Prevalence of elevated lipoprotein(a) in cardiac rehabilitation patients - results from a large-scale multicentre registry in Germany.

BACKGROUND: Lipoprotein(a) (Lp(a)) is an independent risk factor for myocardial infarction and aortic valve stenosis. European guidelines recommend assessing it at least once in a lifetime, particularly in premature atherosclerotic heart disease. METHODS: A non-interventional registry was conducted at MEDIAN rehabilitation facilities in Germany to assess the frequency of Lp(a) testing in referring acute care hospitals and the prevalence of elevated Lp(a) levels in aortic valve stenosis or premature myocardial infarction. All consecutive patients referred after coronary intervention or aortic valve surgery were included in four cohorts: aortic valve intervention (cohort 1), current/previous myocardial infarction at < 60 years of age (cohorts 2a/2b), and myocardial infarction at ≥ 60 years of age (control). RESULTS: The analysis included 3393 patient records (cohort 1, n = 1063; cohort 2a, n = 1351; cohort 2b, n = 381; control, n = 598). Lp(a) had been determined at the referring hospital in 0.19% (cohort 1), 4.96% (cohort 2a), 2.36% (cohort 2b), and 2.01% (control) of patients. Lp(a) levels were > 50 mg/dL or > 125 nmol/L in 28.79% (cohort 1), 29.90% (cohort 2a), and 36.48% (cohort 2b; p < 0.001) compared to 24.25% (control). Family history of premature cardiovascular disease was reported in 13.45% (cohort 1), 38.56% (cohort 2a), and 32.81% (cohort 2b) compared to 17.89% (control; p < 0.05 for each comparison). CONCLUSIONS: Lp(a) had been rarely assessed in acute management of aortic valve stenosis or premature myocardial infarction despite expanding scientific evidence and guideline recommendation. Given the above-average incidence of elevated Lp(a) levels, awareness for Lp(a) has to increase substantially to better identify and manage high-risk patients.

Pulmonary recovery directly after COVID-19 and in Long-COVID.

Permanent impairment in patients after SARS-CoV-2 infection is frequent, but neither pathophysiology nor mechanisms of the so-called Post-COVID-Syndrome (Long-COVID) are well understood. We present data on pulmonary impairment, pulmonary recovery and outcome comparing patients admitted to a specific COVID-19 rehabilitation program directly after COVID-19 infection with patients long after COVID-19 infection. Diagnostic work up included echocardiography, cardiopulmonary exercise testing and pleural sonography. The rehabilitation program included multimodal respiratory therapy, endurance and resistance muscular training, psychological assistance, and educational measures. Patients in both groups showed similar pulmonary problems. Diaphragm dysfunction was common in both groups. Cardiopulmonary exercise testing showed dysfunctional breathing in most patients of both groups. The specific rehabilitation program applied yielded marked improvements with satisfying pulmonary recovery in both groups. Return to work was possible or expected in most patients. In conclusion, directly after COVID-19 infection as well as in long Covid 4-20 months after COVID-19 dysfunctional breathing patterns in cardiopulmonary exercise testing and diaphragm dysfunction on ultrasound are common and need diagnostic awareness and therapy measures. Specialized rehabilitation programs directly after COVID-19 as well as for Long-COVID patients are effective therapeutic options.

[Late neurological consequences of a SARS-CoV-2 infection]. / Neurologische Spätfolgen einer SARS-CoV-2-Infektion.

BACKGROUND: Persistent neurological late symptoms of SARS-CoV-2 infection are common and require regular follow-up treatment. In order to establish uniform therapy concepts, it is necessary to evaluate individual therapeutic approaches for long COVID and post-COVID-19 syndrome. ANAMNESE: A 62-year-old patient was admitted to our rehab clinic for follow-up treatment after severe SARS-CoV-2 infection with neurological symptoms. The initially extensive laboratory and imaging investigation did not reveal any organic cause for the sometimes apoplectiform, complex clinical picture, so that the patient was transferred directly to our rehabilitation clinic in the event of everyday restrictions and rollator dependency. EXAMINATION AND FINDINGS: Clinically, there was a reduced general condition and the mood was depressed. Neurological symptoms were gait ataxia, hand tremor, amnesic aphasia and reduced ability to concentrate. PET / CT showed no evidence of tumor or inflammation. THERAPY AND PROGRESS: A multimodal therapy program consisting of physiotherapy and occupational therapy as well as psychological support was carried out. In addition, off-label therapy with oral glucocorticoids and colchicine was initiated. In the course of the disease, there was a clear reduction in all symptoms with little residual hand tremor. CONCLUSIONS: Whole body and brain FDG PET can be helpful in long COVID and post-COVID-19 syndrome patients with neurological symptoms of unknown origin. These patients benefit from systematic rehabilitation. Glucocorticoids and colchicine appear to accelerate symptom reduction. The rehabilitative therapy should be continued on an outpatient basis.

