👤 Roland Zini

Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor, with a growing recognized role in stroke. To investigate the association between Lp(a) levels, large artery atherosclerosis (LAA) TOAST (Trial of ORG 10172 in Acute Stroke Treatment) category, and stroke-related atherosclerosis distribution (extracranial/intracranial) in a single-center retrospective cohort of patients with ischemic stroke. We included all patients with ischemic stroke admitted between March and December 2021 with Lp(a) levels and computed tomography angiography. Multivariable regression assessed the relationship between Lp(a) and LAA, extracranial carotid stenosis, or intracranial atherosclerotic stenosis (ICAS). Predicted probabilities of atherosclerosis location per Lp(a) increment were estimated from a multinomial logistic regression model. We screened 523 patients and included 397 with complete data. The median age was 78 years, and 47% were female. Median Lp(a) was significantly higher in patients with stroke-related atherosclerosis, particularly those with intracranial involvement. Statin use (adjusted β = 15.01, 95% CI: 3.32-26.70, P = .012) and low-density lipoprotein levels (adjusted β = 0.236, 95% CI: 0.09-0.38, P = .002) were independently associated with Lp(a). Lp(a) was significantly associated with LAA (per 10 mg/dL increment: adjusted odds ratio [OR]: 1.08, 95% CI: 1.03-1.14, P = .003; for Lp(a) ≥50 mg/dL vs <50 mg/dL, LAA prevalence was 27% vs 15%, P = .007; adjusted OR: 2.71, 95% CI: 1.47-5.91, P = .001). Lp(a) ≥50 mg/dL was significantly associated with ICAS (adjusted OR: 4.49, 95% CI: 2.41-8.38, P < .001), but not with extracranial carotid stenosis (P = .065). With increasing Lp(a) levels, ICAS showed the steepest increase in predicted probability. Higher Lp(a) values are associated with LAA stroke, particularly ICAS. Lp(a) levels should be included in the stroke workup. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor. Despite its clinical relevance, data on Lp(a) prevalence and impact in Latin America are limited. We aimed to assess the prevalence of elevated Lp(a) and its association with cardiovascular outcomes in a large, multicenter Argentine registry. The GAELp(a) registry included 3000 adults from six Argentine regions. Lp(a) levels were measured using standardized assays; elevated Lp(a) was defined as >50 mg/dL or >125 nmol/L. Clinical, biochemical, and imaging data were collected retrospectively and prospectively. Associations between Lp(a) and major adverse cardiovascular events (MACE) were evaluated with logistic regression in the overall population and stratified by statin use. Elevated Lp(a) was present in 31.4 % of participants, with no sex difference. It was associated with family history of cardiovascular disease, subclinical atherosclerosis, and familial hypercholesterolemia. Patients with elevated Lp(a) had a higher prevalence of coronary artery disease (18.4 % vs. 12.5 %, p < 0.001), peripheral artery disease (4.8 % vs. 2.5 %, p = 0.001), and MACE (21.3 % vs. 14.8 %, p < 0.001). Elevated Lp(a) independently predicted MACE (OR 1.53, 95 % CI: 1.24-1.90, p < 0.001), with stronger associations in statin-naïve individuals (OR 2.18, 95 % CI: 1.17-4.07). ROC analysis showed modest discrimination (AUC 0.57 in nmol/L, 0.59 in mg/dL). Elevated Lp(a) is frequent in Argentina and strongly linked to cardiovascular disease and events. Its predictive value appears greater in statin-naïve patients, highlighting its role as a marker of residual risk. These findings support routine Lp(a) measurement in cardiovascular risk assessment, particularly in regions with high ASCVD burden. Show less

Obesity is a major health issue that impedes the ability of preconditioning and postconditioning to protect the myocardium against infarction secondary to dysregulation of kinase signaling pathways. Moreover, exercise decreases cardiovascular mortality in obese patients but the mechanism remains to be established. Wild-type (WT) and obese (ob/ob) mice were assigned to sedentary conditions or regular treadmill exercise (1h/day, 5 days/7, 4 weeks, 4° slope, 10-30 cm/s) and underwent 30 min of coronary artery occlusion followed by 24h of reperfusion for infarct size measurement. In WT, exercise reduced infarct size by 60% and increased phosphorylation of kinases such as Akt, ERK 1/2, p70S6K, AMPK and GSK3β. Importantly, the level of corresponding phosphatases PTEN, MKP-3 and PP2C was decreased. Calcium concentration inducing the opening of mitochondrial permeability transition pore (mPTP) was increased by exercise. In ob/ob, regular exercise induced a robust cardioprotection by reducing infarct size (-67%), increasing kinase phosphorylation, decreasing phosphatase levels and improving the resistance to mPTP opening. However exercise did not modify hyperglycemia, hypercholesterolemia, hyperinsulinemia, fat mass and body weight in obese mice. In conclusion, regular exercise induces cardioprotection against myocardial infarction despite obesity and restores pro-survival signaling pathways with simultaneous increase in kinase phosphorylations, decreased levels of phosphatases and increased resistance of mPTP opening, independently from improvement in associated co-morbidities. Show less

Ischemic postconditioning (IPCD) significantly reduces infarct size in healthy animals and protects the human heart. Because obesity is a major risk factor of cardiovascular diseases, the effects of IPCD were investigated in 8- to 10-wk-old leptin-deficient obese (ob/ob) mice and compared with wild-type C57BL/6J (WT) mice. All animals underwent 30 min of coronary artery occlusion followed by 24 h of reperfusion associated or not with IPCD (6 cycles of 10-s occlusion, 10-s reperfusion). Additional mice were killed at 10 min of reperfusion for Western blotting. IPCD reduced infarct size by 58% in WT mice (33+/-1% vs. 14+/-3% for control and IPCD, respectively, P<0.05) but failed to induce cardioprotection in ob/ob mice (53+/-4% vs. 56+/-5% for control and IPCD, respectively). In WT mice, IPCD significantly increased the phosphorylation of Akt (+77%), ERK1/2 (+41%), and their common target p70S6K1 (+153% at Thr389 and +57% at Thr421/Ser424). In addition, the phosphorylated AMP-activated protein kinase (AMPK)-to-total AMPK ratio was also increased by IPCD in WT mice (+64%, P<0.05). This was accompanied by decreases in phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MAP kinase phosphatase (MKP)-3, and protein phosphatase (PP)2C levels. In contrast, IPCD failed to increase the phosphorylation state of all these kinases in ob/ob mice, and the level of the three phosphatases was significantly increased. Thus, although IPCD reduces myocardial infarct size in healthy animals, its cardioprotective effect vanishes with obesity. The lack of enhanced phosphorylation by IPCD of Akt, ERK1/2, p70S6K1, and AMPK might partly explain the loss of cardioprotection in this experimental model of obese mice. Show less