A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol.

OBJECTIVE: A rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). METHODS AND RESULTS: Twelve common (minor allele frequency > or =0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (P=0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex-, and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations - 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (P=0.0268, P=0.0476, and P=0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex-, and BMI-adjusted LDL-C (SE=0.05, P=0.0038). CONCLUSIONS: Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation.

Randomized controlled trial on the cardioprotective effect of bone marrow cells in patients undergoing coronary bypass graft surgery.

AIMS: This randomized study investigates whether bone marrow cells (BMCs) can reduce ischaemic injury during cardiac surgery. METHODS AND RESULTS: Forty-four elective coronary artery bypass grafting patients were randomized to control group or BMCs group (whereby autologous BMCs were administered with each dose of cardioplegia antegradely into the coronaries). Troponin I and CK-MB were measured during the first 48 h after surgery and were not significantly different between the control and BMCs groups. The role of cardiopulmonary bypass (CPB) on the cardioprotective effects of BMCs was also studied using an in vitro model of stimulated ischaemia and reoxygenation on right atrial appendages obtained from controls either before or 10 min after the initiation of CPB. Bone marrow cells significantly reduced myocardial injury in muscles obtained prior to CPB. This effect was comparable with ischaemic preconditioning (IP), although their combination did not afford additional benefit. However, when muscles were harvested after CPB, myocardial injury in the ischaemic group alone was less, and BMCs or IP did not exert further protection. CONCLUSION: Bone marrow cells did not afford additional benefit when used as an additive to cardioplegia during CPB. However, BMCs offer cardioprotection as potent as IP, when the heart is not subjected to stress, such as CPB, that per se can precondition the myocardium.

Are baroreflex events detected by invasive and non-invasive techniques coincident?

Cardiac baroreceptor sensitivity, a prognostic indicator for a range of diseases, such as myocardial infarction and stroke, may be estimated from spontaneous fluctuations of arterial blood pressure (BP) and heart rate using sequence analysis. We tested the hypothesis that BP values recorded with the non-invasive Finapres device do not always produce sequences coincident with sequences detected from central BP measurements. Finapres recordings of resting BP in the finger, ascending aorta (Millar catheter-tip transducer) and ECG were obtained from 34 patients undergoing coronary angioplasty, including 24 patients treated with betablockers. Coincidence of baroreflex sensitivity (BRS) sequences was expressed by the sensitivity of the Finapres to detect a simultaneously occurring sequence in aortic pressure. The influence of different criteria to detect and accept sequences from beat-to-beat values of systolic BP (SBP) and cardiac interval (RRi) on the Finapres sensitivity was also assessed. The Finapres was able to detect 70.7% of all three beat intra-arterial sequences when the selection criteria was based on the correlation coefficient between SBP and RRi (>0.85), but decreased to 27.5% when the P-value of the linear regression was limited to 0.05. Changing the thresholds for minimum changes in SBP and RRi also had significant effects on sensitivity, as well as in the corresponding values of BRS. Significant differences in BRS were obtained between invasive and non-invasive estimates, but there was no difference between non-invasive estimates calculated from coincident and non-coincident sequences. Non-invasive, compared with intra-arterial estimates of BRS by sequence analysis are not influenced by coincidence of sequences if acceptance of sequences is based on the correlation coefficient criteria (>0.85).

Influence of non-invasive measurements of arterial blood pressure in frequency and time-domain estimates of cardiac baroreflex sensitivity.

OBJECTIVE: To compare estimates of cardiac baroreceptor sensitivity (BRS) obtained by the Finapres device and from the direct measurement of arterial blood pressure (ABP) values from the ascending aorta, using both spectral analysis and sequence analysis. DESIGN: A cohort study of 45 coronary artery disease patients undergoing routine percutaneous coronary procedures. METHODS: Continuous supine recordings of resting ABP in the finger (Finapres), ascending aorta (Millar catheter-tip transducer) and electrocardiogram were obtained. Beat-to-beat values of systolic ABP (Finapres and aortic) and R-R interval were used to estimate the cardiac BRS from spontaneous sequences and by spectral analysis, using the alpha index for the low-frequency band (0.05-0.15 Hz). The influence of beta-blockers on BRS estimates was also investigated. RESULTS: No significant difference was observed between estimates of BRS derived from the Finapres (BRSFIN) and aortic ABP (BRSAO) by the spectral analysis method (Finapres bias 0.30 +/- 2.52 ms/mmHg). For sequence analysis, BRSFIN was significantly higher than BRSAO (7.80 +/- 4.52 versus 6.44 +/- 3.46 ms/mmHg), but the bias (1.36 +/- 3.10 ms/mmHg) was not significantly different from spectral analysis. No significant differences in BRS were found between beta-blocker users (n = 24) and non-users (n = 10) for either the processing method or source of ABP recording. CONCLUSION: Spectral analysis of cardiac BRS showed a better agreement between estimates obtained from the Finapres and aortic ABP.