Determinants of coronary blood flow in humans: quantification by intracoronary Doppler and ultrasound.

The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72 to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product (r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.

Sphingosylphosphorylcholine, a naturally occurring lipid mediator, inhibits human platelet function.

1 The lysophospholipids, lysophosphatidic acid and sphingosine 1-phosphate, have been reported to activate platelets. Here we examined effects of the naturally occurring related sphingosylphosphorylcholine (SPC) on human platelet function. 2 Platelet activation was determined as aggregation, elevation of intracellular Ca(2+) concentrations, surface expression of P-selectin, GP 53, and GP IIb/IIIa neoepitope PAC-1, and of fibrinogen binding to the platelet surface. 3 Platelets were activated by ADP (5 and 20 micro M), the thrombin receptor-activating peptide TRAP-6 (5 and 20 micro M), the thromboxane A(2) mimetic U-46619 (1 micro M) and collagen (20 and 50 micro g ml(-1)) but not by SPC (up to 20 micro M). 4 SPC concentration-dependently (IC(50) approximately 1-10 micro M) inhibited activation of washed human platelets in response to all of the above agonists, with almost complete inhibition occurring at 20 micro M SPC. 5 The SPC stereoisomers, D-erythro SPC and L-threo SPC, exhibited similar concentration-response curves in inhibiting 20 micro M ADP-induced platelet aggregation, suggesting that SPC did not act via specific lysophospholipid receptors. 6 Although SPC slightly activated platelet protein kinase A (as assessed by VASP phosphorylation), this effect could not explain the marked platelet inhibition. Possible protein kinase C inhibition also did not explain the inhibition of platelet activation by SPC. On the other hand, SPC suppressed agonist-induced Ca(2+) mobilization and phospholipase C stimulation. 7 These results indicate that the lysophospholipid SPC is an effective inhibitor of human platelet activation, apparently primarily by uncoupling agonist-activated receptors from their effectors.

Comparison of signalling mechanisms involved in rat mesenteric microvessel contraction by noradrenaline and sphingosylphosphorylcholine.

1 We have compared the signalling mechanisms involved in the pertussis toxin-sensitive and -insensitive contraction of rat isolated mesenteric microvessels elicited by sphingosylphosphorylcholine (SPC) and noradrenaline (NA), respectively. 2 The phospholipase D inhibitor butan-1-ol (0.3%), the store-operated Ca(2+) channel inhibitor SK>F 96,365 (10 microM), the tyrosine kinase inhibitor genistein (10 microM), and the src inhibitor PP2 (10 microM) as well as the negative controls (0.3% butan-2-ol and 10 microM diadzein and PP3) had only little effect against either agonist. 3 Inhibitors of phosphatidylinositol-3-kinase (wortmannin and LY 294,002, 10 microM each) or of mitogen-activated protein kinase kinase (PD 98,059 and U 126, 10 microM each) did not consistently attenuate NA- and SPC-induced contraction as compared to their vehicles or negative controls (LY 303,511 or U 124). 4 The phospholipase C inhibitor U 73,122 (10 microM) markedly inhibited the SPC- and NA-induced contraction (70% and 88% inhibition of the response to the highest NA and SPC concentration, respectively), whereas its negative control U 73,343 (10 microM) caused only less than 30% inhibition. 5 The rho-kinase inhibitors Y 27,632 (10 microM) and fasudil (30 microM) caused a rightward-shift of the NA concentration-response curve by 0.7-0.8 log units and reduced the response to 10 microM SPC by 88% and 83%, respectively. 6 These data suggest that SPC and NA, while acting on different receptors coupling to different G-protein classes, elicit contraction of rat mesenteric microvessels by similar signalling pathways including phospholipase C and rho-kinase.