Heart Disease In Middle-aged Men Research Articles

Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up

BackgroundIschaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied.PurposeTo investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age.Method“The Study of Men Born in 1943” is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups.ResultsOf 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model’s discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up.ConclusionIn this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population.Trial registration: The study is registered at Clinical Trials.gov Identifier number: NCT03138122

P4155Multiple modality biomarkers predict ischemic heart disease in middle-aged men from the general population during a 21-year follow-up

Abstract Background Ischemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. An early prediction of risk for IHD in a general population would be helpful for preventive decision-making. It is well known that biomarkers including troponine, natriuretic peptides and inflammatory biomarkers are useful prognostic predictors for IHD, their long-term predictive values in a general population for incident IHD have not been studied. Purpose The aim of the study was to investigate the predictive value of multi-modality biomarkers on the incident IHD in a random male sample from the general population followed from the age of 50 to 71 years. Method “The study of Men Born in 1943” is a longitudinal cohort study of men living in the city of Gothenburg in Sweden. All patients underwent a baseline examination in 1993, which included physical examination, questionnaires and blood samples. Because of multifactorial nature of atherosclerosis, a panel of biomarkers representing multiple mechanisms such as high-sensitivity troponine (hs-TNT), interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), urat, ferritin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed from blood samples collected at 50 years of age. Incident IHD was defined as new-onset one of following (myocardial infarction, hospitalized unstable angina and intervention with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during 1993–2014. The impact of biomarkers on incident IHD was studied using univariable, followed by stepwise and multivariable Cox proportional hazards models. Results Among the, 753 patients in the study, 105 patients (13,9%) developed IHD during 21 years of follow up with an event rate per 1000 person years 7.49 and a 95% confidence interval (CI) of 6.19 - 9.07. In Cox proportional hazards model for time to first occurrence of IHD, univariable analyses showed that multi-modality biomarker (CRP >1 mg/ml, NT-proBNP >100 pg/mL, troponin >10 ng/L, IL-6 >8 ng/L) provide most powerful prediction, followed by total cholesterol and fasting plasma glucose. In multivariable Cox proportional hazards model for time to first of IHD, above four-biomarker combination modality remains a most powerful predictor with risk increased by one additional biomarker [Hazard Ratio (95% CI): 1.69 (1.26 - 2.26), p=0.0004], followed by total cholesterol (mmol/L) with risk increased by one [Hazard Ratio (95% CI: 1.31 (1.09 - 1.56), p=0.0031], and fasting plasma glucose (mmol/L) with risk increased by one unit [Hazard Ratio (95% CI): 1.11 (1.01 - 1.22), p=0.038]. Conclusion A multi-modality biomarker strategy can be used to predict increased risk of developing IHD during the following two decades after 50 years, enabling us to identify individuals who might benefit from early intensive risk modification to prevent the development of IHD.

Severity of dental caries and risk of coronary heart disease in middle-aged men and women: a population-based cohort study of Korean adults, 2002\u20132013

We aimed to evaluate the risk of coronary heart disease (CHD) according to dental caries status in middle-aged patients using a population-based cohort database containing medical/dental claims, health examination, and death records in the Republic of Korea. A total of 234,597 patients were identified in the database who were without history of cardiovascular disease, including 104,638 patients without dental caries, 41,696 with incipient/moderate stage dental caries, and 88,262 advanced/severe dental caries. We used Cox proportional hazards model adjusted for sociodemographic, lifestyle, and medical characteristics to compute hazard ratio (HR) and 95% confidence intervals (95% CI) for CHD according to severity of dental caries. During 1,491,190 person-years of follow-up, there were a total of 6,015 CHD events. After adjustment for potential confounders, patients in the highest quartile of outpatient visits for advanced/severe stage dental caries was associated with an increase in CHD risk (HR = 1.13; 95% CI: 1.04–1.22) as compared with patients without dental caries. When the analysis was restricted to the patients with advanced/severe dental caries, dose-response relationship between number of outpatient visits for dental caries and risk of CHD was observed (Ptrend: <0.001). Prevention and control of dental caries might be worth promoting in clinical practice to prevent CHD.

