Aim To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man. Methods and results Plasma MMP-2 and MMP-9 were assayed at intervals (0–12, 12–24, 24–48, 48–72, 72–96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138–262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005–0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0–12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively). Conclusion Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.

Matrix metalloproteinase (MMP) activity is central to the development of left ventricular (LV) remodelling and dysfunction after acute myocardial infarction (AMI). We assessed the relationships with LV structure and function and outcome, of tissue inhibitors of metalloproteinase-1 (TIMP-1) and MMP-9, and compared with N-terminal pro-B-type natriuretic peptide (NTproBNP). We studied 404 patients with AMI. Primary outcome measures were the associations of TIMP-1, MMP-9, and NTproBNP with death or heart failure, and with LV dimensions, function and remodelling (ΔLVEDV, change in LV end-diastolic volume between discharge and follow-up). Cut-off concentrations for prediction of death or heart failure were identified from receiver operator characteristic (ROC) curves. In multivariable analysis, TIMP-1 and NTproBNP had predictive value for LV ejection fraction pre-discharge (TIMP-1 P = 0.023; N-BNP P = 0.007) and at follow-up (TIMP-1 P = 0.001; N-BNP P = 0.003). MMP-9, TIMP-1, and NTproBNP correlated directly with LV volumes. MMP-9 (P = 0.005) and TIMP-1 (P = 0.036), but not NTproBNP, correlated with ΔLVEDV. For the combined endpoint of death or heart failure the area under the ROC curve was 0.640 for MMP-9, 0.799 for NTproBNP and 0.811 for TIMP-1. Patients with TIMP-1 > 135 ng/mL (P < 0.001) or NTproBNP >1472 fmol/mL (P < 0.001) had increased risk of endpoint. Consideration of both NTproBNP and TIMP-1 further improved risk stratification. TIMP-1 and MMP-9 correlate with echocardiographic parameters of LV dysfunction and remodelling after AMI and may identify patients at risk of subsequent LV remodelling and adverse prognosis.

Introduction: Changes to cardiac matrix are central to ventricular remodelling after acute MI and matrix metalloproteinase expression is implicated in this process. We investigated the temporal profile of MMP-3 and its relationship to LV dysfunction and prognosis following AMI. Methods: We studied 382 patients with AMI. Plasma MMP-3 was measured at 0–12, 12–24 h and for subsequent 24 h periods during admission. LV function (LVEF) was assessed by echocardiography pre-discharge and at a median of 148 days and clinical endpoints at a median of 313 days. Results: MMP-3 peaked prior to discharge thus pre-discharge levels were used in analyses. MMP-3 was associated with patient age (p<0.001), creatinine (p<0.001) and was higher in males (p<0.001) and hypertensives (p<0.001). MMP-3 inversely correlated with LVEF at follow-up (p=0.043), was higher in subjects with LVEF <40% (p=0.017) and in subjects with increasing EDV (p=0.017) or ESV (p=0.007) compared to those in whom volumes fell between visits. In the 58 patients reaching the endpoint of death or heart failure, MMP-3 was higher (p<0.001). On Kaplan–Meier analysis, subjects with levels above optimum cut off identified via ROC curves were more likely to suffer a clinical event (p=0.037). Conclusion: MMP-3 is associated with left ventricular dysfunction, adverse left ventricular remodelling and prognosis after AMI.

Objectives To compare patterns of admission to hospital and prognosis in white and South Asian patients newly admitted with heart failure, and to evaluate the effect of personal characteristics and comorbidity on outcome. Design Historical cohort study. Setting UK district health authority (population 960 000). Participants 5789 consecutive patients newly admitted with heart failure. Main outcome measures Population admission rates, incidence rates for first admission with heart failure, survival, and readmission rates. Results When compared with the white population, South Asian patients had significantly higher age adjusted admission rates (rate ratio 3.8 for men and 5.2 for women) and hospital incidence rates (2.2 and 2.9). Among 5789 incident cases of heart failure, South Asian patients were younger and more often male than white patients (70 (SD 0.6) v 78 (SD 0.1) years and 56.5% (190/336) v 49.3% (2494/5057)). South Asian patients were also more likely to have previous myocardial infarction (10.1% (n = 34) v 5.5% (n = 278)) or concomitant myocardial infarction (18.8% (n = 63) v 10.7% (n = 539)) or diabetes (45.8% (n = 154) v 16.2% (n = 817), all P < 0.001). A trend was shown to longer unadjusted survival for both sexes among South Asian patients. After adjustment for covariables, South Asian patients had a significantly lower risk of death (hazard ratio 0.82, 95% confidence interval 0.68 to 0.99) and a similar probability of death or readmission (0.96, 0.81 to 1.09) compared with white patients. Conclusions Population admission rates for heart failure are higher among South Asian patients than white patients in Leicestershire. At first admission South Asian patients were younger and more often had concomitant diabetes or acute ischaemic heart disease than white patients. Despite major differences in personal characteristics and risk factors between white and South Asian patients, outcome was similar, if not better, in South Asian patients.

—The physiological effects of angiotensin-converting enzyme (ACE) inhibition may be in part mediated by bradykinin. We investigated the effect of coadministration of the specific bradykinin B₂receptor antagonist icatibant on hemodynamic and neurohormonal responses to acute intravenous ACE inhibition in normal men on a normal sodium diet. We performed a 4-phase, double-blind, double-dummy, placebo-controlled study in 12 male volunteers. The bradykinin antagonist icatibant (10 mg IV) was coadministered over the first 15 minutes of a 2-hour infusion of the ACE inhibitor perindoprilat (1.5 mg IV). Perindoprilat inhibited ACE activity and elicited the expected changes in active renin concentration and angiotensin peptides. Over the 3 hours after the start of drug infusion, perindoprilat lowered and icatibant increased mean arterial blood pressure (eachP<0.0005 versus placebo). Coadministration of icatibant attenuated the mean arterial blood pressure response to perindoprilat (P<0.0005) but had no effect on neurohormonal responses to perindoprilat. Our study indicates that the bradykinin B₂receptor antagonist icatibant attenuates the short-term blood pressure–lowering effect of acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B₂receptor antagonism alone increases resting blood pressure. Bradykinin may be involved in the control of blood pressure in the resting state in humans.