A novel flow-based parameter of collateral function assessed by intracoronary thermodilution.

BACKGROUND: Currently, many methods for quantitation of coronary collateral function are based on intracoronary pressure measurements distal of an occluded balloon, which do not fully account for the dynamic nature of collateral flow. Therefore, a flow-based parameter of coronary collateral function based upon principles of thermodilution was evaluated. METHODS: In 26 patients with a high-grade coronary artery stenosis, intracoronary hemodynamics were analyzed by the RadiAnalyzer system (St Jude Medical), including fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and the pressure-based collateral flow index (CFI) during balloon occlusion and hyperemia (intravenous adenosine). Moreover, immediately after an intracoronary bolus of room-temperature saline, the balloon was occluded and the intracoronary temperature distal to the balloon was analyzed over time. The slope of the temperature-time curve was calculated after logarithmic transformation as an index of collateral blood flow (CBFI). RESULTS: The coefficient of variation between two measurements of CBFI amounted to 11 ± 2%. In patients with CFI ≥0.25, CBFI amounted to 0.55 ± 0.09, whereas in those with CFI <0.25, CBFI was 0.37 ± 0.03. CBFI correlated significantly with CFI (r = 0.65; P<.001). Interestingly, in the subgroup with IMR below the median (<14.2 mm Hg · s), the slope of the linear regression for CBFI vs CFI was steeper than in individuals with higher IMR, which indicates more effective collateral flow for any given intracoronary pressure distal to the occluded balloon in the group with lower microvascular resistance. CONCLUSIONS: This novel index might be useful as a flow-based index of collateral function, and should be evaluated in further studies.

Efficacy of a minicourse in radiation-reducing techniques in invasive cardiology: a multicenter field study.

OBJECTIVES: Our goal was to validate an educational 90-min minicourse in lower-irradiating cardiac invasive techniques. BACKGROUND: Despite comprehensive radiation safety programs, patient radiation exposure in invasive cardiology remains considerable. METHODS: Before and at a median period of 3.7 months after the minicourse at 32 German cardiac centers, 177 interventionalists consistently documented radiation parameters for 10 coronary angiographies: dose area product (DAP), radiographic and fluoroscopic fractions, fluoroscopy time, and number of radiographic frames and runs. RESULTS: A total of 154 cardiologists attended the minicourse and achieved significant (p < 0.001) decrease in patients' median overall DAP (-48.4%), from baseline 26.5 to 13.7 Gy × cm(2). They reduced fluoroscopy times (-20.8%), radiographic runs (-9.1%), frames/run (-18.6%) and frames (-29.6%), and both radiographic DAP/frame (-27.4%) and fluoroscopic DAP/s (-39.3%), which indicate improved collimation, reduced-irradiation angulations, or adequate image quality. Dose-related parameters for the remaining 23 invited cardiologists unable to attend the workshop did not change significantly in univariate comparison. Multilevel analysis (p < 0.001) confirmed the efficacy of the minicourse itself (-14.7 Gy × cm(2)) and revealed higher DAP for increasing body mass index (+1.5 Gy × cm(2) per kg/m(2)), male sex (+5.8 Gy × cm(2)), age (+1.5 Gy × cm(2)/decade), and-owing to different settings during image acquisition-for advanced flat-panel detector systems (+9.0 Gy × cm(2)) versus older, traditional image intensifier systems. CONCLUSIONS: Despite significant required training in radiation safety for all interventional cardiologists, the presented additional 90-min minicourse significantly reduced patient dose.

Do patients with type 1 and type 2 diabetes really have an impaired endothelial function? A population-based propensity score matching analysis.

