Prognostic importance of presenting symptoms in patients undergoing exercise testing for evaluation of known or suspected coronary disease

PURPOSE: Chest symptoms, along with standard cardiovascular risk factors, are commonly factored into pretest risk stratification of patients who are referred for stress testing. We sought to determine the independent prognostic value of chest symptoms. METHODS: We studied the outcomes of 10,870 patients referred for symptom-limited exercise testing who had no history of myocardial revascularization, heart failure, or arrhythmias. Chest symptoms were prospectively characterized according to prespecified definitions. Propensity analysis was used to account for differences in baseline and exercise characteristics. RESULTS: Typical angina was present in 635 patients (6%), atypical angina in 3408 (33%), nonanginal chest pain in 1805 (17%), and dyspnea in 841 (8%). The remaining 4181 patients (38%) were asymptomatic. During a mean follow-up of 4.3 years, there were 381 deaths. After propensity matching patients who had typical angina with asymptomatic patients, symptoms were not predictive of mortality (adjusted hazard ratio [HR] = 0.8; 95% confidence interval [CI]: 0.6 to 1.3; P = 0.4). Among patients who had chest pain, typical angina was associated with a highly significant risk of mortality as compared with nonanginal chest pain (HR = 2.7; 95% CI: 1.4 to 5.1; P = 0.002), but not compared with atypical angina (HR = 1.3; 95% CI: 0.9 to 2.1; P = 0.21). CONCLUSION: After accounting for baseline and exercise characteristics, the presence of symptoms was not independently associated with increased mortality among patients undergoing testing for known or suspected coronary disease. Among patients who actually had chest pain, typical angina carried a higher mortality risk.     

Male pattern baldness and coronary heart disease: the Physicians' Health Study

OBJECTIVE: To examine the association between male pattern baldness and the risk of coronary heart disease (CHD) events. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study among 22,071 US male physicians aged 40 to 84 years enrolled in the Physicians' Health Study. Of these, 19,112 were free of CHD at baseline and completed a questionnaire at the 11-year follow-up concerning their pattern of hair loss at age 45 years. Response options included no hair loss, frontal baldness only, or frontal baldness with mild, moderate, or severe vertex baldness. MAIN OUTCOME MEASURES: Coronary heart disease events defined as nonfatal myocardial infarction (MI), angina pectoris, and/or coronary revascularization. RESULTS: During 11 years of follow-up, we documented 1446 CHD events in this cohort. Compared with men with no hair loss, those with frontal baldness had an age-adjusted relative risk (RR) of CHD of 1.09 (95% confidence interval [CI], 0.94-1.25), while those with mild, moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59), and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, <.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12). CONCLUSION: Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels.     

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study

OBJECTIVE: To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. METHODS: We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. RESULTS: During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. CONCLUSION: Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.     

Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study

The association of an elevated level of lipoprotein (a) (Lp(a)) with the development of coronary heart disease (CHD) remains controversial. Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. In addition, its possible interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.     

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men.

OBJECTIVES: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.     

Ankle brachial pressure index usefulness as predictor factor for coronary heart disease in diabetic patients

