Comparative outcomes of percutaneous coronary interventions in diabetics vs non-diabetics with prior coronary artery bypass grafting.

AIMS: To determine the influence of diabetes on outcome after percutaneous coronary intervention in patients with prior coronary artery bypass grafting. METHODS AND RESULTS: Patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention from 1 January 1996, to 31 August 2000, were divided into two groups based on whether or not they had diabetes, excluding patients with acute infarction or shock. Cox proportional hazards models were utilized to estimate the association between diabetes and adverse events. One thousand one hundred and fifty-three post-coronary artery bypass grafting percutaneous coronary intervention patients were identified (326 diabetics and 827 non-diabetics). Diabetics were younger, more likely to have hypertension, heart failure, and lower ejection fraction. Procedural characteristics and angiographic and procedural success rates were similar. Diabetes was associated with increased mortality (hazard ratio 1.58, 95% confidence intervals 1.10-2.27). Diabetes did not have a significant effect on mortality in patients treated for single-territory coronary disease (hazard ratio 1.44, 95% confidence intervals 0.69-3.02), but did in patients with multi-territory disease (hazard ratio 1.79, 95% confidence intervals 1.16-2.76). However, in diabetics with multi-territory disease who were completely revascularized with percutaneous coronary intervention, mortality was comparable to non-diabetics (hazard ratio 1.32, 95% confidence intervals 0.57-3.03). CONCLUSION: Among percutaneous coronary intervention patients with prior coronary artery bypass grafting, diabetes portends an adverse prognosis.

Effect of time since onset of risk factors on the occurrence of ischemic stroke.

OBJECTIVE: To determine the effect of time since onset of risk factors on the modeling of risk factors for ischemic stroke. METHODS: The resources of the Rochester Epidemiology Project allowed identification of the 1,397 incident cases of ischemic stroke and age- and sex-matched control subjects from the population for 1970 through 1989. These cases and controls permitted the development of a multiple conditional logistic regression model to estimate the odds ratios of ischemic stroke for various risk factors. The time since onset variables for each risk factor were then added to the model to determine which were significant and to assess their impact on variables in the model. RESULTS: The time since onset variables for congestive heart failure and TIA were the only variables of this type included in the resultant model. Each showed the highest risk for stroke soon after the onset of the risk factor. In addition, the influence of congestive heart failure was higher at younger ages. Hypertension (with or without left ventricular hypertrophy) increases the risk for stroke but has a diminishing influence with increasing age. In addition, persons with left ventricular hypertrophy are at a higher risk than those with hypertension alone, although this difference also decreases with age. The time since onset variables pertaining to systolic hypertension at 140 to 159 mm Hg, 160 to 179 mm Hg, and > or =180 mm Hg were not significant in any analysis. CONCLUSIONS: TIA and congestive heart failure were the only risk factors for stroke for which time since onset was significant in the model for predicting ischemic stroke.

T-cell immunity in acute coronary syndromes.

Acute coronary syndromes (ACS) are complications of atherosclerotic vascular disease that are triggered by the sudden rupture of an atheroma. Atherosclerotic plaque stability is determined by multiple factors, of which immune and inflammatory pathways are critical. Unstable plaque is characterized by an infiltrate of T cells and macrophages, thereby resembling a delayed hypersensitivity reaction. On activation, T cells secrete cytokines that regulate the activity of macrophages, or the T cells may differentiate into effector cells with tissue-damaging potential. Constitutive stimulation of T cells and macrophages in ACS is not limited to the vascular lesion but also involves peripheral immune cells, suggesting fundamental abnormalities in homeostatic mechanisms that control the assembly, turnover, and diversity of the immune system as a whole. This review gives particular attention to the emergence of a specialized T-cell subset, natural killer T cells, in patients with ACS. Natural killer T cells have proinflammatory properties and the capability of directly contributing to vascular injury.

