Search Results (125)

Background: Despite evidence-based guidelines for cardiovascular risk management, many patients fail to achieve therapeutic targets. The relative contribution of medication non-adherence versus suboptimal treatment optimization to poor cardiovascular outcomes remains unclear in real-world primary care settings. The aim of this study was to describe changes in cardiovascular risk factor control following protocolized adherence reinforcement combined with physician-driven treatment optimization in high-risk patients. Methods: This multicenter, real-world longitudinal study included 789 participants with high or very high cardiovascular risk enrolled from primary care settings across 9 Spanish regions between 2023 and 2025. All participants received a protocolized intervention combining adherence reinforcement and physician-driven treatment optimization. This was a single-arm, pre–post study without a concurrent control group; observed changes therefore cannot be attributed to the intervention alone. Of 789 participants screened, all completed the baseline assessment, and 628 (79.6%) completed the 90-day follow-up. A total of 161 participants (20.4%) were lost to follow-up. Primary outcomes included changes in systolic and diastolic blood pressure, lipid parameters (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], triglycerides [TG]), glucose, glycated hemoglobin (HbA1c), and body mass index (BMI) from baseline to 90-day follow-up. Changes were assessed using linear mixed models. Results: Among participants with complete paired data (n = 453–615 depending on the outcome), significant improvements were observed in most cardiovascular risk factors (HDL-c and HbA1c did not change significantly). Mean changes (95% confidence interval [CI]) were: systolic blood pressure, −9.24 mmHg (−10.41 to −8.06; p < 0.001); diastolic blood pressure, −4.75 mmHg (−5.49 to −4.01; p < 0.001); LDL-c, −22.29 mg/dL (−25.59 to −19.00; p < 0.001); TC, −23.24 mg/dL (−26.73 to −19.74; p < 0.001); TG, −16.75 mg/dL (−23.03 to −10.46; p < 0.001); fasting plasma glucose, −10.03 mg/dL (−12.61 to −7.46; p < 0.001); and BMI, −0.46 kg/m² (−0.58 to −0.35; p < 0.001). Linear mixed models including all available data (n = 628 at 90-day follow-up) confirmed these findings. No significant interactions were observed between assessment timepoint and sex, age, or overweight/obesity status for most outcomes, except for age-related differences in lipid responses. Conclusions: Protocolized adherence reinforcement combined with physician-driven treatment optimization was associated with clinically meaningful improvements in multiple cardiovascular risk factors in high-risk primary care patients. Given the single-arm pre–post design, the observed improvements are associative and cannot establish causality. Residual uncontrolled risk, particularly in lipid management and among older adults, persisted despite active treatment optimization (treatment was modified in 82.0% of participants), consistent with residual suboptimal treatment intensification even after adherence had been reinforced. These findings suggest that achieving optimal cardiovascular risk factor control requires addressing both medication adherence and treatment intensification, particularly in patients with multimorbidity. Full article

Background: Dyslipidemia is a modifiable risk factor and predictive biomarker for acute ischemic stroke (AIS) that necessitates early, aggressive lipid-lowering therapy to achieve target low-density lipoprotein cholesterol (LDL-C) levels for primary and secondary prevention. In certain patients, this can be difficult to achieve with statins alone. Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) lipid-lowering agents may improve outcomes when introduced early. This review assessed whether early PCSK9i administration (within 3 weeks of AIS) reduced early neurological deterioration (END), recurrent stroke/transient ischemic attack (TIA), poor functional outcomes, and mortality. Methods: This systematic review and meta-analysis included randomized clinical trials (RCTs) and observational studies. Random-effects meta-analysis and subgroup and sensitivity analyses were used to assess whether effects differed by treatment timing (≤72 vs. >72 h) and study design. Results: Eight studies (three randomized clinical trials) in East Asian cohorts were included. Early PCSK9i initiation significantly reduced END compared with usual care (odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.26–0.57). Stroke/TIA recurrence and all-cause mortality within 6 months of stroke were also significantly reduced in the PCSK9i group (OR: 0.47; 95% CI: 0.28–0.77 and OR: 0.33; 95% CI: 0.15–0.72, respectively), and early initiation was associated with a greater likelihood of good functional outcomes at 90 days (OR: 2.28; 95% CI: 1.48–3.51). Sensitivity analyses yielded consistent results. Conclusions: Early PCSK9i initiation within 3 weeks of AIS onset was associated with lower rates of END, recurrent stroke/TIA, and mortality, although the certainty of evidence was limited by the small number of included studies and the predominantly observational data. Outcomes did not differ significantly by initiation timing within this period. Large-scale trials in diverse populations are needed to define the optimal initiation window and long-term clinical effects. Full article

