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Background: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients.
Methods: Patients (n = 605, mean age 56.2 +/- 9.4 years, 82.3% male) with arterial hypertension and cardiac ejection fraction (EF) >= 40% were studied. Cardiac parameters were assessed by echocardiography.
Results: The cohort comprised subjects with coronary heart disease (73.1%) and myocardial infarction (48.1%) with a mean EF of 63.7 +/- 8.9%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4 mm Hg, 95% confidence interval (CI): 0.3 to 4.5 mm Hg, p = 0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8% (CI: 0.45 to 3.14%) in carriers versus non-carriers (p = 0.009).
Conclusion: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.
BackgroundCurrent data on the management of patients in cardiac rehabilitation (CR) after an acute hospital stay due to ST-segment elevation or non-ST segment elevation acute coronary syndromes (STE-ACS or NSTE-ACS) are limited. We aimed to describe patient characteristics, risk factor management, and lipid target achievement of patients in CR in Germany and compare the 2 groups.
HypothesisWith respect to the risk factor pattern and treatment effects during a CR stay, there are important differences between STE-ACS and NSTE-ACS patients.
MethodsComparison of 7950 patients by STE-ACS or NSTE-ACS status in the Transparency Registry to Objectify Guideline-Oriented Risk Factor Management registry (2010) who underwent an inpatient CR period of about 3 weeks.
ResultsSTE-ACS patients compared to NSTE-ACS patients were significantly younger (60.5 vs 64.4 years, P < 0.0001), and had diabetes mellitus, hypertension, or any risk factor (exception: smoking) less often. At discharge, in STE-ACS compared to NSTE-ACS patients, the low-density lipoprotein cholesterol (LDL-C) <100 mg/dL goal was achieved by 75.3% and 76.2%, respectively (LDL-C <70 mg/dL by 27.7% and 27.4%), the high-density lipoprotein cholesterol goal of >50 mg/dL in women and >40 mg/dL in men was achieved by 49.3% and 49.0%, respectively, and the triglycerides goal of <150 mg/dl was achievedby 72.3% and 74.3%, respectively (all comparisons not significant). Mean systolic and diastolic blood pressure were 121/74 and 123/74 mm Hg, respectively (P < 0.0001 systolic, diastolic not significant). The maximum exercise capacity was 110 and 102 W, respectively (P < 0.0001), and the maximum walking distance was 581 and 451 meters, respectively (P value not significant).
ConclusionsPatients with STE-ACS and NSTE-ACS differed moderately in their baseline characteristics. Both groups benefited from the participation in CR, as their lipid profile, blood pressure, and physical fitness improved.
Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 +/- 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% +/- 9.3%. The mean left ventricular mass index (LVMI) was 52.1 +/- 21.2 g/m(2.7) and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.
There is evidence of substantial benefit of cardiac rehabilitation (CR) for patients with low exercise capacity at admission. Nevertheless, some patients are not able to perform an initial exercise stress test (EST). We aimed to describe this group using data of 1094 consecutive patients after a cardiac event (71 +/- 7 years, 78% men) enrolled in nine centres for inpatient CR. We analysed sociodemographic and clinical variables (e.g. cardiovascular risk factors, comorbidities, complications at admission), amount of therapy (e.g. exercise training, nursing care) and the results of the initial and the final 6-min walking test (6MWT) with respect to the application of an EST. Fifteen per cent of patients did not undergo an EST (non-EST group). In multivariable analysis, the probability of obtaining an EST was higher for men [odds ratio (OR) 1.89, P=0.01], a 6MWT (per 10 m, OR 1.07, P<0.01) and lower for patients with diabetes mellitus (OR 0.48, P<0.01), NYHA-class III/IV (OR 0.27, P<0.01), osteoarthritis (OR 0.39, P<0.01) and a longer hospital stay (per 5 days, OR 0.87, P=0.02). The non-EST group received fewer therapy units of exercise training, but more units of nursing care and physiotherapy than the EST group. However, there were no significant differences between both groups in the increase of the 6MWT during CR (123 vs. 108 m, P=0.122). The present study confirms the feasibility of an EST at the start of CR as an indicator of disease severity. Nevertheless, patients without EST benefit from CR even if exercising less. Thus, there is a justified need for individualized, comprehensive and interdisciplinary CR.
This study investigated the incidence of hypertensive target organ damage (TOD), control of cardiovascular risk factors, and the short-term prognosis in hypertensive patients under contemporary guideline-oriented therapy.
A total of 1,377 consecutive patients (mean age 58.2 +/- 9.9 years, 82.2 % male) with arterial hypertension were included in the ESTher (Endorganschaden, Therapie und Verlauf - target organ damage, therapy, and course) registry at 15 rehabilitation clinics within the framework of the National Genome Research Network. Cardiovascular risk factors, medication, comorbidities, and glomerular filtration rate (GFR) were assessed. Left ventricular hypertrophy (LVH), left ventricular mass (LVM), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF) were determined by two-dimensional echocardiography. The mean follow-up was 513 +/- 159 days. Changes in continuous parameters were tested by the t test, changes in discrete characteristics are presented by means of transition tables and tested with the McNemar test.
The mean LVEF was 59.3 +/- 9.9 %, both mean LVM (238.6 +/- 101.5 g) and LVMI (54.0 +/- 23.6 g/m(2.7)) were increased while relative wall thickness (RWT, 0.46 +/- 0.18) indicated the presence of concentric LVH. Of the patients, 10.2 % displayed renal dysfunction (estimated GFR < 60 ml/min/1.73 m(2)). The 1.5-year overall mortality was 1.2 %. Compared with discharge, at follow-up the proportion of patients with blood pressure (BP) values < 140/90 mmHg decreased from 68.7 % to 55.0 % (p < 0.001) and with low-density lipoprotein (LDL) values < 100 mg/dl from 62.6 % to 38.1 % (p < 0.001). At follow-up significantly more patients displayed a GFR value of < 60 ml/min/1.73 m(2) (10.2 % vs. 16.0 %, p < 0.001).
A significant proportion of hypertensive rehabilitation participants displayed TOD including LVH and renal dysfunction. Even after stringent BP reduction, a considerable increase in nephropathy could be found after 18 months.