Randomized clinical trials have shown that statins can reduce mortality after acute myocardial infarction (AMI). However, the impact of changes in patterns of statin use, particularly stopping statins, on survival post-AMI is unknown. Our objective was to estimate the extent to which different patterns of statin use are associated with post-AMI mortality.
Population-based, cohort study, from 2002 through 2004 in the United Kingdom General Practice Research Database (GPRD), involving patients surviving 90 days after their first AMI. Past statin use was defined as any statin prescription within 90 days before AMI; statin use post-AMI as any statin prescription within 90 days after AMI. Cohort entry was at day 90 post-AMI; subjects were followed for 1 year. Four groups were identified: (i) non-users (patients never on statins); (ii) users (on statins before and continued post-AMI); (iii) starters (started statins after the event); and (iv) stoppers (stopped statins after the event). Hazard ratios (HRs) were estimated using Cox proportional hazards model. The main outcome measure was 1-year all-cause mortality. The cohort included 9939 AMI survivors (mean age: 68.4 ± 12.8 years; 60.3% men), 22.7% of whom were not prescribed a statin post-AMI. When the non-user group (n = 2124) was considered as the reference, the adjusted HRs (95% confidence intervals) of death were 0.84 (0.66–1.09) for users (n = 2026), 0.72 (0.57–0.90) for starters (n = 5652), and 1.88 (1.13–3.07) for stoppers (n = 137). Stoppers of control medications (aspirin, β-blockers, and proton pump inhibitors) were not associated with increased mortality.
Discontinuation of statins in survivors of a first AMI was relatively rare in this cohort. However, statin discontinuation was associated with higher total mortality and this may represent a biological rebound or/and a risk-treatment mismatch phenomenon, where treatment is withdrawn from very ill patients. While awaiting further research, at present statin use should only be withdrawn under judicious clinical supervision.
N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are altered in renal failure. This study examined the effect of baseline and change from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis patients.
On the basis of the German Diabetes and Dialysis Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM) haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on pre-specified, adjudicated endpoints was investigated: sudden death (SD; n = 160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612). Patients with baseline NT-pro-BNP ≥9252 pg/mL (fourth quartile) exhibited a more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.0–8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2–3.3), CVE (HR 2.0; 95% CI 1.5–2.7), and mortality (HR 2.1; 95% CI 1.6–2.7) compared with patients with baseline NT-pro-BNP ≤ 1433 pg/mL (first quartile). Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality. Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1–2.0). Neither baseline nor change in NT-pro-BNP was significantly associated with MI.
Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves outcome needs to be evaluated prospectively.
Some studies show coronary heart disease (CHD) to be a risk factor for cognitive function while others report no association between the two. We examined the effect of CHD history and duration on cognition in a middle-aged population.
Data come from the Whitehall II study of 10 308 participants (33% women), aged 35–55 years at baseline (Phase 1; 1985–88). CHD events were assessed up to Phase 7 (2002–04) when 5837 participants (28.4% women) undertook six cognitive tests: reasoning, vocabulary, phonemic and semantic fluency, memory and the mini-mental-state-examination (MMSE); standardized to T-scores (mean = 50, standard deviation = 10). Analysis of covariance was used first to model the association between CHD history and cognition and then to examine the effect of time since first CHD event (in the last 5 years, 5–10 years ago, >10 years ago). Among men, in analyses adjusted for age, education, marital status and medication for cardiovascular disease, CHD history was associated with lower T-scores on reasoning [–1.16; 95% confidence interval (CI) = –2.07, –0.25], vocabulary (–2.11; 95% CI = –3.01, –1.21), and the MMSE (–1.45; 95% CI = –2.42, –0.49). In women, these effects were also evident for phonemic and semantic fluency. Among men, the trend within CHD cases suggested progressively lower scores on reasoning, vocabulary and semantic fluency among those with longer duration of CHD.
Our findings go some way towards suggesting an association between CHD history and cognitive performance in middle-aged adults.
To evaluate the occurrence of late and very late stent thrombosis (ST) following elective drug-eluting stent (DES) implantation in unprotected left main coronary artery (LMCA) stenosis in a large multicentre registry.