Molecular fingerprint of interferon-gamma signaling in unstable angina.

BACKGROUND: Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-gamma. IFN-gamma induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-gamma driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10. METHODS AND RESULTS: Peripheral blood mononuclear cells were stained for expression of CD64 on CD14(+) monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-gamma in vitro, with accelerated transcriptional competency of CD64. IP-10-specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients (P<0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-gamma signaling in vivo. CONCLUSIONS: Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-gamma triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-gamma. IFN-gamma may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.

Time trends in the prevalence of atherosclerosis: a population-based autopsy study.

PURPOSE: Mortality from coronary heart disease is declining but little is known about trends in the prevalence of atherosclerosis. Autopsy rates in Olmsted County, Minnesota, are higher than the national average, offering an opportunity to address this matter. In this study, we determined the prevalence of anatomic coronary disease among autopsied Olmsted County residents and examined the generalizability of these findings. SUBJECTS AND METHODS: Reports of the 2,562 autopsies performed between 1979 and 1994 on Olmsted County residents > or =20 years of age were reviewed for the presence of coronary disease. RESULTS: Among autopsied decedents less than 60 years old at death and among coroner's cases, the prevalence of anatomic coronary disease declined with time (P for trend = 0.05); no trend was detected among older persons or noncoroner's cases. By logistic regression analysis, the crude odds ratio ([OR] per 5 years) for the association between time and anatomic coronary disease was 0.94 (95% confidence interval [CI]: 0.86 to 1.03; P = 0.18]. Age, sex, and antemortem diagnosis of heart disease were also strongly related to the presence of disease. After adjustment for sex and antemortem diagnosis of heart disease, the prevalence of anatomic coronary disease decreased more in younger people than in older people (age 40 years: OR 0.43 [95% CI: 0.24 to 0.80]; age 60 years: OR 0.62 [95% CI: 0.45 to 0.87]; age 80 years: OR 0.89 [95% CI: 0.64 to 1.23]). CONCLUSION: The prevalence of anatomic coronary disease at autopsy decreased between 1979 and 1994, particularly among younger people, supporting the notion that the burden of coronary disease has shifted toward the elderly. These results suggest that the decreased incidence of coronary artery disease has contributed to the recent decrease in coronary mortality, particularly among younger people.

Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.

BACKGROUND: Unstable angina (UA) is associated with systemic inflammation and with expansion of interferon-gamma-producing T lymphocytes. The cause of T-cell activation and the precise role of activated T cells in plaque instability are not understood. METHODS AND RESULTS: Peripheral blood T cells from 34 patients with stable angina and 34 patients with UA were compared for the distribution of functional T-cell subsets by flow cytometric analysis. Clonality within the T-cell compartment was identified by T-cell receptor spectrotyping and subsequent sequencing. Tissue-infiltrating T cells were examined in extracts from coronary arteries containing stable or unstable plaque. The subset of CD4(+)CD28(null) T cells was expanded in patients with UA and infrequent in patients with stable angina (median frequencies: 10.8% versus 1.5%, P<0.001). CD4(+)CD28(null) T cells included a large monoclonal population, with 59 clonotypes isolated from 20 UA patients. T-cell clonotypes from different UA patients used antigen receptors with similar sequences. T-cell receptor sequences derived from monoclonal T-cell populations were detected in the culprit but not in the nonculprit lesion of a patient with fatal myocardial infarction. CONCLUSIONS: UA is associated with the emergence of monoclonal T-cell populations, analogous to monoclonal gammopathy of unknown significance. Shared T-cell receptor sequences in clonotypes of different patients implicate chronic stimulation by a common antigen, for example, persistent infection. The unstable plaque but not the stable plaque is invaded by clonally expanded T cells, suggesting a direct involvement of these lymphocytes in plaque disruption.

The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. Bypass Angioplasty Revascularization Investigation Investigators.

