Marianne Hartford

N-Terminal Pro-B–Type Natriuretic Peptide and Long-Term Mortality in Acute Coronary Syndromes

Background—B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Methods and Results—Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L;P <0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). Conclusions—N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.

Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes

OBJECTIVES This study was designed to assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS). BACKGROUND Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system. METHODS Serum samples for OPG analysis were obtained within 24 h of admission in 897 ACS patients (median age 66 years, 71% men) and related to the incidence of death, heart failure (HF) hospitalizations, myocardial infarction (MI), and stroke. RESULTS A total of 261 patients died during a median follow-up of 89 months. The baseline OPG concentration was strongly associated with increased long-term mortality (hazard ratio [HR] for HR per 1 SD increase in logarithmically transformed OPG level 1.7 [range 1.5 to 1.9] p < 0.0001) and HF hospitalizations (HR 2.0 [range 1.6 to 2.5]; p < 0.0001) but weaker with recurrent MI (HR 1.3 [range 1.0 to 1.5]; p = 0.02) and not with stroke (HR 1.2 [range 0.9 to 1.6]; p = 0.35). After adjustment for conventional risk markers, including troponin I, C-reactive protein (CRP), B-type natriuretic peptide (BNP), and ejection fraction, the association remained significant for mortality (HR 1.4 [range 1.2 to 1.7]; p < 0.0001) and HF hospitalization (HR 1.6 [range 1.2 to 2.1]; p = 0.0002), but not recurrent MI. By comparison of the area under the receiver-operating characteristics curves, OPG performed similarly to BNP and ejection fraction and significantly better than CRP and troponin I as a predictor of death. CONCLUSIONS Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

Urinary Albumin Excretion — A Predictor of Risk of Cardiovascular Disease A Prospective 10-Year Follow-Up of Middle-Aged Nondiabetic Normal and Hypertensive men

To study how the risk of cardiovascular disease changes with increasing levels of urinary albumin excretion (UAE), we prospectively studied a random sample of 120 49-year-old men with a wide range of blood pressures. Based on diastolic blood pressure (DBP), the subjects were divided into normotensives (DBP < 90 mm Hg; n = 21), borderline hypertensives (DBP 90 to 94 mm Hg; n = 30), mild hypertensives (DBP 95 to 104 mm Hg; n = 45) and moderate to severe hypertensives (DBP > 105 mm Hg; n = 24). None had been previously treated for hypertension or had secondary hypertension, diabetes mellitus, or other cardiovascular diseases at baseline. Heart and kidney function and metabolic and hormonal variables were with beta-blockade, diuretics, or hydralazine. The cardiovascular morbidity during 10 years of follow-up was studied. The hypertensives were treated with beta-blockade, diuretics, or hydralazine. The cardiovascular morbidity during 10 years of follow-up was studied. The 19 subjects who developed cardiovascular disease had significantly higher baseline UAE than the group that did not (median value 16.6 mg/24 h; range 3.5 to 73, and 9.7 mg/24 h, range 0 to 308, respectively). UAE correlated to systolic blood pressure (P = .0115) and DBP (P = .031), but not to smoking behavior or serum cholesterol. The risk of cardiovascular disease was associated with UAE and smoking independently of blood pressure (P = .001 and P = .015, respectively), and the risk increased continuously with increasing UAE. The initial UAE thus emerged as an efficient and independent predictor of cardiovascular disease in middle-aged hypertensive and normotensive men. UAE appeared to be a stronger predictor than blood pressure and serum cholesterol.

Effect of a media campaign on delay times and ambulance use in suspected acute myocardial infarction

The early phase in suspected acute myocardial infarction (AMI) is particularly critical. More than 50% of deaths from coronary artery disease occur outside the hospital mainly due to ventricular fibrillation.1 Recent experiences strongly indicate that early intervention with thrombolysis2–4 and β blockers5,6 can limit myocardial damage and thereby improve prognosis. Delay times in suspected AMI have remained stable over the years. Therefore, a media campaign was started in the urban area of Goteborg, Sweden, with the intention to shorten delay times and to increase ambulance use in patients with suspected AMI.

Prognosis in myocardial infarction in relation to gender

We studied 921 consecutive patients admitted to a single hospital for acute myocardial infarction during a period of 21 months and related their prognosis to gender. Women (n = 300, 33%) were on average 7 years older (p < 0.001) and more frequently had a previous history of hypertension (p < 0.001) and congestive heart failure (p < 0.001) than did men. They also tended to delay longer in seeking medical treatment and more often presented with only vague symptoms (p < 0.05). The in-hospital mortality for women was 19% versus 12% for men (p < 0.01). Women more often showed signs of congestive heart failure (p < 0.05) despite smaller infarcts as estimated from enzyme levels (p < 0.05). Total mortality during 1 year was 36% in women and 25% in men (p < 0.01). In a multivariate analysis, female gender did not appear as an independent risk factor for death. During 1 year of follow-up no differences in morbidity were observed between the sexes. We conclude that if women fare worse than men after suffering an acute myocardial infarction, the increased mortality is accounted for by older age.