All 731 consecutive patients who had sirolimus- or paclitaxel-eluting stent electively implanted in de novo lesions on unprotected LMCA in five centres were included. ST was defined according to Academic Research Consortium definitions. Four (0.5%) patients had a definite ST: three early (two acute and one subacute) and one late ST, no cases of very late definite ST were recorded. All patients survived from the event. Three patients had a probable ST. Therefore, 7/731 (0.95%) patients had a definite or a probable ST and all were on dual antiplatelet therapy at the time of the event. Possible (eight late and 12 very late) ST occurred in 20 (2.7%) patients. At 29.5 ± 13.7 months follow-up, a total of 45 (6.2%) patients had died; 31 (4.2%) of cardiac death. Ninety five (12.9%) patients had a target-vessel and 76 (10.4%) a target-lesion revascularization. Angiographic follow-up was performed in 548 patients (75%): restenosis occurred in 77 (14.1%) patients.
Elective treatment of LMCA stenosis with DES appears safe with a 0.9% incidence of definite and probable ST at 29.5 ± 13.7 months.
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 (LVEDV, 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 LVEDV. 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.
To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain.
We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37–84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = –0.115, P < 0.01) as well as attention and executive functions (ß = –0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups.
Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.
We evaluated the accuracy of 64-slice computed tomography (CT) to identify ischaemic aetiology of heart failure (IHF).
Ninety-three consecutive patients in sinus rhythm with dilated cardiomyopathy but without suspicion of coronary artery disease (CAD) were enrolled when admitted for angiography. Accuracy of CT to detect significant stenosis (>50% lumen narrowing) was compared with quantitative coronary angiography. IHF was defined as a significant stenosis on left main or proximal left anterior descending artery or two or more vessels. Forty-three out of 1395 segments (3%) were heavily calcified and excluded. CT correctly assessed 103 of 142 (73%) significant stenosis and identified 46 of 50 (92%) patients without and 42 of 43 (98%) patients with CAD, 60 of 62 (97%) patients without and 28 of 31 (90%) patients with IHF. Overall, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT for identifying CAD by segment was 96, 73, 99, 92, and 97%, respectively; by patient was 95, 98, 92, 91, and 98%, respectively; and for identifying IHF was 95, 90, 97, 93, and 95%, respectively.
Non-invasive 64-slice CT assessment of the extent of CAD may offer a valid alternative to angiography for the diagnosis of IHF.
We hypothesized a relationship between virtual histology intravascular ultrasound (VH-IVUS) findings and risk factors histopathologically associated with sudden coronary death (SCD) in men: cigarette smoking and an increased total cholesterol-to-high-density lipoprotein cholesterol (HDL-C) ratio (TC/HDL > 5).
We assessed volumetric VH-IVUS parameters in a consecutive series of 473 male patients: fibrous, fibro-fatty, dense calcium (DC), necrotic core (NC), and a calculated NC/DC ratio. Patients’ age was 61 ± 11 years, with 27% smokers and 69% having a lipid disorder. The NC/DC ratio was the only VH-IVUS parameter related to both TC/HDL ratio (r = 0.18, P= 0.0008) and low-density lipoprotein cholesterol levels (r = 0.17, P= 0.002); had a negative correlation with HDL-C levels (r = –0.11, P= 0.03); and was higher for smokers [median 1.98 (1.35–3.18)] vs. non-smokers [median 1.70 (1.23–2.53), P= 0.006]. An NC/DC value >3 was the threshold that best identified smokers and/or patients presenting TC/HDL >5 (odds ratio 3.0, 95% CI 1.7–4.9, P= 0.0001), and receiver-operator curves showed the superiority of the NC/DC ratio [area under curve (AUC) 0.64, P < 0.0001] over %DC (AUC 0.58, P= 0.006) or %NC (AUC 0.51, P= 0.43) to identify these patients.
The ratio of NC to calcification detected by VH-IVUS in diseased coronary segments is related to known risk factors for SCD and, thus, may be associated with a worse prognosis.
To evaluate the feasibility and diagnostic performance of high spatial resolution myocardial perfusion cardiac magnetic resonance (perfusion-CMR).
Fifty-four patients underwent adenosine stress perfusion-CMR. An in-plane spatial resolution of 1.4 x 1.4 mm2 was achieved by using 5x k-space and time sensitivity encoding (k–t SENSE). Perfusion was visually graded for 16 left ventricular and two right ventricular (RV) segments on a scale from 0 = normal to 3 = abnormal, yielding a perfusion score of 0–54. Diagnostic accuracy of the perfusion score to detect coronary artery stenosis of >50% on quantitative coronary angiography was determined. Sources and extent of image artefacts were documented.