BACKGROUND: Previous studies suggested an impaired endothelial function in patients with diabetes. However, the validity of this finding may be limited by the lack of adequate adjustment for further cardiovascular confounders. We assessed endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in patients with either type 1 or type 2 diabetes in comparison with non-diabetic controls. METHODS: The study population comprised 1487 subjects including 122 subjects with type 2 diabetes, aged 25 to 85, from the population-based Study of Health in Pomerania, and 65 outpatients, aged 23 to 75, with type 1 diabetes. FMD measurements were performed using standardized ultrasound techniques. Subjects with type 1 and type 2 diabetes were matched 1:4 to healthy controls using propensity score matching. RESULTS: Neither type 1 diabetes (ß = 0.142; SE = 0.568, p = 0.803) nor type 2 diabetes (ß = 0.107; SE = 0.340, p = 0.752) were significantly associated with FMD in comparison with their non-diabetic controls after adjustment for major cardiovascular confounders like age, gender, body mass index, smoking status, hypertension, antihypertensive medication, LDL and HDL cholesterol levels. CONCLUSIONS: In this population-based study comparing adjusted FMD values of diabetic individuals with adequately matched controls, propensity score analyses revealed no association between diabetes and endothelial function. Since these findings are in discordance with the majority of previous reports, we suggest performing similar analyses using data from other population-based studies.

Association of testosterone levels with endothelial function in men: results from a population-based study.

OBJECTIVE: Because population-based data are lacking, we assessed the cross-sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania. METHODS AND RESULTS: Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04-1.63; P=0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06-1.76; P=0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD. CONCLUSIONS: Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men.

Low serum magnesium concentrations predict cardiovascular and all-cause mortality.

BACKGROUND: Low serum magnesium (Mg(++)) levels are associated with future development of left ventricular hypertrophy independently of common cardiovascular risk factors, as recently demonstrated in the five-year follow-up of the population-based Study of Health in Pomerania (SHIP). As left ventricular hypertrophy has significant prognostic implications, we hypothesized that serum Mg(++) levels are associated with cardiovascular mortality. METHOD AND RESULTS: All-cause mortality and cardiovascular mortality were analyzed in relationship to serum Mg(++) concentrations at baseline by Cox proportional hazard model in SHIP (n=4203, exclusion of subjects with Mg(++) supplementation). The median duration of mortality follow-up was 10.1 years (25th percentile: 9.4 years, 75th percentile: 10.8 years; 38,075 person-years). During the follow-up, 417 deaths occurred. Mortality in subjects with Mg(++)≤0.73 mmol/l was significantly higher for all-cause deaths (10.95 death per 1000 person years), and cardiovascular deaths (3.44 deaths per 1000 person years) in comparison to higher Mg(++) concentrations (1.45 deaths from all-cause per 1000 person years, 1.53 deaths from cardiovascular cause per 1000 person years). This association remained statistically significant after adjustment for multiple cardiovascular risk factors, including arterial hypertension, and antihypertensive therapy including diuretics (log-rank-test p=0.0001 for all-cause mortality, and p=0.0174 for cardiovascular mortality). CONCLUSIONS: Low serum Mg(++) levels are associated with higher all-cause mortality and cardiovascular mortality. This corresponds well with recent findings that hypomagnesemia is associated with the increase of left ventricular mass over the following years.

Comparison of rotational with conventional coronary angiography.

BACKGROUND: Patient radiation exposure and consumption of contrast medium are considered major risks of diagnostic coronary angiography (CA). Rotation of the C-arm during CA could provide similar diagnostic accuracy and lower radiation exposure and contrast medium consumption. METHODS: To compare feasibility, safety, diagnostic accuracy, patient radiation exposure, and consumption of contrast medium of rotational CA with the invasive standard technique, intraindividual comparisons of the results obtained by both techniques were performed in 235 patients with an indication for first-time elective CA. In addition to conventional angiography, we performed 2 isocentric radiographic coronary spins with cranial and caudal tilts by 20 degrees around the left coronary artery and 1 strict posteroanterior rotational spin around the right coronary artery. RESULTS: In 16 patients, rotational CA was not performed because of safety concerns. In a further 12 patients, image quality of rotational scans was considered inadequate. In the remaining 207 patients, both modes of CA were proven suitable for anonymized, separate analysis by 3 independent cardiologists. Intraindividual comparison of both CA modes revealed a high degree of diagnostic agreement (Cohen (K) >0.8 for all cardiologists and for each coronary segment). Contrast medium volume during rotational CA and conventional CA amounted to 31.9 +/- 4.5 mL versus 52.2 +/- 8.0 mL (P < .001) and patient radiation exposure amounted to 5.0 +/- 2.6 Gy × cm(2) versus 11.5 +/- 5.5 Gy × cm(2) (P < .001), respectively. CONCLUSIONS: Rotational CA represents a safe and feasible method in clinical routine. Whereas diagnostic accuracy is similar to the usual conventional mode, consumption of contrast medium and patient radiation exposure are significantly reduced.

