Disease In Middle-aged Men Research Articles

Heart disease in women

PREVIEWFor decades, coronary artery disease (CAD) was thought to be primarily a disease of middle-aged men, in whom most research was conducted. But CAD afflicts a diverse patient population, and a major subset of those patients—women—present special diagnostic and therapeutic challenges for the primary care physician. In this article, Dr Rosenfeld provides an overview of CAD in women and discusses its causes and risk factors, prevention strategies, and gender-specific characteristics. She also examines the effect of gender-biased research on the views of both patients and physicians.

Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.

Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls "nested" in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1. 90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori-seronegative individuals, the odds ratio for CHD was 1. 42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori-seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA-seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.

Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials.

Lowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women. To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women. Trials published in English-language journals were retrieved by searching MEDLINE (1966-December 1998), bibliographies, and authors' reference files. Studies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified). Information on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus. Data from the 5 trials, with 30 817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Stati n drug treatment was associated with a20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31 % in major coronary events (95% confidence interval [CI], 26%-36%) and 21 % in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% Cl, 13 %-42 %) and men (31 %; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31 %; 95% CI, 24%-36%). Our meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.

Low Dehydroepiandrosterone Sulfate and Heart Disease in Middle-Aged Men: Cross-Sectional Results from the Massachusetts Male Aging Study

PURPOSE: Serum concentrations of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS), both of which decline with age more markedly than other sex hormone levels, have been alternately credited and discredited as “protective” correlates of heart disease. Baseline data from the Massachusetts Male Aging Study (MMAS), collected in 1987–89, provided a large population-based random sample (n = 1709) in which to examine cross-sectionally the relation of DHEA and DHEAS levels to heart disease, while controlling for a comprehensive set of potential confounders including serum lipid and hormone levels as well as smoking, alcohol intake, obesity, hypertension, diabetes, diet, medication, physical activity, and psychological measures.METHODS: The subjects were men aged 40–70 years, randomly sampled from the Massachusetts state census listing, measured and interviewed at home. Nonfasting blood samples were assayed for hormones and lipids.RESULTS: In all strata of age, smoking, and alcohol intake, the age-adjusted odds ratio for self-reported heart disease was between 0.55 and 0.85 per standard deviation (SD) of log DHEA and DHEAS concentration. Multiple logistic regression analysis indicated a strong independent role for DHEAS as a predictor of self-reported heart disease, controlling for age and the potential confounders listed above. The multiply-adjusted odds ratio for heart disease was 0.64 per SD log DHEAS concentration, with 95% confidence interval (CI) 0.50–0.83 (P = 0.0002). The DHEAS effect was not diminished by controlling for use of cardiac, vasodilator, antihypertensive, or lipid-lowering medication.CONCLUSIONS: These findings suggest that serum DHEAS levels bear an inverse relationship to heart disease, independently of a large set of established cardiovascular risk factors. The cross-sectional nature of this study requires that the findings be interpreted with caution.

Effects of diet composition on coagulation pathways

Total dietary fat intake is an important determinant of factor VII coagulant activity, a hemostatic risk factor for fatal ischemic heart disease in middle-aged men. This association has a long-term effect by which a high-fat diet increases plasma factor VII antigen concentration, and an acute effect whereby a small proportion of factor VII is converted from its proenzyme to active serine protease for several hours postprandially. In adults whose usual diet is rich in long-chain saturated fatty acids, postprandial activation of factor VII occurs irrespective of the fatty acid composition. The underlying mechanism appears to require lipolysis and the presence of another coagulant protein, factor IX. There is limited evidence that factor VII activation after a meal rich in polyunsaturated fatty acid is blunted when the background diet also has a high content of polyunsaturated fatty acid. Meals rich in medium-chain triacylglycerols do not induce factor VII activation. The effects of dietary enrichment with n-3 fatty acids on factor VII are uncertain. All studies have been confined to the fasting state, and only one suggested changes consistent with factor VII activation. Fibrinogen concentration, another major hemostatic risk factor for ischemic heart disease, is uninfluenced by dietary fat content or composition, the one exception being inconsistent reports of a reduction after dietary enrichment with n-3 fatty acids. Overall, the evidence so far indicates that total dietary fat intake is more important than dietary fat composition for factor VII and by implication its attendant risk of fatal ischemic heart disease in high-risk populations.

Cohort study of ethnic group and cardiovascular and total mortality over 15 years

Altogether, 3365 men and 3266 women who attended two cardiovascular screenings in 1974–1975 and 1977–1978, have been followed with respect to death for an average of 15 years. The mortality from coronary heart disease was lower in men who reported being of Lappish origin than in men who reported Norse origin at both screenings (Rate ratio: 0.38 [0.20–0.71]), when other major risk factors were taken into account. Among men without history of cardiovascular disease or symptoms of angina pectoris the rate ratio became 0.24 (0.09–0.63). With cardiovascular death as the endpoint, the corresponding rate ratios were 0.42 (0.25–0.73) and 0.31 (0.15–0.67). In women, a non-significant lower mortality was seen in the Lappish group than in the Norse group. This study is suggestive of some protection from coronary heart disease in middle-aged men of Lappish origin.