Ankle brachial pressure index (ABPI) is a non-invasive marker of atherosclerosis, helpful to identify subjects at high-risk for coronary heart disease (CHD) among large populations with cardiovascular disease (CVD) risk factors. The diagnostic role of ABPI has been also recognized in patients with diabetes. In the present study, the role of an ABPI score < 0.90 in predicting CHD has been evaluated in a large series of patients with Type 2 diabetes mellitus and compared to other known CVD risk factors. Nine hundred and sixty-nine (mean age was 66.1 yr) consecutive patients with Type 2 diabetes mellitus were evaluated. The patients were followed-up for 18.3+/-5.2 months (range 12- 24) and all events of CHD, defined as myocardial infarction, unstable and resting angina or coronary atherosclerosis at the instrumental investigation (at the coronary angiography and/or perfusion stress testing) were recorded. A rate of 17.5% of CHD events were recorded in diabetic population during the follow-up period. The relative risk of CHD was significantly increased for male patients [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.1-2.2], patients with age > or = 66 yr (OR: 1.8; 95% CI: 1.3-2.5), body mass index (BMI) > 30 (OR: 1.5; 95% CI: 1.1-2.1), waist circumference > 88 cm for females and 102 cm for males (OR: 1.5; 95% CI: 1.0-2.1), proteinuria > or = 30 microg per min (OR: 1.6; 95% CI: 1.1-2.3), LDL-cholesterol > or = 100 mg/dl (OR: 2.1; 95% CI: 1.5-3.0), glycated hemoglobin > 7% (OR: 1.6; 95% CI: 1.1-2.3), insulin therapy (OR: 1.9; 95% CI: 1.3-2.9), and ABPI < 0.90 (OR: 3.7; 95% CI: 2.2- 6.2). BMI was higher in patients with ABPI < 0.90 than in those with ABPI > or = 0.90 (p<0.05). At the multivariate analysis, ABPI < 0.90 was the best factor independently associated with CHD (p<0.001). APBI < 0.90 is strongly associated to CHD in Type 2 diabetic patients. We recommend to use ABPI in diabetic patients and to carefully monitor diabetic subjects with an ABPI lower than 0.90.     

Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors.

OBJECTIVES: To compare the significance of a specific feature of coronary atherosclerosis--coronary calcium--in asymptomatic black and white subjects with coronary risk factors. BACKGROUND: The natural history and clinical evolution of coronary atherosclerosis differs between blacks and whites. Differences in the underlying pathobiology of atherosclerosis may be one determinant of the ethnic variability in the clinical manifestation of coronary atherosclerosis. METHODS: In 1,375 high-risk but asymptomatic subjects (93 blacks [6.8%] and 1,282 whites [93.2%]) with at least one risk factor but no prior evidence of coronary disease, we assessed coronary risk factors, calculated Framingham risk of a coronary event and evaluated coronary calcium with digital subtraction fluoroscopy. We then followed these subjects clinically for 70 +/- 13 months, noting the occurrence of the following coronary events: death due to coronary heart disease (CHD); myocardial infarction (MI); angina pectoris; and performance of coronary bypass or angioplasty. RESULTS: Risk factor profiles were similar in black and white subjects (6-year Framingham risk 15 +/- 7% in blacks, 14 +/- 8% in whites [NS]). Coronary calcium was present in 59.9% of white subjects but only 35.5% of black subjects (p = 0.0001). Nevertheless, after 70 months of follow-up, more blacks than whites (22 blacks [23.7%] vs. 190 whites [14.8%]; p = 0.04) suffered one of the following end points: CHD death, MI, angina or revascularization. The age, gender and coronary risk-adjusted odds ratio of black race for at least one event was 2.16 (95% CI 1.34 to 3.48). CONCLUSIONS: Despite having a lowered prevalence of coronary calcium than high risk whites, high risk blacks suffer more CHD events. Coronary calcium therefore does not carry the same pathobiologic significance in blacks that it does in whites, consistent with the concept that there are specific racial differences in the natural history of CHD and its evolution into clinically manifest events.     

Impact of impaired fasting glucose on cardiovascular disease: the Framingham Heart Study.