BACKGROUND: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. METHODS: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. RESULTS: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarctions, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. CONCLUSIONS: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.

Sudden death in mitral regurgitation due to flail leaflet.

OBJECTIVES: We sought to assess the incidence and determinants of sudden death (SUD) in mitral regurgitation due to flail leaflet (MR-FL). BACKGROUND: Sudden death is a catastrophic complication of MR-FL. Its incidence and predictability are undefined. METHODS: The occurrence of SUD was analyzed in 348 patients (age 67 +/- 12 years) with MR-FL diagnosed echocardiographically from 1980 through 1994. RESULTS: During a mean follow-up of 48 +/- 41 months, 99 deaths occurred under medical treatment. Sudden death occurred in 25 patients, three of whom were resuscitated. The sudden death rates at five and 10 years were 8.6 +/- 2% and 18.8 +/- 4%, respectively, and the linearized rate was 1.8% per year. By multivariate analysis, the independent baseline predictors of SUD were New York Heart Association (NYHA) functional class (p = 0.006), ejection fraction (p = 0.0001) and atrial fibrillation (p = 0.059). The yearly linearized rate of sudden death was 1% in patients in functional class I, 3.1% in class II and 7.8% in classes III and IV. However, of 25 patients who had SUD, at baseline, 10 (40%) were in functional class I, 9 (36%) were in class II and only 6 (24%) in class III or IV. In five patients (20%), no evidence of risk factors developed until SUD. In patients with an ejection fraction > or =60% and sinus rhythm, the linearized rate of SUD was not different in functional classes I and II (0.8% per year). Surgical correction of MR (n = 186) was independently associated with a reduced incidence of SUD (adjusted hazard ratio [95% confidence interval] 0.29 [0.11 to 0.72], p = 0.007). CONCLUSIONS: Sudden death is relatively common in patients with MR-FL who are conservatively managed. Patients with severe symptoms, atrial fibrillation and reduced systolic function are at higher risk, but notable rates of SUD have been observed without these risk factors. Correction of MR appears to be associated with a reduced incidence of SUD, warranting early consideration of surgical repair.

Perturbation of the T-cell repertoire in patients with unstable angina.

BACKGROUND: Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA). METHODS AND RESULTS: Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4(+) and CD8(+) T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4(+) and CD8(+) T cells producing IFN-gamma, whereas patients with SA had higher frequencies of IL-2(+) and IL-4(+) CD4(+) T cells. Expansion of the IFN-gamma( +) T-cell population in UA persisted for at least 3 months. Increased production of IFN-gamma in UA could be attributed to the expansion of an unusual subset of T cells, CD4(+)CD28(null) T cells. CONCLUSIONS: Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-gamma production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-gamma is produced by CD4(+)CD28(null) T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4(+)CD28(null) T cells may result from persistent antigenic stimulation.

Trends in coronary revascularization 1989 to 1997: the Bypass Angioplasty Revascularization Investigation (BARI) survey of procedures.

Use of catheter-based and surgical coronary revascularization has steadily increased in North America. Introduction of catheter-based "new devices," including intracoronary stents, has expanded the range of patients who can be treated with percutaneous approaches. We sought to address trends in the practice of catheter-based and surgical coronary revascularization during 1989 to 1997. The 17 North American institutions participating in the NHLBI Bypass Angioplasty Revascularization Investigation (BARI) periodically completed a 5-working day survey of all surgical and catheter-based coronary revascularizations. Data collected included patient demographics, vessel disease, prior interventions, and use of new devices or minimally invasive surgical techniques. The proportion of all procedures that were catheter based (vs surgical) increased from 52.1% in 1989/1990 to 62.0% in 1997 (p <0.001). Among surgically treated patients, prevalence of prior bypass surgery decreased from 13.4% in 1989/1990 to 7.5% in 1997 (p <0.001). In 1997, 3% of surgical procedures used minimal incisions or were performed without cardiopulmonary bypass. Among patients undergoing catheter-based intervention, prevalence of left main disease increased from 2.2% to 5.7% (p <0.001), myocardial infarction within 24 hours increased from 2.4% to 9.7% (p <0.001), and prior bypass surgery increased from 16.2% to 20.8% (p = 0.056). Use of new devices increased from 11.6% of catheter-based procedures in 1990 to 67.0% in 1997 (p <0.001). Compared with the early 1990s, catheter-based revascularization is currently more commonly used for patients with acute myocardial infarction, prior bypass surgery, or severe left main narrowing. These trends are likely due to the proliferation of new devices, especially intracoronary stents, since the mid 1990s.