Smoking habits and risk of fatal stroke: 18 years follow up of the Oslo Study.

To examine the risk of fatal stroke in relation to smoking habits in men screened for the Oslo study. The Oslo study is a prospective, cohort study of the epidemiology and preventive aspects of cardiovascular diseases in middle aged men. Screening started in May 1972 and results after 18 years of follow up are reported. There were 16209 men aged 40-49 years, of whom 16173 had no stroke history. Eighty five men died from stroke, of whom 48 were daily cigarettes smokers, 7 were pipe and cigar smokers, 15 smoked cigarettes and pipe or cigars daily, 11 were previous cigarette smokers, and 4 had never smoked cigarettes. Results of proportional hazards regression analysis adjusted for age, diastolic blood pressure, and glucose concentration showed the following rate ratios (RR) (95% confidence interval) of smoking groups compared with those who had never smoked or had previously smoked: combined cigarette and cigar or pipe smokers, RR = 6.1 (3.0, 12.5); cigarettes only, RR = 4.1 (2.3,7.4); and pipe and/or cigars only RR = 2.2 (0.9,5.5). The overall, age adjusted risk of smoking cigarettes daily was 3.5 and was found to increase with increasing cigarette consumption. Regardless of their smoking group, stroke cases had increased diastolic (DBP) and systolic blood pressure (SBP) when compared with men who had not had a stroke. The absolute differences in DBP and SBP between stroke cases and others for never and previous cigarette smokers versus daily smokers were twice as large: DBP, 12.1 mmHg versus 6.5 mmHg respectively and SBP, 16.0 mmHg versus 7.1 mmHg respectively. A high BMI increased the risk of fatal stroke of never and previous cigarette smokers. Men being treated for hypertension at the time of screening had three times the crude risk of fatal stroke of men who were not taking hypertensive treatment. Daily cigarette smoking increased the risk of fatal stroke three and a half times. Combined cigarette and pipe or cigar smoking had a higher risk than smoking cigarettes only. An increased risk was found in relation to increased daily cigarette consumption.

Influence of fathers' social class on cardiovascular disease in middle-aged men

The independent effect of early life circumstances on adult cardiovascular risk is still unresolved. We assessed the associations of father's social class with cardiovascular risk factors and with risk of ischaemic heart disease and stroke in adult life. We did a longitudinal study of cardiovascular disease in 5934 men aged 40-59 years at enrollment. A cross-sectional measurement survey was done between 1978 and 1980 and a follow-up questionnaire was completed in 1992. The main endpoints were non-fatal myocardial infarction and stroke based on general practitioners' reports obtained between screening and 1992 and on recall of physician-diagnosed ischaemic heart disease in the 1992 questionnaire. Father's social class was strongly associated with social class in adulthood (fathers' occupation was manual for 41.3% of professionals [I] vs 89.1% for unskilled manual workers [V]) and was significantly related to height (non-manual vs manual 175.4 cm [SE 0.2] vs 172.9 cm [0.1], p < 0.0001) and obesity (213 [14.1%] vs 804 [20.1%], p < 0.0001) irrespective of adult social class; no association was found with blood glucose (log, 1.69 [0.005] vs 1.70 [0.003], p = 0.22) or cholesterol (6.34 [0.03] vs 6.29 mmol/L [0.02], p = 0.16. Men whose fathers' social class was manual had significantly higher rates of non-fatal myocardial infarction (342/4006 vs 92/1510) and self-reported physician-diagnosed ischaemic heart disease (686/4006 vs 192/1510) than men whose fathers' social class was non-manual, even after adjustment for adult social class and other established risk factors (relative odds 1.3 [95% Cl 1.0-1.7], p < 0.05 and 1.3 [1.1-1.6], p < 0.01, respectively). The influence of father's social class on non-fatal myocardial infarction and ischaemic heart disease was only seen in men whose adult social class was non-manual. No association was seen between father's social class and non-fatal stroke. Father's social class is strongly associated with adult social class. The higher risk of non-fatal myocardial infarction and self-reported physician-diagnosed ischaemic heart disease seen in men whose father's social class was manual suggests that socioeconomic status early in life has some persisting influence on ischaemic heart disease risk in adult life.