Background and Aim: Familial hypercholesterolemia (FH) is a genetic disorder leading to severely elevated LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). This study, the GRegistry-FH, provides the first population-based estimation of heterozygous FH (HeFH) prevalence and the clinical profile of affected individuals in Greece. Methods: A cross-sectional, questionnaire-based study was conducted on a representative sample of 7704 adults across 22 Greek regions. HeFH was assessed using the Simon Broome and Dutch Lipid Clinic Network (DLCN) criteria. Clinical characteristics and lipid-lowering therapy (LLT) attainment were compared between individuals with the HeFH phenotype and the general population. Results: The prevalence of HeFH was estimated at 1 in 188 individuals (Simon Broome) and 1 in 183 (DLCN). Individuals with the HeFH phenotype were significantly older and exhibited a much higher prevalence of hypertension (48.8% vs. 23.9%). Notably, individuals with the HeFH phenotype experienced myocardial infarction an average of 14 years earlier than non-FH individuals. Although 80.5% of individuals with the HeFH phenotype were on LLT, only 18.2% achieved LDL-C goals. None of the individuals with the HeFH phenotype with established ASCVD reached the target LDL-C of <1.4 mmol/L (55 mg/dL). Conclusions: HeFH is highly prevalent in Greece but remains largely underdiagnosed in younger ages and suboptimally treated. Despite high treatment rates, the vast majority of individuals with the HeFH phenotype fail to reach protective LDL-C targets. These findings emphasize the need for earlier identification and more aggressive combination lipid-lowering strategies. Full article

Background: Lowering low-density lipoprotein cholesterol (LDL-C) effectively reduces the risk of cardiovascular events. Therefore, we investigated LDL-C levels in geriatric patients undergoing comprehensive inpatient geriatric care. Methods: Patients aged ≥65 years who underwent inpatient comprehensive geriatric care were analyzed. Baseline, clinical, laboratory, and medical data were obtained from case records. For cardiovascular risk stratification, SCORE2, SCORE2-OP, or SMART2 was applied, and LDL-C targets for primary or secondary prevention of atherosclerotic cardiovascular disease (ASCVD) were defined. Factors associated with LDL-C values within guideline-recommended targets in the univariate analysis were entered into a logistic regression model to identify independent predictors. Results: Of 486 patients, 433 (median age 84.0 years; 67.2% female) were included in the final analysis. The majority of patients (371/433; 85.7%) had a very high cardiovascular risk profile. Lipid-lowering therapy (LLT) was identified in 222 patients (51.3%), while 205 patients (47.3%) had received LLT for ≥3 months. In 219 patients (98.7%), LLT was statin-based, either as monotherapy or in combination. The median LDL-C level in the entire cohort was 85 mg/dL (IQR: 63–114 mg/dL), whereas patients receiving LLT had a median LDL-C level of 66 mg/dL (IQR: 52–83 mg/dL). Overall, 193 patients (44.6%) achieved guideline-recommended LDL-C targets; among patients receiving LLT, 61.5% (126/205) were within target range. Intake of ≥5 medications per day was associated with pre-existing LLT (odds ratio: 3.036; 95% CI: 1.081–8.523; p = 0.035). Statin-based LLT was independently associated with achieving LDL-C targets (odds ratio: 3.383; 95% CI: 2.248–5.092; p < 0.001). Conclusions: Most patients did not achieve guideline-recommended LDL-C targets, while only half received lipid-lowering therapy, predominantly statin-based. Current risk assessment tools and approaches to polypharmacy may require adaptation for geriatric patients. Nevertheless, even the simple implementation of statin therapy alone could substantially improve cardiovascular preventive care in a large proportion of untreated older patients. Full article