Transient drifts between Finapres and continuous intra-aortic measurements of blood pressure.

OBJECTIVES: The accuracy of noninvasive measurements of arterial blood pressure (BP), in comparison to intra-arterial recordings, is normally quantified by the bias, which is usually assumed to be a constant parameter. We tested the hypothesis that continuous beat-to-beat differences are not random and aimed to describe the temporal pattern of any transient drifts. METHODS: Forty participants were studied after undergoing elective cardiac catheterization. Continuous recordings of noninvasive finger BP (Finapres), intra-aortic BP (Millar catheter-tip transducer) and electrocardiogram were carried out for two periods of 10 min each. The mean of continuous beat-to-beat differences between the two BP sources was removed for the entire recording (null bias) and any linear trends were also removed. Stochastic properties of the time series of differences were described by the autocorrelation function. The temporal pattern of transient drifts was characterized by the coherent averaging of positive and negative transients, synchronized by their peak/trough values. RESULTS: On average, autocorrelation functions for differences between mean, systolic and diastolic values were significantly greater than zero for at least 24 beats, implying nonrandom differences. For mean BP, the peak value of positive and negative transient drifts were 4.98+/-3.61% and -6.75+/-7.48%, respectively. The average duration of these transients was approximately 20 s. Patients receiving (N=26) and not receiving beta-blockers (N=14) had similar autocorrelation functions indicative of nonrandom differences. The former showed lower peak/trough values in comparison with the latter, but differences were not statistically significant. CONCLUSION: The presence of transient drifts in beat-to-beat differences between finger and aortic BP can lead to erroneous results if biases are calculated using very short segments of data. Clinical and/or research applications using the Finapres, such as dynamic cerebral autoregulation modelling or sequence analysis for assessment of baroreceptor sensitivity can also be corrupted by the presence of nonrandom short-term fluctuations of the difference signal unless results are averaged for multiple segments of data.

Influence of noninvasive peripheral arterial blood pressure measurements on assessment of dynamic cerebral autoregulation.

Assessment of dynamic cerebral autoregulation (CA) requires continuous recording of arterial blood pressure (ABP). In humans, noninvasive ABP recordings with the Finapres device have often been used for this purpose. We compared estimates of dynamic CA derived from Finapres with those from invasive recordings in the aorta. Measurements of finger noninvasive ABP (Finapres), intra-aortic ABP (Millar catheter), surface ECG, transcutaneous CO2, and bilateral cerebral blood flow velocity (CBFV) in the middle cerebral arteries were simultaneously and continuously recorded in 27 patients scheduled for percutaneous coronary interventions. Phase, gain, coherence, and CBFV step response from both the Finapres and intra-arterial catheter were estimated by transfer function analysis. A dynamic autoregulation index (ARI) was also calculated. For both hemispheres, the ARI index and the CBFV step response recovery at 4 s were significantly greater for the Finapres-derived estimates than for the values obtained from aortic pressure. The transfer function gain for frequencies <0.1 Hz was significantly smaller for the Finapres estimates. The phase frequency response was significantly greater for the Finapres estimates at frequencies >0.1 Hz, but not at lower frequencies. The Finapres gives higher values for the efficiency of dynamic CA compared with values derived from aortic pressure measurements, as indicated by biases in the ARI index, CBFV step response, gain, and phase. Despite the significance of these biases, their relatively small amplitude indicates a good level of agreement between indexes of CA derived from the Finapres compared with corresponding estimates obtained from invasive measurements of aortic ABP.