Important sex-of-parent/sex-of-proband interactions exist in the family history of MI in patients with ACS. Greater emphasis should be placed on maternal than paternal history of MI, particularly in women aged <65 years.

The association of telomere length with paternal history of premature myocardial infarction in the European Atherosclerosis Research Study II

Inter-individual variability in telomere length is highly heritable and has been correlated with risk of coronary heart disease (CHD). Our aim was to determine the association of mean leukocyte telomere length with paternal history of premature myocardial infarction (MI). Mean leukocyte telomere length was measured with real-time polymerase chain reactions in 369 male students (18–28 years) with a paternal history of MI before the age of 55, recruited from 14 European universities, serving as cases and 396 age-matched controls with no paternal history of CHD. Overall, cases had borderline significantly shorter mean length (~550 bp), adjusted for age and geographical region, than controls (p = 0.05). A significant difference in telomere length across the geographical regions of Europe was observed (p < 0.0001), with shorter mean length in the Baltic and South and the longest in the Middle. The case–control difference (∼2.24 kb) in mean length was highly significant only in the Baltic region (p < 0.0001). There is suggestive evidence that, in young men, the biological expression of a paternal history of premature MI is at least in part mediated through inherited short telomeres. The association with paternal history of MI is strongly seen only in the Baltic compared to the rest of Europe, but this is not explained by shorter telomere length in this region.Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-008-0347-x) contains supplementary material, which is available to authorized users.

The glucose response to an oral fat tolerance test in young men with a paternal history of premature myocardial infarction: possible early indication of insulin resistance. The EARS 2 study

Concentrations of cholesterol, triglycerides and glucose are higher in young men with a paternal history of premature myocardial infarction than in age- and sex-matched controls. To test the hypothesis that insulin resistance constitutes the biological expression of increased coronary risk in these subjects. A total of 407 male university students with a paternal history of premature myocardial infarction (cases) and 415 age- and sex-matched controls were investigated for differences in insulin sensitivity. Four methods of assessing insulin sensitivity were used: (i) insulin and glucose responses to an oral glucose tolerance test (OGTT); (ii) insulin and glucose responses to an oral fat tolerance test (OFTT); (iii) minimal modelling of insulin and glucose data from a frequent sample intravenous glucose tolerance test performed on a subset of 55 cases and 50 controls and (iv) homeostasis model assessment (HOMA) of insulin resistance. The OFTT glucose response discriminated between cases and controls, with a smaller fall in glucose in cases compared with controls. The negative area under the glucose curve (AUC) (mean [standard error of the mean (SEM)]) was -1.42 (0.09) mmol min/L in cases and -1.76 (0.09) in controls (P = 0.004). Peak height (mean [SEM]) was -0.65 (0.02) mmol/L in cases and -0.73 (0.02) in controls (P = 0.007). The insulin responses were similar in cases and controls. Insulin AUC (mean [SEM]) was 161 (10) mU min/L in cases and 148 (10) in controls (P = 0.34). This combination of findings suggests that insulin-stimulated glucose uptake was reduced in the cases. These findings were consistent across European regions. None of the other methods revealed any differences between cases and controls. In young men with a paternal history of myocardial infarction, an OFTT detects altered insulin sensitivity that is not identified by an OGTT, minimal modelling or HOMA.

Markers of risk in young offspring with paternal history of myocardial infarction

Coronary heart disease clusters within families, but there may be several reasons for this phenomenon to occur. A possible way to elucidate this is to study biological relatives of affected individuals. The aim of our study was thus to compare a number of clinical, metabolic, clotting and immunologic factors between offspring with paternal history of premature myocardial infarction and controls and to propose a model which could safely allow to identify the high risk subgroup among them. Sixty-nine offspring of both sexes mean age 18.1 years old (cases) and thirty-two frequency matched relative to age and gender controls were studied. Cases compared to controls had significantly increased diastolic blood pressure levels (74.0±9.9 vs. 67.4±8.3 mmHg, P=0.002), leptin plasma levels (11.8±10.8 vs. 6.8±3 ng/ml, P=0.046) and fibrinogen, plasminogen, fibrin degradation products and plasminogen activator inhibitor-1 plasma levels (306.6±52.5 vs. 280.6±28.9 mg%, P=0.03, 97.4±23.5 vs. 83.6±15 mg%, P=0.0007, 292.0±148.5 vs. 219.2±69.4 ng/ml, P=0.036, 14.7±5.3 vs. 8.7±3.1 I.U./ml, P=0.0001, respectively), while cases had significantly decreased HDL-cholesterol serum levels (45.9±12.5 vs. 50.5±8.8 mg%, P=0.03) and protein S plasma levels (89.9±17.5 vs. 101.3±13.7%, P=0.001). Our findings suggest that offspring of affected individuals may be considered as a high risk group for cardiovascular disease.

Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women

Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women

Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women.

Few studies have examined the effects of paternal and maternal history of myocardial infarction (MI), including age at MI, on cardiovascular disease (CVD) risk, particularly among women. We prospectively studied 22 071 men from the Physicians' Health Study and 39 876 women from the Women's Health Study with data on parental history and age at MI. Among men, 2654 CVD cases developed over 13.0 years; among women, 563 CVD cases occurred over 6.2 years. Compared with men with no parental history, only maternal, only paternal, and both maternal and paternal history of MI conferred relative risks (RRs) of CVD of 1.71, 1.40, and 1.85; among women, the respective RRs were 1.46, 1.15, and 2.05. For men, maternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years had RRs of 1.00, 1.88, 1.88, 1.67, and 1.17; for women, the RRs for maternal age at MI of <50, 50 to 59, and >/=60 years were 2.57, 1.33, and 1.52. Paternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years in men had RRs of 2.19, 1.64, 1.42, 1.16, and 0.92; in women, for paternal age at MI of <50, 50 to 59, and >/=60 years, the RRs were 1.63, 1.33, and 1.13. An early history of parental MI (<60 years) conferred a greater risk of CVD than did MI at older ages. However, an increased risk of CVD remained for maternal age at MI of 70 to 79 years in men and >/=60 years in women, which suggests that any maternal history of MI may be important.