Background/Objectives: The management of dyslipidaemia in Slovakia has undergone significant changes in recent years, particularly through the relaxation of prescription restrictions for existing medications and the introduction of new innovative molecules. Achieving target levels of LDL cholesterol (LDL-C) plays a key role in preventing the onset and progression of atherosclerosis-related cardiovascular (CV) diseases. The aim of this study was to analyse how these changes have affected the effectiveness of reaching target LDL-C levels in patients at very high CV risk. Methods: This project was conducted as a retrospective analysis of anonymised LDL-C values from 2020 to 2023 using data from a collaborating nationwide laboratory. Patients included were those diagnosed with acute coronary syndrome (ACS), stroke, and, more generally, those with high and very high CV risk. Target LDL-C values were assessed based on the 2019 ESC/EAS guidelines. Results: A total of 363,020 LDL-C test records from 115,950 patients were evaluated over the four-year study period. Among patients diagnosed with ACS, 2.2–5% achieved target LDL-C levels in the respective years of observation 2020–2023. As many as 6.5–7.4% had LDL-C levels ≥ 4.9 mmol/L. For patients with stroke, only 4–6.6% reached target LDL-C levels, while 5.6–6.7% had levels ≥ 4.9 mmol/L. In the group with very high CV risk, only 1.7–3% achieved target levels, and 7.5–8.7% had extremely high LDL-C levels ≥ 4.9 mmol/L. Despite these modest improvements, over 93.4% of patients in the highest-performing subgroup failed to reach the absolute guideline target threshold in 2023. Conclusions: While the lifting of prescription constraints and the introduction of innovative treatments correlates with a doubling of absolute target attainment and a contraction of extreme hypercholesterolemia, overall control remains critically low in Slovakia. Systematic, protocol-driven combination regimens and intensive follow-up are urgently needed. Full article

Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) is a primary therapeutic target in cardiovascular risk assessment. While direct assays are available, LDL-C is frequently estimated using various formulas, whose performance can vary by population and lipid concentration. This study evaluates the analytical agreement and clinical classification performance of four formulas (Spasić–Kotur–Vujović, Friedewald, De Long, and Martin–Hopkins) against directly measured LDL-C. Methods: Lipid profiles from 3935 fasting adult patients were analyzed. LDL-C was directly measured via a homogeneous assay and compared with calculated values using linear regression and Bland–Altman analyses. Analytical bias and classification accuracy were assessed across stratified lipid levels. Results: Among the evaluated equations, the Spasić–Kotur–Vujović formula showed the closest agreement with directly measured LDL-C. It had the lowest mean absolute bias and mean percentage differences across most lipid strata, as well as narrower limits of agreement compared with Friedewald, De Long, and Martin–Hopkins formulas. Although all formulas showed strong correlations with directly measured LDL-C (Pearson’s r correlation coefficient = 0.956–0.958; intraclass correlation coefficient > 0.974), systematic underestimation of LDL-C was observed for all equations and became more pronounced with increasing total cholesterol, LDL-C, triglycerides, and non-high-density lipoprotein cholesterol concentrations. The Spasić–Kotur–Vujović formula achieved the highest overall classification accuracy (70%), followed by De Long (68%), Martin–Hopkins (61%), and Friedewald (58%). Conclusions: Despite strong correlations, clinically relevant differences in bias and classification exist among LDL-C formulas. The Spasić–Kotur–Vujović formula demonstrated superior agreement and accuracy in this population, suggesting it is a more reliable tool for routine laboratory practice. It should be noted that these findings reflect agreement with the specific homogeneous LDL-C assay used on the Alinity c platform (Abbott Laboratories,, Chicago, IL, USA) and may not be directly generalizable to other analytical systems. Full article

Residual cardiovascular risk arises from dysregulated expression of genes encoding apolipoprotein(a) (LPA), apolipoprotein C-III (APOC3), angiopoietin-like gene 3 (ANGPTL3), and proprotein convertase subtilisin/kexin type 9 (PCSK9). RNA-based therapies, small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs) modulate these targets at the post-transcriptional level through RNA interference and RNase H-mediated degradation, respectively. This scoping review maps the molecular mechanisms, target involvement, and pharmacodynamic outcomes of RNA therapies for managing residual cardiovascular risk, with contextual comparison to traditional lipid-lowering agents. A systematic search of PubMed, Embase, Web of Science, and Scopus was performed from 2020 to February 2026. Of the 1088 records identified, 30 studies met the inclusion criteria. RNA therapies have demonstrated potential for engagement, with 80–98% reductions in Lp(a) (pelacarsen, olpasiran, zerlasiran, lepodisiran), 50–80% reductions in triglycerides (olezarsen, plozasiran, volanesorsen), and 36–44% reductions in low-density lipoprotein cholesterol (LDL-C). Mechanistically, siRNAs achieve gene silencing through RISC-mediated mRNA cleavage, with sustained pharmacodynamic effects (3–6 months) because of Argonaute-2 stability, while gapmer ASOs recruit RNase H1 for mRNA degradation. Conjugation with GalNAc allows for hepatocyte-specific delivery with a subcutaneous bioavailability of 70–85%. Safety profiles were favorable, with injection site reactions (4–12%) being the most common adverse event. This analysis maps the emerging molecular landscape of RNA therapies, highlighting their substantial precision for targeting residual cardiovascular risk pathways that cannot be addressed by traditional agents. Full article