Low serum magnesium concentrations predict increase in left ventricular mass over 5 years independently of common cardiovascular risk factors.

OBJECTIVE: Left ventricular hypertrophy (LVH) is a significant predictor of adverse cardiovascular events. Experimental studies suggest a pathophysiological role of magnesium (Mg(2+)) in the development of arterial hypertension and LVH. METHODS: In subjects with complete echocardiographic data from the population-based longitudinal "Study of Health in Pomerania" (n=1 348), the difference in left ventricular mass (LVM) over 5 years (echocardiography) was analyzed in relationship to serum Mg(2+) at baseline. RESULTS: Mg(2+) at baseline (0.790 ± 0.003 mmol/l, mean ± SEM) inversely correlated with the difference in LVM over 5 years (p<0.0001, females: p<0.002, males: p<0.024). In the lowest Mg(2+)-quintile (Mg(2+)<=0.73 mmol/l), LVM (187.4 ± 3.1 g at baseline) increased by 14.9 ± 1.2 g, while in the highest Mg(2+)-quintile (Mg(2+)>=0.85 mmol/l) LVM (186.7 ± 3.4 g at baseline) decreased by -0.5 ± 2.8 g (p<0.0001 between quintiles). By multivariable analysis including several cardiovascular risk factors and antihypertensive treatment, serum Mg(2+) was associated with the increase in LVM at a statistically high significant level (p<0.0001). LVM after 5 years was significantly higher in subjects within the lower Mg(2+)-quintiles. This association remained highly significant after adjustment for several cardiovascular risk factors including arterial hypertension and diabetes mellitus. CONCLUSIONS: Hypomagnesemia is one of the strongest predictors of gain in LVM over the following 5 years.

Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up.

BACKGROUND: Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross-sectional and case-control studies. The aim was to assess whether SCH independently impacts development of LVH over time. METHODS: Of 3300 participants of the population-based Study of Health in Pomerania those with overt hyperthyroidism, hypothyroidism, possible thyroid disease or missing echocardiographic baseline data or follow-up were excluded, resulting in a study population of 1112 individuals (556 women) aged 45-81 years. Echocardiographic left ventricular mass divided by height(2·7) (LVMI(ht)), and LVH(ht) (LVMI(ht) > 44 g/m(2·7) in women and > 48 g/m(2·7) in men) was measured at baseline and after 5-year follow-up (median 5·00; range 4·92; 5·08). Comparison of subjects with (n = 107) and without (n = 1005) SCH were made by linear and logistic regression models adjusted for age, gender, smoking status, hypertension, and waist circumference. RESULTS: At follow-up, LVMI(ht) did not differ between subjects with and without SCH (50·2 g/m(2·7), interquartile range (IQR) 41·2; 59·5 vs 47·8 g/m(2·7), IQR 39·3; 56·9; P = 0·29). LVH(ht) was present in 66 (61·7%) subjects with and 543 (54·0%) persons without SCH (P = 0·13). Analyses revealed no association between SCH and progression of LVMI(ht) (ß = -0·18; 95%-confidence interval (CI) -2·34; -1·99; P = 0·873), and development of LVH(ht) (relative risk 0·86, 95%-CI 0·60; 1·26; P = 0·462), respectively. CONCLUSIONS: In this population-based sample, SCH had no impact on progression of LVMI and development of LVH during 5-year follow-up in subjects aged 45 years or older.