Autres pays, autres coeurs? Dietary patterns, risk factors and ischaemic heart disease in Belfast and Toulouse

The WHO MONICA project monitors trends and determinants in cardiovascular disease to relate classical risk factor changes to trends in incidence rates. The Belfast and Toulouse MONICA centres have also collaborated in dietary studies. Both centres have validated incidence and attack rates for ischaemic heart disease using coronary event registration. These data confirm that the disease in middle-aged men is between three and four times as common in Belfast as in Toulouse. Risk factor surveys show some differences between the centres, but the overall risks assessed by two multiple logistic function scoring systems were identical. A weighed dietary survey revealed no important difference in macronutrient intake, although carbohydrate and saturated fat intake in Belfast was significantly higher. Protein, dietary cholesterol and polyunsaturated fat, particularly linoleic acid intake, was significantly higher in Toulouse, as was consumption of wine, cheese, fruit and vegetables, but not potatoes. The Northern Irish diet is typically Northern European, but although the diet in Toulouse has some features of the Mediterranean diet, it is not appreciably different from that in Belfast in terms of total fat intake. Major differences are present for several food items, and in general these differences add support to the antioxidant hypothesis.

Lifestyle and Biologic Factors Associated With Atherosclerotic Disease in Middle-aged Men

To examine the association between a variety of baseline lifestyle and biologic factors in a middle-aged cohort of Japanese-American men and the 20-year incidence rates of total atherosclerotic end points and each of the initial clinical manifestations of this disease, including fatal and nonfatal coronary heart disease, angina pectoris, thromboembolic strokes, and aortic aneurysms. Prospective epidemiologic study. Japanese-American men (N = 2710) between the ages of 55 and 64 years at the time of the initial clinical examination of the Honolulu Heart Program (1965 through 1968) free from evidence of coronary heart disease, cerebrovascular disease, cancer, or aortic aneurysms. Among the men studied, 602 atherosclerotic events developed during the 23-year period of follow-up (1965 through 1988). After adjustment for each of the baseline characteristics examined, significant positive associations between quartile cutoffs of body mass index, systolic blood pressure, serum levels of cholesterol, triglycerides, glucose, and uric acid, as well as cigarette smoking, and the occurrence of any atherosclerotic end point were seen, while an inverse association with alcohol consumption was observed. Characteristics associated with the development of other fatal and nonfatal clinical events in this cohort, including coronary heart disease, thromboembolic stroke, and aortic aneurysms are presented with accompanying relative and attributable risks. The results of this prospective epidemiologic study provide insights to the long-term predictive utility of the commonly accepted risk factors for coronary heart disease in relation to the different clinical manifestations of atherosclerosis in a middle-aged male cohort followed up for approximately 20 years. These results provide additional support for risk factor modification in middle-aged men and for the encouragement of positive long-term lifestyle changes.

Lifestyle and biologic factors associated with atherosclerotic disease in middle-aged men. 20-year findings from the Honolulu Heart Program

Lifestyle and biologic factors associated with atherosclerotic disease in middle-aged men. 20-year findings from the Honolulu Heart Program

The insulin resistance syndrome in smokers is related to smoking habits.

The relationship between smoking habits, insulin resistance, and related risk factors for cardiovascular disease was examined in 57 middle-aged male smokers whose degree of insulin resistance was quantified by using the euglycemic clamp technique. Smoking habits correlated with degree of insulin resistance and consequently with various manifestations of the insulin resistance syndrome including levels of insulin, high-density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 (PAI-1) activity. Smoking habits, independent of degree of insulin resistance, were also related to levels of total cholesterol and low-density lipoprotein cholesterol as well as triglycerides. Stepwise regression analyses considering the effects of age, lean body mass, body fat, body mass index, waist/hip ratio, and alcohol consumption showed that only smoking habits and percent body fat were independently related to degree of insulin resistance. This study shows that insulin resistance and the insulin resistance syndrome are important but not unique contributors to the strong risk profile for cardiovascular disease in middle-aged men who smoke.

Association between lipoprotein(a) and progression of coronary artery disease in middle-aged men

The association between lipoprotein(a) (Lp[a)) and progression of coronary artery disease (CAD) compared with other serum lipids was evaluated in 104 patients with angiographically proven coronary atherosclerosis. Patients were randomized to either an intervention or a control group. The 12-month intervention program consisted of a low-fat diet and daily physical exercise. Patients in the control group received “usual care” by their private physician. Eightyrthree patients (36 in the intervention and 47 in the control group) underwent repeat angiography after 1 year. Angiographically documented net regression was seen in 13 patients (8 in the intervention and 5 in the control group), no change was seen in 40 patients (21 in the intervention and 19 in the control group) and progression was noted in 30 patients (7 in the intervention and 23 in the control group). No correlation could be shown between Lp(a) and angiographically documented progression of the disease. In a multivariate analysis including metabolic variables, group assignment, age and smoking habits, only assignment to the intervention group (p = 0.0075) and a decrease in total cholesterol (p = 0.0167) were independently associated with the course of the disease. Patients with or without previous myocardial infarction (70 vs 34) did not differ in Lp(a) levels (median 9.15 vs 14.25 mg/dl). Patients with Lp(a) >25 mg/dl were younger than patients with Lp(a) ≤25 mg/dl (52 vs 55 years; p <0.03), indicating a connection between Lp(a) and the development of premature CAD. It is concluded that Lp(a) levels in middle-aged Caucasian men with CAD but without prominent primary or secondary hyperlipidemia due to other than alimentary causes have no association with progression of the disease, even though high Lp(a) levels might have contributed to the early development of the disease.