Introduction/Objectives: Although contemporary cardiovascular guidelines endorse intensive low-density lipoprotein cholesterol (LDL-C) lowering and advanced lipid biomarkers for refined risk stratification, important gaps in knowledge and implementation persist. This study evaluated clinician familiarity with novel lipid-lowering therapies, approaches to residual cardiovascular risk, confidence in identifying familial hypercholesterolemia (FH), and perceived usefulness of digital decision-support tools. Methods: A multispecialty, cross-sectional online survey (October 2025) of physicians involved in dyslipidemia care was conducted. The questionnaire assessed familiarity, accessibility, and barriers regarding proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, and bempedoic acid; confidence and practice in managing complex populations and residual risk; confidence in detecting FH and expectations for lipoprotein(a) [Lp(a)]; and perceived value of digital decision-support and automated risk alerts. Descriptive statistics and chi-square tests were performed. Results: Ninety-five clinicians completed the survey, with the largest group (41.1%) being general practitioners. Of them, 20.0% reported familiarity with all three novel therapies, and 49.5% reported restricted access due to cost and reimbursement constraints. Overall confidence in managing dyslipidemia in complex populations was moderate. Of note, 31.6% did not routinely assess residual risk after achieving LDL-C targets. Among those who did, imaging-based evaluation of subclinical atherosclerosis was the most frequently selected approach, followed by Lp(a) and triglycerides, hs-CRP, and apoB. Confidence in recognizing FH was modest, and expectations regarding future Lp(a) testing differed across specialties. Most respondents endorsed integrated decision-support tools and automated risk-alert prompts. Conclusions: Implementation gaps persist in dyslipidemia care, while strong receptiveness to digital decision-support highlights an opportunity to align practice more closely with evidence-based recommendations. Full article

Background/Objective: Immunoglobulin G (IgG) N-glycosylation is an important regulator of immune function and systemic inflammation and has been associated with cardiometabolic diseases. However, little is known about how IgG glycosylation changes during the course of acute coronary syndrome (ACS) and whether these alterations relate to lipid-lowering response after the initiation of statin therapy. The primary aim of this study was to investigate IgG N-glycosylation following ACS and evaluate its association with response to atorvastatin therapy defined as baseline LDL cholesterol reduction of ≥50%. Methods: In this prospective cohort study, 79 statin-naïve patients hospitalized for the first episode of ACS and treated with atorvastatin 80 mg daily after percutaneous coronary intervention were followed longitudinally. Plasma samples were collected at admission (acute phase), discharge (subacute phase), and follow-up (chronic phase). A control group of 21 individuals received atorvastatin for primary prevention. IgG was isolated from plasma, and N-glycans were released, fluorescently labeled with 2-aminobenzamide, and analyzed using hydrophilic interaction-based ultra-high-performance liquid chromatography with fluorescence detection. Derived glycan traits were calculated, including agalactosylated (G0), monogalactosylated (G1), digalactosylated (G2), core fucosylated (F), bisected (B), and sialylated (S) glycans. Results: No significant differences in derived IgG glycan traits were observed between ACS patients and controls at baseline or follow-up. Within the ACS group, a longitudinal analysis revealed significant increases in G0 and F and a decrease in G2 between the acute and chronic phases. A total of 65% of patients achieved ≥50% reduction in LDL cholesterol (LDL-C), whereas only 22% reached the guideline-recommended LDL-C target of <1.4 mmol/L. Patients achieving ≥50% LDL-C reduction exhibited consistently higher G0 and lower G2 and S across disease phases. In a subgroup of patients with baseline LDL-C >3.9 mmol/L, those who failed to achieve ≥50% LDL-C reduction had significantly lower G0 and higher S across all time points. Conclusions: Specific glycan traits are associated with the degree of LDL-C reduction achieved during statin therapy, particularly in patients with high baseline LDL-C. These findings suggest that IgG glycosylation patterns may reflect biological phenotypes associated with differential lipid-lowering responsiveness after ACS. Full article