Blood supply of the graft after cellular cardiomyoplasty.

Cellular cardiomyoplasty is under extensive investigation as a potential therapeutic strategy after myocardial infarction, in congestive heart failure and chronic ischemic heart disease. Various cell sources and techniques for transplantation have been studied in animal models of cardiac disease. The initial goal of replacing myocardial scar tissue by vital myocardial cells, integrated into the host, simultaneously beating and contributing to systolic force, has not yet been accomplished. However, most experimental models provided evidence for enhanced vascularization after cell transplantation. In some investigations, neovascularization was also shown to be accompanied by increased myocardial perfusion. Mechanisms by which vascularization occurs have not been fully elucidated: either the transplanted cells provide an angiogenic stimulus, involving various paracrine or hormone-like factors, which induces the formation of a new vasculature or, depending on the source of transplanted cells, the cells incorporate into the vascular network after proliferation and differentiation. This review summarizes research that specifically studied the occurrence, magnitude and mechanisms of enhanced myocardial blood supply after cellular cardiomyoplasty.

Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania.

OBJECTIVE: IGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD). DESIGN: Cross-sectional population-based observational study. METHODS: The study population comprised 1482 subjects (736 women) aged 25-85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low. RESULTS: In males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07-1.51; P=0.008) for decreased FMD for each decrement of IGF1 s.d. after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74-1.05; P=0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12-1.75; P=0.003; females: OR 0.95, CI 0.77-1.16; P=0.595). There was no association between serum IGFBP3 levels and FMD in both sexes. CONCLUSIONS: Low serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.

Mild renal dysfunction as a non-traditional cardiovascular risk factor?-Association of cystatin C-based glomerular filtration rate with flow-mediated vasodilation.

OBJECTIVE: Chronic kidney disease, at least in its advanced stages, can be regarded as a non-traditional cardiovascular risk factor. The purpose of this study was to evaluate whether early stages of renal dysfunction are associated with flow-mediated vasodilatation, as an early marker of the atherosclerotic disease process. METHODS: In 1515 subjects (753 females) from the population-based Study of Health in Pomerania, the relationship between flow-mediated vasodilatation of the brachial artery (cuff occlusion of the forearm for 5 min) and glomerular filtration rate, estimated on the basis of serum cystatin C levels, was analyzed under consideration of various cardiovascular risk factors. RESULTS: Flow-mediated vasodilatation was 5.75 + or - 0.16% in women and 4.29+/-0.12% in men (mean + or - SEM). Glomerular filtration rate amounted to 94.2 + or - 0.7 ml/min/1.73 m(2), with 8.1% subjects with glomerular filtration rate < or = 60 ml/min/1.73 m(2). Flow-mediated vasodilatation significantly correlated with glomerular filtration rate in the entire population (r=0.237, p<0.001), in women (r=0.224, p<0.001) and in men (r=0.168, p<0.001). Adjusting for age and multiple cardiovascular risk factors and also for high-sensitive C-reactive protein levels revealed a significant association of flow-mediated vasodilatation and glomerular filtration rate in women (p=0.01), but not in men, with similar results when the analyses were restricted to individuals with glomerular filtration rate >60 ml/min/1.73 m(2). CONCLUSION: Mild reduction in renal function is associated with alterations in endothelial function in females. Hence, very mild alterations in kidney function may also be regarded as a cardiovascular risk factor at least in women.

Ranolazine: an anti-anginal drug with further therapeutic potential.