OBJECTIVES: We sought to determine whether impaired fasting glucose (IFG) predicts cardiovascular disease (CVD) events. BACKGROUND: It is unclear which glucose threshold should define prediabetes. We compared the 1997 and 2003 American Diabetes Association (ADA) definitions of IFG to predict CVD. METHODS: Framingham offspring participants free of CVD, categorized by the 1997 ADA IFG definition (fasting plasma glucose 110 to 125 mg/dl; 6.1 to 6.9 mmol/l) or the 2003 definition (100 to 125 mg/dl; 5.6 to 6.9 mmol/l), were followed from 1983 to 2004. Pooled logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) for incident coronary heart disease (CHD; 291 events) or CVD (423 events). RESULTS: Four-year CHD event rates among women were 1.3% (100 to 109 mg/dl), 2.3% (110 to 125 mg/dl), and 2.9% (diabetes); whereas corresponding rates in men were 2.9%, 3.0%, and 8.7%. For the 2003 IFG definition, the OR for CHD among women was 1.7 (95% confidence interval [CI] 1.0 to 3.0, p = 0.048), whereas for the 1997 IFG definition, the OR for CHD in women was 2.2 (95% CI 1.1 to 4.4, p = 0.02), which was almost as high as for women with diabetes (OR 2.5, 95% CI 1.2 to 5.2, p = 0.01). For CVD, only the 1997 IFG definition yielded significantly greater odds of CVD in women (OR 2.1, 95% CI 1.2 to 3.6, p = 0.01). Men were not at increased odds of developing CVD or CHD by either definition. CONCLUSIONS: In women, both IFG definitions were associated with increased CHD risk, whereas neither IFG definition identified men at increased short-term risk for CHD or CVD. The finding that women with FPG 110 to 125 mg/dl had similar CHD risk compared with women with diabetes suggests that CHD risk in women may be elevated at a lower glucose level than for men.     

Serum parathyroid hormone levels predict coronary heart disease: the Troms? Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with hypertension, coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate serum parathyroid hormone (PTH) levels as an independent risk factor for coronary heart disease (CHD) in subjects with serum calcium within the reference range. DESIGN: Population-based cross-sectional study. METHODS: The Troms? Study was attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570 subjects. They all completed a questionnaire on medical history, including questions on angina pectoris and myocardial infarction along with a food-frequency questionnaire. A total of 1459 men and 1753 women with serum calcium 2.20-2.60 mmol/l, serum creatinine<121 micromol/l and who did not use diuretics were included in the present study. Linear regression was used to reveal associations between PTH, age, body mass index, serum calcium, calcium intake, cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status. A logistic regression model was used to find the independent predictors of CHD. RESULTS: When stratified for age the rate of CHD was higher in the subjects with serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95% CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30 pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90 pmol/l for men and <1.80 pmol/l for women). CONCLUSIONS: Serum PTH predicts CHD in subjects with calcium levels within the reference range. This may indicate a role for PTH in the development of CHD.     

A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study.

BACKGROUND--Although dietary factors are suspected to be important determinants of coronary heart disease (CHD) risk, the direct evidence is relatively sparse. METHODS--The Adventist Health Study is a prospective cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists. Extensive dietary information was obtained at baseline, along with the values of traditional coronary risk factors. These were related to risk of definite fatal CHD or definite nonfatal myocardial infarction. RESULTS--Subjects who consumed nuts frequently (more than four times per week) experienced substantially fewer definite fatal CHD events (relative risk, 0.52; 95% confidence interval [CI], 0.36 to 0.76) and definite nonfatal myocardial infarctions (relative risk, 0.49; 95% CI, 0.28 to 0.85), when compared with those who consumed nuts less than once per week. These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population. Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infarction (relative risk, 0.56; 95% CI, 0.35 to 0.89) and definite fatal CHD (relative risk, 0.89; 95% CI, 0.60 to 1.33) when compared with those who usually ate white bread. Men who ate beef at least three times each week had a higher risk of definite fatal CHD (relative risk, 2.31; 95% CI, 1.11 to 4.78), but this effect was not seen in women or for the nonfatal myocardial infarction end point. CONCLUSION--Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events. The favorable fatty acid profile of many nuts is one possible explanation for such an effect.     

Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population‐based cohort study

Objective

To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age‐ and sex‐matched non‐RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors.

Methods

We assembled a population‐based incidence cohort of 603 Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age‐ and sex‐matched non‐RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors.

Results

During the 2‐year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16–8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29–26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34–0.99) compared with non‐RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13–4.03) and sudden deaths (HR 1.94, 95% CI 1.06–3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16–0.80) compared with non‐RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates.

Conclusion

Patients with RA have a significantly higher risk of CHD when compared with non‐RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria–based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.