Prognostic value of circulating chromogranin A levels in acute coronary syndromes

Aims To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs). Methods and results We measured circulating CgA levels on day 1 in 1268 patients (median age 67 years, 70% male) with ACS admitted to a single coronary care unit of a Scandinavian teaching hospital. The merit of CgA as a biomarker was evaluated after adjusting for conventional cardiovascular risk factors. During a median follow-up of 92 months, 389 patients (31%) died. The baseline CgA concentration was strongly associated with increased long-term mortality [hazard ratio per 1 standard deviation increase in logarithmically transformed CgA level: 1.57 (1.44–1.70), P < 0.001], heart failure hospitalizations [1.54 (1.35–1.76), P < 0.001], and recurrent myocardial infarction (MI) [1.27 (1.10–1.47), P < 0.001], but not stroke. After adjustment for conventional cardiovascular risk markers, the association remained significant for mortality [hazard ratio 1.28 (1.15–1.42), P < 0.001] and heart failure hospitalization [hazard ratio 1.24 (1.04–1.47), P = 0.02], but not recurrent MI. Conclusion CgA is an independent predictor of long-term mortality and heart failure hospitalizations across the spectrum of ACSs and provides incremental prognostic information to conventional cardiovascular risk markers.

Determinants of an impaired quality of life five years after coronary artery bypass surgery

OBJECTIVE To identify determinants of an inferior quality of life (QoL) five years after coronary artery bypass grafting (CABG). SETTING University hospital. PARTICIPANTS Patients from western Sweden who underwent CABG between 1988 and 1991. MAIN OUTCOME MEASURES Questionnaires for evaluating QoL before CABG and five years after operation. Three different instruments were used: the Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the physical activity score (PAS). RESULTS 2121 patients underwent CABG, of whom 310 died during five years’ follow up. Information on QoL after five years was available in 1431 survivors (79%). There were three independent predictors for an inferior QoL with all three instruments: female sex, a history of diabetes mellitus, and a history of chronic obstructive pulmonary disease. Multivariate analysis showed that a poor preoperative QoL was a strong independent predictor for an impaired QoL five years after CABG. An impaired QoL was also predicted by previous disease. CONCLUSIONS Female sex, an impaired QoL before surgery, and other diseases such as diabetes mellitus are independent predictors for an impaired QoL after CABG in survivors five years after operation.

An evaluation of the results of media and educational campaigns designed to shorten the time taken by patients with acute myocardial infarction to decide to go to hospital.

OBJECTIVE: To describe the benefits and pitfalls of educational campaigns designed to reduce the delay between the onset of acute myocardial infarction (AMI) and its treatment. METHODS: All seven educational campaigns reported between 1982 and 1994 were evaluated. RESULTS: The impact on delay time ranged from a reduction of patient decision time by 35% to no reduction. One study reported a sustained reduction that resulted in the delay time being halved during the three years after the campaign. The use of ambulances did not increase. Only one study reported that survival was unaffected. There was a temporary increase in the numbers of patients admitted to the emergency department with non-cardiac chest pain in the initial phase of educational campaigns. CONCLUSION: The challenge of shortening the delay between the onset of infarction and the start of treatment remains. The campaigns so far have not been proved to be worthwhile and it is not certain that further campaigns will do better. New media campaigns should be run to establish whether a different type of message is more likely to change the behaviour of people in this life-threatening situation.

Improvement in quality of life differs between women and men after coronary artery bypass surgery

Abstract. Sjöland H, Wiklund I, Caidahl K, Hartford M, Karlsson T, Herlitz J (Sahlgrenska University Hospital, Göteborg, and Astra Hässle AB, Mölndal, Sweden). Improvement in quality of life differs between women and men after coronary artery bypass surgery. J Intern Med 1999; 245: 445–454.

Role of the CHADS2 Score in Acute Coronary Syndromes: Risk of Subsequent Death or Stroke in Patients With and Without Atrial Fibrillation

BACKGROUND Atrial fibrillation (AF) is common in patients with acute coronary syndromes (ACS). We aimed to describe the value of the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack) score as a risk assessment tool for mortality and stroke in patients with ACS, irrespective of the presence or absence of AF. METHODS Consecutive patients with ACS admitted to the coronary care unit were prospectively included in a risk stratification study. We calculated the CHADS(2) scores from the data collected at admission, and all patients were followed until January 1, 2007, or death. RESULTS Of 2,335 patients with ACS in this study, 442 (age 71 ± 8 years, 142 women) had AF. Their mean CHADS(2) score was 1.6 ± 1.4 vs 1.0 ± 1.1 in patients without AF (P < .0001). The all-cause mortality at 10 years was strongly associated with the CHADS(2) score in patients with AF (hazard ratio [HR] and 95% CI per unit increase in the six-grade CHADS(2) score, 1.21 [1.07-1.36]; P = .002), but the same association was also present in patients without AF (HR 1.38 [1.28-1.48], P < .0001), after adjustment for potential confounders. The more complicated GRACE (Global Registry of Acute Coronary Events) risk score provided a better prediction for short- and long-term mortality than the simpler CHADS(2) score (P < .0001). Hospitalization for stroke was significantly associated with the CHADS(2) score in patients without AF (but not in those with AF) after adjustment (HR 1.46 [1.27-1.68], P < .0001). CONCLUSIONS In patients with ACS, AF is associated with poor prognosis. The CHADS(2) score developed for AF has even greater prognostic value in patients who do not have AF, and it may help to identify patients with high risk for subsequent stroke or death and a need for optimization of risk-reducing treatment.