Relevance of intermediate-density lipoprotein cholesterol to Framingham risk score of coronary heart disease in middle-aged men with increased non-HDL cholesterol

Cholesterol levels of non-high-density lipoprotein (non-HDL), which contains low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL) and chylomicron (CM) remnant, have been proven to perform a significant predictor of coronary heart disease (CHD) better than LDL-cholesterol regardless of triglyceride (TG) levels. The present study investigated the relevance of TG-rich lipoproteins (IDL, VLDL, CM) to Framingham risk score (FRS) predictive of 10-year CHD risk. Lipoprotein profiles (cholesterol levels of HDL, LDL, IDL, VLDL, CM) in Japanese men (n = 487) who underwent medical check-up were determined by using our developed anion-exchange high performance liquid chromatography (AEX-HPLC). Total-cholesterol (TC), TG, fasting blood sugar (FBS) and hemoglobin (Hb) A1c were measured by routine methods. The lipoprotein profiles, non-HDL-cholesterol, TC, and TG were examined on these associations with FRS. The lipid levels except for CM-cholesterol were significantly different between two groups (low FRS, < 10%; high FRS, ≥10%) (P < 0.0001), and body mass index (BMI), TC, TG, IDL-, and VLDL-cholesterol were significantly and positively correlated with FRS. Among them, the significant association of non-HDL-cholesterol to FRS was noted (r = 0.411, P < 0.0001). Multiple stepwise regression analysis shows that, in addition to non-HDL-cholesterol, IDL-cholesterol in TG-rich lipoproteins was significantly correlated with FRS in independently of BMI. These correlation results were similarly found even when the part of the study subjects (n = 348) without the drug therapy for hyperlipidemia, diabetes, and hypertension was investigated. These results suggest that IDL-cholesterol may serve as a useful marker for CHD risk in Japanese men with increased non-HDL-cholesterol.

Dietary protein and risk of ischemic heart disease in middle-aged men

Prospective studies in US women have suggested an inverse relation between dietary protein and risk of ischemic heart disease (IHD). However, no large-scale prospective studies have been conducted in US men. The objective was to examine the association between dietary protein and risk of IHD in a prospective study of US men. Intakes of protein and other nutrients were assessed by using a validated food-frequency questionnaire at 4 time points during follow-up of 43,960 men participating in the Health Professionals Follow-Up Study. Cox proportional hazards models were used to calculate multivariable-adjusted relative risks (RRs) and 95% CIs. During 18 y of follow-up, we documented 2959 incident cases of IHD. The RR of IHD was 1.08 (95% CI: 0.95, 1.23; P for trend = 0.30) comparing the top with the bottom quintile of percentage of energy from total protein. RRs for animal and vegetable protein were 1.11 (95% CI: 0.97, 1.28; P for trend = 0.18) and 0.93 (95% CI: 0.78, 1.12; P for trend = 0.49), respectively. When the population was restricted to "healthy" men (those free of hypertension, hypercholesterolemia, and diabetes at baseline), the RR of IHD was 1.21 (95% CI: 1.01, 1.44; P for trend = 0.02) for total protein, 1.25 (95% CI: 1.04, 1.51; P for trend = 0.02) for animal protein, and 0.93 (95% CI: 0.72, 1.19; P for trend = 0.65) for vegetable protein. We observed no association between dietary protein and risk of total IHD in this group of men aged 40-75 y. However, higher intake of animal protein may be associated with an increased risk of IHD in "healthy" men.