Trends in heart disease deaths in Olmsted County, Minnesota, 1979-1994.

BACKGROUND: Although age-adjusted heart disease mortality has declined since the 1960s, this decline may not have applied equally to all subgroups. OBJECTIVE: To examine recent trends in heart disease mortality, specifically in women and in the elderly. METHODS: Age- and sex-specific heart disease mortality (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 390-398, 402, 404-429) in Olmsted County, Minnesota, between 1979 and 1994 were studied. RESULTS: The total number of heart disease deaths was 3095; 1578 (51%) occurred in women and 1984 (64%) in persons aged 75 years or older. Most heart disease deaths (77%) were coronary disease deaths (ICD-9-CM codes 410-414). Age-adjusted heart disease mortality rates declined from 123 per 100,000 (95% confidence interval [CI], 102-144/100,000) in 1979 to 81 per 100,000 (95% CI, 67-95/100,000) in 1994. Poisson regression analyses indicated that the trends differed according to sex and age. For women, the relative risk (RR) of heart disease death in 1994 compared with 1979 was 0.69 vs 0.53 for men (P = .06). This equates to a decline in heart disease mortality of 2.5% per year in women or 32% over the period and 4.2% per year in men or 47% over the period. The decline was less pronounced as age increased (P < .001). For 60-year-old women, the RR for 1994 compared with 1979 was 0.59, whereas for 80-year-old women, the RR for 1994 compared with 1979 was 0.76. For men, the RR for 1994 compared with 1979 was 0.60 for 80-year-old men vs 0.46 for 60-year-old men. CONCLUSIONS: Between 1979 and 1994, in Olmsted County, the decline in heart disease mortality was of lesser magnitude in women and in the elderly, emphasizing the importance of age- and sex-specific trends to characterize time patterns in heart disease deaths to target preventive measures.

Is a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization acceptable in nondiabetic patients who are candidates for coronary artery bypass graft surgery? The Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome. BACKGROUND: Complete angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear. METHODS: Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended. RESULTS: At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), vet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08). CONCLUSIONS: Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain.

Effect of age in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial.

BACKGROUND: The influence of age on the relative success of either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) in patients requiring myocardial revascularization continues to be controversial. METHODS: In the Bypass Angioplasty Revascularization Investigation (BARI) trial, 1,829 patients with symptomatic multivessel coronary artery disease requiring revascularization were randomly assigned to undergo either CABG or PTCA. RESULTS: Seven hundred nine patients (39%) were 65 to 80 years old at baseline; the other 1,120 were younger than 65 years. The in-hospital 30-day mortality rate for PTCA and CABG in the younger patients was 0.7% and 1.1%, respectively, and that for patients 65 years or older was 1.7% and 1.7%, respectively. In older compared with younger patients, stroke was more common after CABG (1.7% versus 0.2%, p = 0.015) and heart failure or pulmonary edema was more common after PTCA (4.0 versus 1.3%, p = 0.011). In both age groups, CABG resulted in greater relief of angina and fewer repeat procedures. The 5-year survival rate in patients younger than 65 years was 91.5% for CABG and 89.5% for PTCA. In patients 65 years or older, the 5-year survival rate was 85.7% for CABG and 81.4% for PTCA. Cardiac mortality at 5 years was greater in patients assigned to the PTCA group than in those assigned to the CABG group. However, no significant treatment differences were noted in cardiac mortality when only nondiabetic patients were examined. CONCLUSIONS: Within the context of the Bypass Angioplasty Revascularization Investigation trial, older patients with multivessel coronary disease do well with either PTCA or CABG. Compared with younger patients, older patients had less recurrent angina and were less likely to undergo repeat procedures, particularly among those assigned to undergo CABG. Cardiac mortality was greater in patients 65 years or older assigned to undergo PTCA; however, this difference was not noted when treated diabetic patients were excluded from analysis.