     

Antithrombotic treatment and the incidence of angina pectoris

BACKGROUND: In primary prevention, anticoagulation with warfarin sodium to an international normalized ratio of 1.5 and 75 mg of aspirin per day each reduced the incidence of coronary heart disease (CHD). Effects on the development of angina pectoris and total CHD (resulting from angina, myocardial infarction, and coronary death) have been assessed, particularly in light of recent evidence that warfarin may have a "durable effect" on CHD through effects on the pathologic condition of the vessel walls involved. METHODS: The Thrombosis Prevention Trial was carried out in 5499 men aged 45 through 69 years who were at increased risk of CHD. The trial was factorial, with 1 group taking active warfarin and active aspirin, 1 taking active warfarin and placebo aspirin, 1 taking placebo warfarin and active aspirin, and 1 taking double placebo treatment. In addition to those with myocardial infarction and coronary death, men developing angina pectoris after entry to the trial were identified. RESULTS: Warfarin appeared to reduce the incidence of stable angina by 16% (95% confidence interval [CI], -14 to 38), although not significantly (P =.26), while aspirin increased the incidence by 39% (95% CI, 0 to 91) (P =.05). The incidence of stable angina was 37% (95% CI, -1 to 60) less in those taking warfarin than in those taking aspirin (P =.05). Warfarin reduced total CHD by 18% (95% CI, 4 to 30) (P =.01), while the reduction due to aspirin was 8% (95% CI, -10 to 22) (P =.36). CONCLUSIONS: The results are compatible with the concept of a durable effect of warfarin on the chronic pathologic conditions underlying angina, although this has not been established with certainty. Further research is needed to confirm or refute our findings, because they carry potentially important implications for the primary prevention of CHD with the use of antithrombotic agents.     

Fibrinogen, angina and coronary heart disease in a Chinese population

Although fibrinogen is an established risk factor of coronary heart disease (CHD), whether fibrinogen is associated with CHD in Chinese is not clear. This population-based cross-sectional study aimed to analyse this relationship in Hong Kong Chinese. Fibrinogen was measured by the Clauss method in 1348 men and 1385 women aged 25-74 years. Severity of CHD was defined as most serious if the subjects had medically diagnosed CHD, as less serious if they had angina only, and as normal if they had neither. The prevalence of angina and CHD was respectively 2.4% and 2.2% in men and 3.2% and 2.7% in women. In men the age-adjusted mean fibrinogen concentration was 2.47 (95% confidence interval (CI) 2.43-2.51) g/l in the normal group, 2.65 (95% CI 2.45-2.85) g/l in the angina group, and 2.78 (95% CI 2.56-3. 00) g/l in the CHD cases (P<0.01); in women it was respectively 2.61 (95% CI 2.59-2.63), 2.66 (95% CI 2.50-2.82), 2.90 (95% CI 2.72-3.08) g/l (P<0.01). The differences were significant after adjustment of other significant risk factors. We conclude that fibrinogen should be considered as a risk factor in Chinese.     

Disability and Incident Coronary Heart Disease in Older Community‐Dwelling Adults: The Three‐City Study

OBJECTIVES: To prospectively assess the association between disability and incident fatal and nonfatal coronary heart disease (CHD) in older adults free of cardiovascular disease (CVD). DESIGN: A French multicenter prospective population‐based cohort of 9,294 subjects, aged 65 and older at baseline, recruited between 1999 and 2001 and followed for 6 years. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: Seven thousand three hundred fifty‐four participants with no history of CVD and with available information on disability status. Subjects were categorized at baseline as having no disability, mild disability (mobility only), and moderate or severe disability (mobility plus activities of daily living or instrumental activities of daily living). MEASUREMENTS: Incident fatal and nonfatal coronary events (angina pectoris, myocardial infarction, revascularization procedures, and CHD death). RESULTS: At baseline, the mean level of the risk factors increased gradually with the severity of disability. After a median follow‐up of 5.2 years, 264 first coronary events, including 55 fatal events, occurred. After adjustment for cardiovascular risk factors, participants with moderate or severe disability had a 1.7 times (95% confidence interval (CI)=1.0–2.7) greater risk of overall CHD than nondisabled subjects, whereas those with mild disability were not at greater CHD risk. An association was also found with fatal CHD, for which the risk increased gradually with the severity of disability (hazard ratio (HR)_{mild disability}=1.7, 95% CI=0.8–3.6; HR_{moderate/severe disability}=3.5, 95% CI=1.3–9.3; P for trend=.01). CONCLUSION: In older community‐dwelling adults, the association between disability and incident CHD is mostly due to an association with fatal CHD.     