Vital Exhaustion as a Risk Factor for Adverse Cardiac Events (from the Atherosclerosis Risk In Communities [ARIC] Study)

Vital exhaustion, defined as excessive fatigue, feelings of demoralization, and increased irritability, has been identified as a risk factor for incident and recurrent cardiac events, but there are no population-based prospective studies of this association in US samples. We examined the predictive value of vital exhaustion for incident myocardial infarction or fatal coronary heart disease in middle-aged men and women in 4 US communities. Participants were 12,895 black or white men and women enrolled in the Atherosclerosis Risk In Communities (ARIC) study cohort and followed for the occurrence of cardiac morbidity and mortality from 1990 through 2002 (maximum follow-up 13.0 years). Vital exhaustion was assessed using the 21-item Maastricht Questionnaire and scores were partitioned into approximate quartiles for statistical analyses. High vital exhaustion (fourth quartile) predicted adverse cardiac events in age-, gender-, and race-center-adjusted analyses (1.69, 95% confidence interval 1.40 to 2.05) and in analyses further adjusted for educational level, body mass index, plasma low-density lipoprotein and high-density lipoprotein cholesterol levels, systolic and diastolic blood pressure levels, diabetes mellitus, cigarette smoking status, and pack-years of cigarette smoking (1.46, 95% confidence interval 1.20 to 1.79). Risk for adverse cardiac events increased monotonically from the first through the fourth quartile of vital exhaustion. Probabilities of adverse cardiac events over time were significantly higher in people with high vital exhaustion compared to those with low exhaustion (p = 0.002). In conclusion, vital exhaustion predicts long-term risk for adverse cardiac events in men and women, independent of established biomedical risk factors.

Alcohol use and cardiovascular health outcomes: a comparison across age and gender in the Winnipeg Health and Drinking Survey Cohort

research has reliably demonstrated cardioprotection from regular alcohol use. Heavy episodic drinking (HED), however, negates these beneficial effects and increases the risk of cardiovascular disease (CVD). The impact of age on the health effects of episodic drinking has not been evaluated. to examine the association between alcohol volume and pattern of consumption on the risk of cardiovascular morbidity and mortality across the lifespan. prospective, community-based cohort study of adults in Winnipeg, Manitoba, Canada. a total of 1,154 participants (580 men and 574 women) aged 18-64 surveyed at baseline (1990-91) on alcohol consumption levels and pattern of use. usual alcohol consumption was measured using a quantity-frequency approach. HED was estimated by asking participants how often they consumed eight or more drinks in one sitting in the past year. Questions were asked separately for wine, beer and spirits. Surveillance for cardiovascular events was conducted for 10 years (i.e. up to age 74 years). Diagnoses of CVD were obtained via health utilization records. Cox proportional hazard models were derived for both genders and for 'young adults' (baseline age 18-34), 'middle-aged adults' (baseline age 35-49) and 'older adults' (baseline 50-64). Models were adjusted for marital status, cigarette smoking status and educational level. Reduced risk of CVD was associated with usual consumption, whereas an increased risk was associated with HED. Among male usual drinkers, cardioprotection was afforded only to middle and older age groups. The benefits of regular consumption were seen only in the youngest age group among women. The heaviest usual consumption category was associated with a decreased risk of CVD in men. Heavy episodic drinking increased the risk of coronary heart disease in middle-aged men and was marginally significant in middle-aged women. Risk of hypertension was elevated in older men with heavy episodic drinking. The well-established relationship between regular alcohol consumption and decreased risk of CVD may not become evident until middle age or older in men. Women may benefit from usual consumption at a much younger age. In both sexes, however, these beneficial effects of alcohol use are negated when alcohol is consumed in a heavy episodic drinking pattern, particularly for middle-aged and older men.

Notes on interval estimation of risk difference in stratified noncompliance randomized trials: A Monte Carlo evaluation