Ranolazine is a novel drug approved for the treatment of chronic angina pectoris. In randomized trials, it significantly reduced the frequency of anginal attacks and the need for use of short-acting nitroglycerine. It improved exercise capacity and delayed onset of anginal symptoms or electrocardiographic signs of ischemia during exercise in patients with chronic stable angina. Unlike other drugs used for the treatment of chronic angina, ranolazine has negligible effects on blood pressure and heart rate. A major mechanism believed to contribute to this clinical efficacy is its inhibitory effect on late sodium influx during the cardiac action potential of cardiomyocytes, which is particularly important in ischemic or hypoxic conditions. Ranolazine thereby reduces intracellular sodium and calcium accumulation during ischemia, as shown in various animal research models. In this review we discuss the pharmacological profile of ranolazine and discuss the current and potential future applications in cardiovascular disease for this drug.

Urinary albumin excretion, even within the normal range, predicts an increase in left ventricular mass over the following 5 years.

There is increasing evidence that urinary albumin excretion, even when below the accepted threshold values for normal excretion, may have significant impact on future cardiovascular risks. To further define this, a total of 1086 patients, aged 45 years and older from the population-based, longitudinal 'Study of Health in Pomerania' were evaluated. Patients had echocardiographic analysis at baseline and 5-year follow-up, and were grouped into quartiles according to their baseline urinary albumin-to-creatinine ratio. At baseline, left ventricular mass in the first three quartiles was similar; however, the fourth quartile was significantly elevated and further increased over the 5-year follow-up. In the first quartile, the albumin-to-creatinine ratio and left ventricular mass did not significantly change over 5 years. In the second and third quartiles, the left ventricular mass progressively increased and was significantly correlated with the albumin-to-creatinine ratio. In multivariable analysis, this association was independent of other common cardiovascular risk factors and applicable to both genders. Our study found that the urinary albumin-to-creatinine ratio, even below the current threshold for definition of microalbuminuria, is significantly associated with increased left ventricular mass.

The association of serum testosterone levels and ventricular repolarization.

UNLABELLED: It is assumed that testosterone is an important regulator of gender-related differences in ventricular repolarization. Therefore, our aim was to study whether serum levels of testosterone are associated with QTc, QT and RR interval variation. SETTING: two independent population-based cohort studies. PARTICIPANTS: 445 male participants (> or =55 years) from the Rotterdam study cohort and 1,428 male participants from the study of health in Pomerania (SHIP) with an electrocardiogram who were randomly sampled for assessment of serum testosterone at baseline, after exclusion of participants with testosterone altering drugs, QTc prolonging drugs or dig(it)oxin, left ventricular hypertrophy and left and right bundle branch block. ENDPOINTS: length of the QTc, QT and RR intervals. ANALYSIS: linear regression model, adjusted for the two individual studies and a pooled analysis of both studies. The pooled analysis of the Rotterdam study and SHIP showed that the QTc interval gradually decreased among the tertiles (P value for trend 0.024). The third tertile of serum testosterone was associated with a lower QTc interval compared to the first tertile [-3.4 ms (-6.5; -0.3)]. However, the third tertile of serum testosterone was not associated with a lower QT interval compared to the first tertile [-0.7 ms (-3.1; 1.8)]. The RR interval gradually increased among the tertiles (P value for trend 0.002) and the third tertile of serum testosterone showed an increased RR interval compared to the first tertile [33.5 ms (12.2; 54.8)]. In the pooled analysis of two population-based studies, serum testosterone levels were not associated with the QT interval, which could be due to a lack of power. Lower QTc intervals in men with higher serum testosterone levels could be due to the association of serum testosterone with prolongation of the RR interval.

Heart valve sclerosis predicts all-cause and cardiovascular mortality.