Is the prevalence of coronary heart disease falling in British men?

OBJECTIVE—To assess whether long term trends over time in acute coronary heart disease (CHD) event rates have influenced the burden of prevalent CHD in British men.
DESIGN—Longitudinal cohort study.
PARTICIPANTS—7735 men, aged 40-59 at entry (1978-80), selected from 24 British towns.
METHODS—The prevalences of current angina symptoms and history of diagnosed CHD were ascertained by questionnaire in 1978-80, 1983-85, 1992, and 1996. New major CHD events (fatal and non-fatal) were ascertained throughout the study from National Health Service central registers and general practice record reviews. Age adjusted trends in CHD prevalence were compared with trends in major CHD event rates.
RESULTS—From 1978-1996 there was a clear decline in the prevalence of current angina symptoms: the age adjusted annual percentage change in odds was -1.8% (95% confidence interval (CI) -2.8% to -0.8%). However, there was no evidence of a trend in the prevalence of history of diagnosed CHD (annual change in odds 0.1%, 95% CI -1.0% to 1.2%). Over the same period, the CHD mortality rate fell substantially (annual change -4.1%, 95% CI -6.5% to -1.6%); rates of non-fatal myocardial infarction, all major CHD events, and first major CHD event fell by -1.7% (95% CI -3.9% to 0.5%), -2.5% (95% CI -4.1% to -0.8%), and -2.4% (95% CI% -4.3 to -0.4%), respectively.
CONCLUSIONS—These results suggest that middle aged British men are less likely to experience symptoms of angina than in previous decades but are just as likely to have a history of diagnosed CHD. Despite falling rates of new major events and falling symptom prevalence, the need for secondary prevention among middle aged men with established CHD is as great as ever.


Keywords: coronary heart disease; angina; prevalence; trends     

Soluble intercellular adhesion molecule-1 and long-term risk of acute coronary events in patients with chronic coronary heart disease. Data from the Bezafibrate Infarction Prevention (BIP) Study

OBJECTIVES: The goal of this study was to assess soluble intercellular adhesion molecule-1 (sICAM-1) level as a predictor of future acute coronary events in patients with chronic coronary heart disease (CHD). BACKGROUND: Increased sICAM-1 concentration has been shown to be associated with the incidence of CHD in healthy persons. Its significance in patients with CHD has been scarcely investigated. METHODS: We designed a prospective, nested case-control study. Sera were collected from patients with CHD enrolled in a secondary prevention trial that evaluated the efficacy of bezafibrate in reducing coronary events. We measured baseline sICAM-1 concentration in the sera of patients who developed subsequent cardiovascular events (cases: n = 136) during follow-up (mean: 6.2 years) and in age- and gender-matched controls (without events: n = 136). RESULTS: Baseline serum concentrations of sICAM-1 were significantly higher in cases versus controls (375 vs. 350 ng/ml; p < 0.05). Each 100 ng/ml increase in sICAM-1 concentration was associated with 1.27 (95% confidence interval [CI]: 1.00 to 1.63) higher relative odds of coronary events. Soluble ICAM-1 concentration in the highest quartile (>394 ng/ml) was associated with significantly higher odds of coronary events (compared with the lowest quartile), even after multivariate adjustment (2.31, 95% CI: 1.02 to 5.50). After adding fibrinogen and total white blood cell count to the multivariate model, the relative odds were 2.12 (95% CI: 0.88 to 5.35) and 2.70 (95% CI: 1.10 to 7.05), respectively. CONCLUSIONS: Elevated sICAM-1 concentration in CHD patients is associated with increased risk of future coronary events independent of other traditional risk factors.     