Environmental influences on hemostasis and thrombosis. Diet and smoking.

High levels of factor VII coagulant activity (VIIc) and fibrinogen concentration are independently associated with an increased risk of acute coronary heart disease in middle-aged men. Studies have, therefore, been undertaken to determine the responsiveness of these hemostatic factors to changes in diet and smoking habit. Plasma VIIc increases acutely with an increase in total fat intake, but fibrinogen is unaffected. In the general community, men who have a high total fat intake for their body size tend to have a high VIIc level. Changes in the dietary ratio of saturated to polyunsaturated fat of up to 14 days' duration have no effect on factor VIIc or fibrinogen (there are conflicting reports on the influence of dietary very-long-chain polyunsaturated fatty acids on fibrinogen concentration). Cigarette smokers have a higher fibrinogen concentration than do nonsmokers, but their levels slowly revert toward those of nonsmokers when the habit is relinquished.

Association between Plasma Lipoprotein Subclasses and the Course of Angiographically Defined Coronary Artery Disease in Middle-Aged Men

Association between Plasma Lipoprotein Subclasses and the Course of Angiographically Defined Coronary Artery Disease in Middle-Aged Men

Vascular reactivity in young adults and cardiovascular disease. A prospective study.

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.

Long-term mortality after a cardiovascular risk reduction program

Source Citation Strandberg TE, Salomaa VV, Naukkarinen VA, et al. Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men. JAMA. 1991 Sep 4;...

Self-perceived psychological stress and incidence of coronary artery disease in middle-aged men

Self-perceived psychological stress as a risk factor for coronary artery disease (CAD) was evaluated in a general population study comprising 6,935 men aged 47 to 55 years at baseline without previous myocardial infarction. In 1970 to 1973, the men answered a question about psychological stress defined as a feeling of tension, irritability or anxiety, or as having sleeping difficulties as a result of conditions at work or at home. Psychological stress was graded as follows: (1) never experienced stress; (2) ≥1 period of stress; (3) ≥1 period of stress during the last 5 years; (4) several periods of stress during the last 5 years; and (5 to 6) permanent stress during the last year or the last 5 years. After a mean follow-up of 11.8 years, 6% of the men with the lowest 4 stress ratings (n = 5,865) had either developed a nonfatal myocardial infarction or died from CAD, with no increase in risk from grade 1 to 4. The corresponding figure among the men with the highest 2 stress ratings (n = 1,070) was 10%; the odds ratio was 1.5 (95% confidence interval 1.2–1.9) after controlling for age and other risk factors. Similar, independent associations were seen with stroke, and with death from cardiovascular disease and from all causes, but not with death from cancer. With respect to CAD, no decrease in the effect of stress at baseline could be seen over time. No relation between life events and self-perceived psychological stress was found in another sample of 732 fifty-year-old men.

Long-term Mortality After 5-Year Multifactorial Primary Prevention of Cardiovascular Diseases in Middle-aged Men

To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases (CVD). The 5-year randomized, controlled trial was performed between 1974 and 1980. The subjects and their risk factors were reevaluated in 1985. Posttrial mortality follow-up was continued up to December 31, 1989. Institute of Occupational Health, Helsinki, Finland, and Second Department of Medicine, University of Helsinki. In all, 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s. In 1974, 1222 of these men who were clinically healthy, but with CVD risk factors, were entered into the primary prevention trial; 612 were randomized to an intervention and 610 to a control group. During the 5-year trial, the subjects of the intervention group visited the investigators every fourth month. They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly beta-blockers and/or diuretics) drugs. The control group was not treated by the investigators. Total mortality, cardiac mortality, mortality due to other causes. Total coronary heart disease risk was reduced by 46% in the intervention group as compared with the control group at end-trial. During 5 posttrial years, the risk factor and medication differences were largely leveled off between the groups. Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [CI], 1.01 to 2.08; P = .048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% CI, 1.31 to 4.46; P = .001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% CI, 0.31 to 1.22; P = .15), and 13 and one deaths due to violence (RR, 13.0; 95% CI, 1.70 to 98.7; P = .002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality. These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s) of methods used in the primary prevention of cardiovascular diseases.

Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men

Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men