When comparing an experimental treatment with a standard treatment in a randomized clinical trial (RCT), we often use the risk difference (RD) to measure the efficacy of an experimental treatment. In this paper, we have developed four asymptotic interval estimators for the RD in a stratified RCT with noncompliance. These include an asymptotic interval estimator based on the weighted-least-squares (WLS) estimator of the RD, an asymptotic interval estimator using tanh − 1 ( x ) transformation with the WLS optimal weight, an asymptotic interval estimator derived from Fieller’s Theorem, and an asymptotic interval estimator using a randomization-based approach. Based on Monte Carlo simulations, we have compared these four asymptotic interval estimators with the asymptotic interval estimator recently proposed elsewhere. We have found that when the probability of compliance is high, the interval estimator using a randomization-based approach is probably more accurate than the others, especially when the stratum size is not large. When the probability of compliance is moderate, the interval estimator using tanh − 1 ( x ) transformation is likely to be the best among all interval estimators considered here. We note that the interval estimator proposed elsewhere can be of use when the underlying RD is small, but lose accuracy when the RD is large. We also note that when the number of patients per assigned treatment is large, the four asymptotic interval estimators developed here are essentially equivalent; they are all appropriate for use. Finally, to illustrate the use of these interval estimators, we consider the data taken from a large field trial studying the effect of a multifactor intervention program on reducing the mortality of coronary heart disease in middle-aged men.

Hypertriglyceridemic waist: A useful screening phenotype in preventive cardiology?

The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Notes on Test Equality in Stratified Noncompliance Randomized Trials

In randomized clinical trials, we often encounter the situations in which there are some patients who do not comply with their assigned treatments and also some confounders that are needed to control in assessing a treatment effect. To account for both noncompliance and confounders, we developed four asymptotic test procedures: (1) the test procedures based on the risk difference (RD) using the intention-to-treat approach with the optimal weight derived by the weighted least squares method; (2) the test procedure based on the instrumental variable (IV) estimator for the RD with the corresponding weighted least squares optimal weight; (3) the test procedure based on the IV estimator for the RD with tamhr−1 (x) transformation; and (4) the test procedure based on the Mantel-Haenszel estimator for the RD using the intention-to-treat approach. We apply Monte Carlo simulation to evaluate the finite sample performance of these test procedures in a variety of situations. Except for the test procedure using tanhr−1 (x) transformation, all the other procedures can perform well with respect to type I error even when the mean stratum size is moderate. We further find that when the mean stratum size is moderate, the test procedure based on IV estimator directly is generally preferable to the others with respect to power subject to maintaining type I error less than or approximately equal to the nominal α-level. When both the probability of compliance and the mean stratum size are large, however, we find that the test procedure based on IV estimator with tanh−1 (x) transformation is more powerful than the others without losing the accuracy of type I error. Finally, we use the data taken from a field trial of studying the effect of a multifactor intervention program on the mortality incidence from coronary heart disease in middle-aged men to illustrate the practical use of these test procedures.

Invited commentary

Invited commentary

Application of U.S. guidelines in other countries: Aspirin for the primary prevention of cardiovascular events in Japan

Clinical guidelines developed in the United States are used frequently in other countries without assessment of their appropriateness in non-U.S. populations. We explored the relevance of recent U.S. guidelines for the use of aspirin for the primary prevention of cardiovascular events in the Japanese population. From a systematic search of published data, estimates were derived for rates of coronary heart disease, hemorrhagic stroke, and major gastrointestinal bleeding for the Japanese population and for subgroups with different risk factors. Odds ratios derived from meta-analyses were used to assess the potential benefits and risks of aspirin use. The estimated incidence of coronary heart disease in middle-aged men in Japan is lower than in the United States (1.57 vs. 6.0 per 1000 person-years), while that of hemorrhagic stroke is higher (1.14 vs. 0.37 per 1000 person-years). Because of higher baseline rates of hemorrhagic diseases, the expected reduction in cardiovascular events with aspirin use would be offset by a greater increase in hemorrhagic complications for women and most men in Japan, except for those with both hypertension and diabetes. To achieve the same 2:1 ratio of coronary heart disease events avoided to hemorrhagic events caused that is implied by the 3% threshold for 5-year coronary disease risk in U.S. guidelines, a 6% to 14% risk threshold, depending on patient age, seems appropriate for recommending aspirin in Japanese patients. The thresholds of antiplatelet therapy for Asian populations should be two to five times higher than those for the U.S. population because of higher risks of hemorrhagic complications. The assumptions and implications of U.S. guidelines should be evaluated before use in other countries.

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study.