OBJECTIVES: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) might predict future adverse events. We undertook the present study to investigate the association of AVS and MAC with all-cause and cardiovascular mortality. We further studied whether a combined presence of AVS and MAC is more strongly associated with mortality than the single items and sought to disclose possible gender differences in the investigated associations. METHODS: We used data from 2081 participants aged > or =45 years (1063 women) of the Study of Health in Pomerania (SHIP). AVS and MAC were determined echocardiographically, and a heart valve sclerosis score was calculated by summing up the AVS and MAC variables. The median duration of mortality follow-up was 8.6 years (17,162 person-years). RESULTS: There were 528 subjects (25.4%) with isolated AVS, 35 with isolated MAC (1.7%) and 89 with both AVS and MAC (4.3%). A total number of 228 deaths (11.0%) occurred during follow-up, including 133 (21.6%) with AVS and 95 subjects (6.5%) without AVS (incidence rate ratio 3.49, 95% CI 2.77; 4.40, p<0.001). Likewise, mortality rates were higher for subjects with MAC than subjects without MAC (incidence rate ratio 3.79, 95% CI 2.82; 5.02, p<0.001). Multivariable analyses revealed that the associations of AVS and MAC with all-cause and cardiovascular mortality were independent of major confounders and strongest for highest values of the heart valve sclerosis score. AVS-related mortality was more pronounced in women than in men. CONCLUSION: AVS and MAC are associated with all-cause and cardiovascular mortality. The association between AVS and mortality is gender-specific with women with AVS being at a higher mortality risk than men with AVS. The summation of AVS and MAC to a heart valve sclerosis score improves the predictability with respect to mortality.

Intracoronary blood- or bone marrow-derived cell transplantation in patients with ischemic heart disease.

Soon after the first experimental scientific investigations of cell transplantation in various animal models of myocardial infarction and left ventricular dysfunction, a growing number of clinical trials evaluated the effects of intracoronary injection of peripheral blood- or bone marrow-derived cells in patients with myocardial infarction or chronic ischemic heart disease. In most of these trials, changes in parameters of left ventricular remodeling over time, such as left ventricular volumes, ejection fraction or infarct size, were used as trial end points, whereas information on mortality and morbidity after cell transplantation is sparse. Several meta-analyses, each including various sets of studies, estimated that intracoronary cell therapy was associated with small reductions in left ventricular end-systolic volumes and a moderate increase in left ventricular ejection fraction of 2.9-6.1% over time compared with control patients. As most of the clinical trials included a limited number of patients, results vary substantially between different studies. When evaluating whether effects of intracoronary cell transplantation on parameters of left ventricular remodeling may be transferable to meaningful consequences in terms of clinical outcome, the following aspects appear to be imperative. Robust data on mortality and clinical events based on a sufficient number of patients are required. Furthermore, effects of cell therapy must be compared with established therapeutic concepts for the treatment of myocardial infarction, such as reperfusion therapy or pharmacological interventions aiming at favorably influencing the remodeling process. Moreover, the potential effects of cell therapy must be evaluated as treatment options additive to established therapeutic strategies.

Quinaprilat: a review of its pharmacokinetics, pharmacodynamics, toxicological data and clinical application.

BACKGROUND: Quinaprilat is an ACE inhibitor for intravenous use especially in patients with arterial hypertension or chronic heart failure. In contrast to the oral prodrug quinapril, it has not been approved for clinical application. OBJECTIVE: In this review, the pharmacokinetic and pharmacodynamic profile of quinaprilat as well as toxicological data and results of preclinical and clinical studies are summarized. METHODS: In a PubMed search for the terms "quinaprilat" and "quinapril", literature relevant for this review was selected. RESULTS: Quinaprilat is a potent nonsulfhydryl selective ACE inhibitor with a short elimination half-life of 2 - 3 h, but due to slow dissociation from tissue ACE, once daily dosing is sufficient for effective ACE inhibition. Quinaprilat is excreted mainly in urine. In long-term animal studies, quinaprilat was not teratogenic, mutagenic or carcinogenic. However, due to the risk of fetal and neonatal morbidity and death, it should not be administrated in pregnancy. Quinaprilat is characterized by an excellent safety profile; adverse events occur infrequently and are rarely serious. CONCLUSION: Quinaprilat is an attractive ACE inhibitor, which potently inhibits tissue ACE.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.