Two studies (4%) were non-diagnostic because of k–t SENSE-related and breathing artefacts. Endocardial dark rim artefacts if present were small (average width 1.6 mm). Analysis by receiver–operating characteristics yielded an area under the curve for detection of coronary stenosis of 0.85 [95% confidence interval (CI) 0.75–0.95] for all patients and 0.82 (95% CI 0.65–0.94) and 0.87 (95% CI 0.75–0.99) for patients with single and multi-vessel disease, respectively. Seventy-four of 102 (72%) RV segments could be analysed.
High spatial resolution perfusion-CMR is feasible in a clinical population, yields high accuracy to detect single and multi-vessel coronary artery disease, minimizes artefacts and may permit the assessment of RV perfusion.
Epidermal fatty-acid-binding protein (E-FABP) is highly homologous to adipocyte FABP (A-FABP), which mediates obesity-related metabolic syndrome (MetS), diabetes and atherosclerosis in animals. Combined deficiency of E-FABP and A-FABP protects against the MetS and atherosclerosis in mice. This study investigated the association of serum E-FABP with cardio-metabolic risk factors and carotid atherosclerosis in humans.
The presence of E-FABP in human plasma was detected by tandem mass spectrometry. Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS). The association of E-FABP with the MetS was independent of A-FABP. Furthermore, serum E-FABP correlated with carotid intima-media thickness (IMT; P < 0.001) and was independently associated with carotid IMT in men (adjusted P = 0.03).
E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.
Increasing evidence suggests that adverse prenatal environments, as indicated by low birth weight, cause long-term changes in cardiovascular physiology that predispose to circulatory disease. The mechanisms are poorly understood, most human studies have been carried out in adults and little is known about early pathophysiological changes. Therefore, we have assessed the relationship between birth weight and cardiovascular physiology in children.
In 140 healthy boys and girls (aged 7–9 years), born at term and followed prospectively, we continuously recorded blood pressure, electrocardiograms and cardiac impedance before, during, and after 10 min of psychosocial stress (Trier Social Stress Test for Children). In boys, an association of lower birth weight with higher resting systemic arterial pressure (β = –6.8 mmHg/kg, P= 0.03) and a trend towards higher vascular resistance (β = –87 dyne s/cm5/kg, ns) were substantially strengthened following stress (β = –9.5 mmHg/kg, P= 0.003 and β = –139 dyne s/cm5/kg, P = 0.02, respectively). In girls, lower birth weight was associated with a shorter pre-ejection period (β = 8.0 ms/kg, P = 0.005) and corrected QT interval (β = 11.9 ms/kg, P = 0.003) at rest and little changed by stress.
Smaller size at birth is associated with sex-specific alterations in cardiac physiology; boys had higher systemic vascular resistance and girls had increased cardiac sympathetic activation.
Inhibition of aldosterone synthase, the key enzyme in aldosterone formation, could be an alternative strategy for mineralocorticoid-receptor antagonists in congestive heart failure (CHF), but its effect in CHF is unknown.
We compared, in rats with CHF, the effects of a 7 day and a 12 week treatment with the aldosterone synthase inhibitor FAD286 (4 mg kg–1 day–1) with those induced by spironolactone (80 mg kg–1 day–1). FAD286/spironolactone increased cardiac output without modifying arterial pressure. Long-term FAD286 and spironolactone reduced left ventricular (LV) end-diastolic pressure, LV relaxation constant, and LV dilatation, and these effects were more marked with FAD286, whereas both drugs reduced LV hypertrophy and collagen accumulation to the same extent. Long-term FAD286/spironolactone prevented CHF-related enhancement in LV ACE and reduction in LV ACE-2, but only FAD286 prevented the reduction in LV AT2 receptors. FAD286, but not long-term spironolactone, reduced the CHF-related enhancements in LV reactive oxygen species, reduced-oxidized glutathione ratio, and aortic nicotinamide adenine dinucleotide phosphate oxidase activity. FAD286 normalized the CHF-induced impairment of endothelium-dependent vasodilatation.
In experimental CHF, FAD286 and spironolactone improve LV haemodynamics, remodelling, and function, but only FAD286 persistently normalizes LV ‘redox status’. These results suggest that aldosterone synthase inhibition is a potential therapeutic strategy for the treatment of CHF.