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.     

Diabetes and all-cause and coronary heart disease mortality among US male physicians

BACKGROUND: While diabetes has long been associated with increased risk of coronary heart disease (CHD), the magnitude of risk of diabetes-related CHD is uncertain. OBJECTIVE: To evaluate the impact of diabetes and prior CHD on all-cause and CHD mortality. METHODS: In a prospective cohort study of 91 285 US male physicians aged 40 to 84 years, participants were divided into 4 groups: (1) a reference group of 82 247 men free of both diabetes and CHD (previous myocardial infarction and/or angina) at baseline, (2) 2317 men with a history of diabetes but not CHD, (3) 5906 men with a history of CHD but not diabetes, and (4) 815 men with a history of both diabetes and CHD. Rates of all-cause and CHD mortality were compared in these groups. RESULTS: Over 5 years (49 7952 person-years of follow-up), 3627 deaths from all causes were documented, including 1242 deaths from CHD. Compared with men with no diabetes or CHD, the age-adjusted relative risk of death from any cause was 2.3 (95% confidence interval [CI], 2.0-2.6) among men with diabetes and without CHD, 2.2 (95% CI, 2.0-2.4) among men with CHD and without diabetes, and 4.7 (95% CI, 4.0-5.4) among men with both diabetes and CHD. The relative risk of CHD death was 3.3 (95% CI, 2.6-4.1) among men with diabetes and without CHD, 5.6 (95% CI, 4.9-6.3) among men with CHD and without diabetes, and 12.0 (95% CI, 9.9-14.6) among men with both diabetes and CHD. Multivariate adjustment for body mass index, smoking status, alcohol intake, and physical activity as well as stratification by these variables did not materially alter these associations. CONCLUSIONS: These prospective data indicate that diabetes is associated with a substantial increase in all-cause and CHD mortality. For all-cause mortality, the magnitude of excess risk conferred by diabetes is similar to that conferred by a history of CHD; for mortality from CHD, a history of CHD is a more potent predictor of death. The presence of both diabetes and CHD, however, identifies a particularly high-risk group.     

Is exercise testing useful to improve the prediction of coronary events in asymptomatic subjects?

OBJECTIVE: The value of exercise testing (ET) in asymptomatic subjects remains controversial and is unknown in countries with a low coronary heart disease (CHD) incidence. The aim of this study was to investigate the ability of ET to improve the prediction of a first coronary event in such a population. METHODS: Using a prospective cohort study, 1051 consecutive healthy asymptomatic adults were enrolled in a cardiovascular screening program including ET. The pre-test risk of CHD was evaluated by the 10-year Framingham risk function. Positive ET was defined as a horizontal or downsloping ST-segment depression >/=1.0 mm. The primary outcome was total coronary events (CE) occurrence, including cardiac deaths, acute myocardial infarction and stable or unstable angina. The mean follow-up period was 6 years. RESULTS: Subjects were aged 18-79 years and 36% were women. A total of 89 subjects (8.5%) had a positive ET. Positive exercise testing was associated with CE occurrence in a univariate analysis only in subjects with higher pre-test risk, defined by a 10-year Framingham risk >10.4% [hazards ratio (HR)=2.61; 95% confidence interval (CI) (1.07-6.40)]. In this risk category, ET was able to provide incremental information over the major risk factors in both men and women [risk factor-adjusted HR for positive ET=2.86; 95% CI (1.14-7.20)]. This risk excess in subjects with positive ET persisted even when a coronary revascularization was performed. Subjects with intermediate pre-test probability (10-15%) and positive ET had a post-test probability of CE largely equivalent to the probability in subjects with known CHD. CONCLUSION: Additional information provided by ET in subjects with a pre-test risk at 10-years >10% should lead to a more efficient use of risk-reducing therapies than it would be the case in this risk category with the analysis of traditional risk factors only.