Intestinal fatty acid binding protein polymorphism at codon 54 is not associated with postprandial responses to fat and glucose tolerance tests in healthy young Europeans. Results from EARS II participants

Polymorphism Ala54Thr of the intestinal fatty acid-binding protein 2 (FABP2) has been reported to have an effect on the protein's affinity for long chain fatty acids and to be associated with serum lipid and insulin levels in fasting and especially postprandial states. We wanted to test whether this genetic variation is associated with fasting and postprandial glucose, insulin or lipid levels in 666 male university students participating in the second European Atherosclerosis Study (EARS II). We also studied whether the subgroup of 330 students with paternal history of myocardial infarction (MI) before the age of 55 have different genotype distribution than 336 matched controls. Results: No difference in genotype distribution was observed between offspring with and without paternal history of MI or between populations from 11 European countries. The frequency of the threonine encoding allele was 0.276 in cases and 0.266 in controls. There were no differences in fasting or postprandial serum lipid, glucose or insulin levels between subjects having different genotypes. Conclusions: In this study FABP2 Ala54Thr polymorphism was not associated with lipid or glucose metabolism. In addition to environmental and genetic factors, selection of study population also may explain the difference between this and earlier studies.

Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study.

Hepatic lipase (HL), a triglyceride lipase found in liver, adrenals, testes, and ovaries, takes part in the uptake, remodeling, and function of lipoproteins including HDL, as well as VLDL and chylomicrons. In the present study, the genotype distribution of five HL polymorphisms (-C480T, V133V, T202T, L334F, T457T) and their association to plasma lipid values were investigated. The study participants included 92 students with paternal history of myocardial infarction before the age of 55 and 194 matched control subjects, ie, the Finnish participants of the European Atherosclerosis Research Study (EARS). The allele T of the HL polymorphism -C480T showed an association with elevated HDL, apoA-I, and LpA-I values (ANOVA P < .01). No difference in genotype distribution was observed in the offspring with and without paternal history of myocardial infarction.

Lipoprotein lipase variants D9N and N291S are associated with increased plasma triglyceride and lower high-density lipoprotein cholesterol concentrations: studies in the fasting and postprandial states: the European Atherosclerosis Research Studies.

Variations at the DNA level with moderate effects on biochemical variables may be important for the occurrence of disease at the population level, if they are common. Two mutations in the LPL gene, N9 and S291, are associated with variation in fasting plasma concentrations of HDL cholesterol (HDL-C) and triglycerides (TG). We investigated whether these mutants were more frequent in offspring of cases with premature coronary disease and analyzed the effects on fasting plasma lipids and postprandial TG. Students with and without paternal history of myocardial infarction (cases and control subjects [controls]) were studied in the European Atherosclerosis Research Studies I and II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not differ between cases and control subjects. The N9 mutation was identified in 4.2% of all subjects in EARS-I, and carriers had higher fasting TG levels (P<.001) than noncarriers. In an oral fat tolerance test, there were no differences in postprandial TG between carriers and noncarriers of the N9 allele. The S291 mutation was identified in 3.1% of all subjects in EARS-I, and carriers had lower fasting HDL-C levels (P<.005) than noncarriers. There was a significant interaction between S291 genotype and body mass index on fasting TG levels (P<.01). In the cases, carriers of the S291 allele had higher TG levels 6 hours postprandially (P<.04) than did noncarriers. The two LPL mutations are common and may predispose to elevated TG and decreased HDL-C concentrations, even in young subjects. In the case of the S291 mutation, this effect appears to be mediated via delayed postprandial TG clearance. Moreover, even moderate obesity potentiates the TG-raising and HDL-lowering effects associated with the S291 allele.

Apo(a) phenotypes and Lp(a) concentrations in offspring of men with and without myocardial infarction. The EARS Study. European Atherosclerosis Research Study.

In the European Atherosclerosis Research Study, genetic and environmental markers of risk of premature coronary heart disease were compared in offspring of men with and without myocardial infarction before the age of 55 years. Cases were 682 students with a paternal history of myocardial infarction, and control subjects were 1312 students without such a history. The students were enrolled in 14 universities in five European regions (Finland, Great Britain, and northern, middle, and southern Europe). Lipoprotein(a) [Lp(a)] concentrations were skewed towards lower concentrations in both cases (median, 7.3 mg/dL; 95% confidence interval, 6.3 to 8.1 mg/dL) and control subjects (median, 6.6 mg/dL; 95% confidence interval, 6.1 to 7.2 mg/dL) (P = .37). Significantly more northern European male cases than control subjects had Lp(a) levels exceeding 30 mg/dL (P = .040), but this did not pertain to females (P = .29), and overall, there was no difference between cases (16.5%) and control subjects (15.5%) in the frequency of Lp(a) concentrations above 30 mg/dL (P = .63). As expected, there was a significant (P < .01) inverse relationship between apo(a) molecular size and Lp(a) concentration. In Great Britain there was a significant difference in phenotype distribution between cases and control subjects (P = .035), due mainly to a high frequency of the apo(a) S2 isoform in cases. A similar but statistically insignificant tendency was seen in northern Europeans. In the three other regions, however, the distribution of apo(a) phenotypes among cases and controls was similar, and in the study population overall, the distribution of apo(a) phenotypes did not differ significantly (P = .74) between cases and control subjects.