Measuring C-reactive protein (CRP) has been recommended to identify patients at high risk for coronary heart disease (CHD) with low LDL cholesterol (LDL-C). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme associated primarily with LDL. In a prospective, case cohort study in 12 819 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities study, the relation between Lp-PLA2, CRP, traditional risk factors, and risk for CHD events over a period of approximately 6 years was examined in a proportional hazards model, stratified by LDL-C. Lp-PLA2 and CRP levels were higher in the 608 cases than the 740 noncases. Both Lp-PLA2 and CRP were associated with incident CHD after adjustment for age, sex, and race with a hazard ratio of 1.78 for the highest tertile of Lp-PLA2 and 2.53 for the highest category of CRP versus the lowest categories. Lp-PLA2 correlated positively with LDL-C (r=0.36) and negatively with HDL-C (r=-0.33) but not with CRP (r=-0.05). In a model adjusted for traditional risk factors including LDL-C, the association of Lp-PLA2 with CHD was attenuated and not statistically significant. For individuals with LDL-C below the median (130 mg/dL), Lp-PLA2 and CRP were both significantly and independently associated with CHD in fully adjusted models. For individuals with LDL-C <130 mg/dL, those with both Lp-PLA2 and CRP levels in the highest tertile were at the greatest risk for a CHD event. Lp-PLA2 and CRP may be complementary in identifying individuals at high CHD risk who have low LDL-C.

A twin study of depression symptoms, hypertension, and heart disease in middle-aged men.

Epidemiological and clinical studies have established an association between major depression and cardiovascular disease. We utilized a twin design to test whether there are common genetic and environmental risk factors underlying depression symptoms, hypertension and heart disease. Association studies were conducted with 6,903 male-male twins from the Vietnam Era Twin Registry who responded to both a 1990 health questionnaire and a 1992 telephone administration of a structured psychiatric interview. Data from 2,731 complete twin pairs were used to fit genetic models which determined the extent to which lifetime depression symptoms, heart disease and hypertension shared genetic and/or environmental factors. Heart disease was significantly associated with 1-4 symptoms and 5 or more symptoms of depression (odds ratio [OR] = 2.62; 95% confidence interval [CI]: 1.54-4.46 and OR = 4.02; 95% CI: 2.16-7.46). Hypertension was significantly associated with 1 to 4 symptoms and 5 or more symptoms of depression (OR = 1.29; 95% CI: 1.11-1.50 and OR = 1.49; 95% CI: 1.21-1.83). The genetic correlations were significant between depression symptoms and hypertension (r =.19), and between depression symptoms and heart disease (r =.42). Of the total variance in depression, 8% was common to hypertension and heart disease, 7% of the variance in hypertension was common with depression symptoms and heart disease, and 64% of the variance in heart disease was common with depression symptoms and hypertension. Men who reported cardiovascular disease were significantly more likely to have depression symptoms. The lifetime co-occurrence of these phenotypes is partly explained by common genetic risk factors.

Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a prospective study

The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are important determinants of plasma lipid concentrations, and the epsilon4 allele is associated with raised risk of coronary heart disease. We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype. We enrolled 3052 middle-aged men who were free of coronary heart disease for prospective cardiovascular surveillance in the second Northwick Park Heart Study (NPHSII). Smoking habit was ascertained at baseline and yearly by questionnaire. APOE genotype was identified by PCR and restriction enzyme digestion. Endpoints were fatal coronary heart disease, non-fatal myocardial infarction, and coronary artery surgery and silent myocardial infarction at follow-up. During 18836 person years of surveillance, 96 men had an acute myocardial infarction, 26 needed coronary artery surgery, and 14 had silent myocardial infarctions. Compared with never-smokers, risk of coronary heart disease in ex-smokers was 1.34 (95% CI 0.86-2.08) and in smokers it was 1.94 (1.25-3.01). This risk was independent of other classic risk factors. In never-smokers, risk was closely similar in men with different genotypes. Risk in men homozygous for the epsilon3 allele was 1.74 (1.10-2.77) in ex-smokers and 1.68 (1.01-2.83) in smokers, whereas in men carrying the epsilon4 allele risk was 0.84 (0.40-1.75) and 3.17 (1.82-5.50), respectively, with no significant differences in risk in the epsilon2 carriers. For the epsilon3 group, the genotype effect on risk was no longer significant after adjustment for classic risk factors (including plasma lipids). However, even after adjustment, smokers who were carriers of the epsilon4 allele, showed significantly raised risk of coronary heart disease compared with the non-smoking group (2.79, 1.59-4.91, epsilon4-smoking interaction p=0.007). Smoking increases the risk of coronary heart disease in men of all genotypes but particularly in men carrying the epsilon4 allele.