Coronary revascularization in diabetic patients: a comparison of the randomized and observational components of the Aypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS: Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS: BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications.

BACKGROUND: Surgical correction of mitral regurgitation in patients with no or mild symptoms remains controversial, particularly because the impact of preoperative symptoms on postoperative outcome is unknown. METHODS AND RESULTS: The long-term outcome of 478 patients with organic mitral regurgitation (199 in NYHA functional class I/II and 279 in class III/IV before surgery) operated on between 1984 and 1991 was analyzed. In patients in NYHA class I/II before surgery compared with those in class III/IV, postoperative long-term survival was higher (at 10 years, 76+/-5% versus 48+/-4%, P<0.0001), with lower operative mortality (0.5% versus 5.4%, P=0.003) and better late survival (P<0.0001). Comparison of observed and expected survival showed identical curves in patients in class I/II before surgery (P=0.18), whereas excess mortality was observed in patients in class III/IV before surgery (P<0.0001). Excess mortality associated with severe symptoms was also confirmed in all subgroups (all P<0.003) and in multivariate analysis (P=0.0036; adjusted hazard ratio [95% CI], 1.81 [1.21 to 2.70]). CONCLUSIONS: In patients with organic mitral regurgitation, preoperative functional class III/IV symptoms are associated with excess short- and long-term postoperative mortality independently of all baseline characteristics. These data should lead to consideration of surgical correction of severe organic mitral regurgitation when no or minimal symptoms are present in patients at low operative risk, especially if repair is feasible.

Excess mortality due to coronary artery disease after valve surgery. Secular trends in valvular regurgitation and effect of internal mammary artery bypass.

BACKGROUND: During the 1980s, mortality from coronary artery disease (CAD) decreased markedly in the United States. This raises the question of whether a parallel decrease occurred in excess mortality due to CAD in patients undergoing surgical correction of valvular regurgitation. METHODS AND RESULTS: Survival of 752 patients (age, 64 +/- 13 years) with isolated left-sided valvular regurgitation operated on from 1980 to 1991 was analyzed. Of 242 patients with CAD (stenosis > or = 70%), 208 had coronary artery bypass grafting. Multivariate analysis identified CAD as an independent predictor of operative mortality (odds ratio [OR] = 2.35, P = 0.012), overall (hazard ratio [HR] = 1.65, P < 0.0001) and late mortality (HR = 1.57, P = 0.0006), and postoperative congestive heart failure (HR = 2.35, P = 0.0001). Comparison of patients operated on in 1980 to 1985 with those operated on in 1986 to 1991, excess of operative, overall, and late mortality and postoperative congestive heart failure (adjusted for age and gender) related to associated CAD did not decrease significantly (P = 0.23, P = 0.64, P = 0.90, and P = 0.61, respectively). Overall survival was better for patients receiving an internal mammary artery graft than those receiving vein grafts only (HR = 0.57, P = 0.011). CONCLUSIONS: In contrast to the secular trend for decreased mortality from CAD, excess mortality related to associated CAD after surgery for valvular regurgitation has not decreased. Internal mammary artery grafts were associated with improved outcome. In patients with valvular regurgitations, these results support continued active search of associated CAD, wide use of internal mammary artery graft, and vigorous efforts for secondary prevention of complications of CAD.