Finalists, The Jeremiah and Rose Stamler Research Award for New Investigators Fatty fish consumption and ischemic heart disease mortality in older adults: The Cardiovascular Health Study

P01 OBJECTIVE. To assess whether dietary intake of fatty fish is associated with a reduced risk of ischemic heart disease mortality in older adults. BACKGROUND. Dietary intake of fatty fish has been associated with a reduced risk of fatal ischemic heart disease in middle-aged men and women. This association, however, has not been specifically evaluated in older adults. METHODS. In 3968 men and women ≥ age 65 enrolled in the Cardiovascular Health Study and free of known cardiovascular disease at baseline, dietary intake of fish (fried fish, tuna fish, and other fish) was assessed through a detailed picture-sort food frequency questionnaire. In a subset of 348 persons, dietary intake of tuna and other fish combined (“fatty fish”) correlated with plasma phospholipid levels of combined docosahexaenoic acid (DHA, 22:6 n-3)) and eicosapentaenoic acid (EPA, 20:5 n-3) (r = 0.40, p &lt; 0.001); intake of fried fish did not correlate with plasma phospholipid levels of these long-chain n-3 fatty acids (r = 0.05, p = 0.37). Participants were prospectively followed for a mean period of 6.8 years for death from ischemic heart disease (incident fatal myocardial infarction [MI] plus coronary heart disease death) and nonfatal MI. FINDINGS. Compared to intake of less than one serving of fatty fish per week, intake of at least one serving of fatty fish per week was associated with a 35% lower risk of death from ischemic heart disease (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.45 to 0.94) but was not associated with a lower risk of nonfatal MI (HR 0.86; 95% CI 0.64 to 1.15), after adjustment for age, gender, diabetes, smoking status, education, and total caloric intake. CONCLUSIONS. These findings suggest that consumption of at least one serving of fatty fish per week is associated with a lower risk of death from ischemic heart disease in persons aged 65 years and older.

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.

An Association Between Plasma Free Protein S Concentration and Risk of Coronary Heart Disease in Middle-Aged Men

Protein S is a vitamin K-dependent protein with anticoagulant properties. Case series have reported reduced plasma concentrations in patients with arterial thromboses, while other studies have reported increased levels in patients with coronary heart disease (CHD). The present study sought to clarify the relation between free protein S and risk of CHD. A prospective survey was conducted of 3000 men aged 50 to 61 years, free of clinical CHD at baseline. Free protein S was measured by commercial immunoassay. End-points recorded were sudden coronary death, first nonfatal and fatal myocardial infarction (MI), surgical intervention for symptomatic, angiographically demonstrated CHD, and all-causes mortality. Statistical analysis employed univariate incidence rate ratios followed by Cox proportional hazards regression. There were 168 CHD events recorded during 21,000 person−years of risk. Mean free protein S concentration was 6% higher in those who developed CHD than in the remainder, the crude hazard ratio (HR) for a one standard deviation (S.D.) increase in free protein S being 1.25 (95% CI, 1.08–1.25). Free protein S was associated with cholesterol concentration and other conventional CHD risk factors. In multivariate regression analysis, after adjustment for conventional CHD risk factors a 1 S.D. increase in free protein S was associated with a HR of 1.15 (0.98–1.35) for CHD, of borderline conventional statistical significance. This association of free protein S with risk of CHD may reflect effects of plaque-destabilising inflammatory activity on protein S levels.

Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.