Background/Objectives: The guideline targets for blood pressure (BP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) are frequently unmet, and physicians often misjudge control. This study aimed to characterize the real-world control of BP, HbA1c, and LDL-C in patients with type 2 diabetes (T2D) and hypertension, herein called cardiometabolic multimorbidity (CMM), and to compare guideline-based versus physician-perceived disease control. Methods: We conducted SNAPSHOT–Brazil, a nationwide, multicenter, cross-sectional study to gather real-world data on patients with CMM. The ESC guidelines defined the cardiovascular (CV) risk and control targets. Results: We included 451 patients with hypertension and T2D (median age 65 years; 60% female; 54% White). Most patients (98%) were on pharmacotherapy and reported high adherence (according to the Hill–Bone Medication Adherence Scale). A very high CV risk predominated (78%); 22% of the patients were at a high risk. The guideline-defined control was achieved in 27% for BP, 34% for HbA1c, 13% for LDL-C, and 6% for both BP and LDL-C; only 3% met all three targets simultaneously. The physicians accurately stratified the CV risk in 49% of patients, while 50% had their CV risk underestimated. They systematically overestimated control in 29% of cases for BP, 35% for LDL-C, and 25% for both. The sensitivity ranged from 0.88 to 0.98; the positive predictive values ranged from 0.19 to 0.48, and the positive likelihood ratios ranged from 2.16 to 3.65. Conclusions: The SNAPSHOT–Brazil study revealed a low attainment of BP, HbA1c, and LDL-C targets, despite the widespread pharmacotherapy and the high self-reported adherence. The physicians consistently overestimated disease control and underestimated the CV risk. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Introduction/Objectives: Although contemporary guidelines strongly support intensive low-density lipoprotein cholesterol (LDL-C) lowering and the use of advanced lipid biomarkers for cardiovascular risk stratification, implementation in daily clinical practice remains inconsistent. This study aimed to assess current practices, knowledge, and perceived barriers in dyslipidemia management across medical specialties. Methods: We conducted a cross-sectional, anonymous online survey from August to September 2025 among physicians actively involved in lipid management. The questionnaire evaluated the use of Systematic Coronary Risk Evaluation 2 (SCORE2)-based risk assessment, familiarity with LDL-C targets, treatment intensification strategies, awareness and use of apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)], perceived barriers to LDL-C goal attainment, and responses to a standardized clinical vignette. Descriptive analyses and chi-square testing were conducted. Results: Ninety-five physicians completed the survey, the majority practicing in Europe (92.7%), including 83.2% from Portugal (41.1% general practice/family medicine; 14.7% cardiology; 14.7% internal medicine/geriatrics; 14.7% vascular surgery; 9.5% endocrinology). SCORE2 calculators were used “often” or “always” by 52.6%, with significant inter-specialty variation (p < 0.001). Familiarity with LDL-C targets was high (76.8%), and 89.4% reported frequent therapy intensification when goals were not achieved; however, consistent escalation (“always”) differed markedly across specialties (p < 0.001). Although 69.5% were aware of recommendations for lifetime assessment of apoB/non–HDL-C/Lp(a), only 17.9% implemented them routinely. Most clinicians reported never or rarely using advanced biomarkers for residual risk assessment, and in a clinical vignette only 12.6% would consistently intensify therapy despite elevated Lp(a) and apoB (p = 0.004). Patient non-adherence (86.3%) was the most frequently perceived barrier. Conclusions: Despite the widespread awareness of LDL-C targets, important gaps persist in the consistent application of guideline-directed therapy and in the use of advanced biomarkers. The underutilization of apoB and Lp(a), together with therapeutic inertia and structural barriers, limits effective residual risk management. Bridging this gap will require coordinated efforts focused on implementation, access, and multidisciplinary care. Full article

Background: Patients with type 2 diabetes (T2D) have high morbidity and mortality rates, mainly due to cardiovascular diseases (CVDs). Given the heterogeneity of this population, in whom atherosclerotic CVD may coexist with varying degrees of microvascular and renal involvement, preventive and therapeutic needs differ among these patients. Multifactorial CV risk factor control has proven beneficial in T2D; however, it remains suboptimal, particularly for lipid and weight targets. Aims: The aims were to evaluate, in a real-world cohort of patients with T2D, whether different cardio-reno-microvascular phenotypes are associated with differences in multifactorial cardiometabolic control and to assess individual target attainment along with the use of cardioprotective therapies across phenotypes. Methods: In a single-center, cross-sectional study, 174 patients with T2D were enrolled and clustered into four phenotypes based on the presence of atherosclerotic CVD (ASCVD), chronic kidney disease, retinopathy and neuropathy. Achievement of individual and multifactorial cardiometabolic risk factor control was examined across phenotypes. Results: More than three quarters of the cohort had ASCVD, microvascular/renal disease, or both. While approximately half of the patients had optimal glycemic control, achievement of LDLC and normal BMI was modest. Target attainment did not differ significantly across phenotypes, with most patients achieving one or two targets and less than one third achieving three or more. Statin use was significantly higher in phenotypes with ASCVD, whereas use of other lipid-lowering therapies remained low. Use of SGLT2is and GLP-1 RAs was also limited. Higher BMI was independently associated with lower odds of multifactorial control. Conclusions: In this real-world cohort of patients with T2D, individual and multifactorial cardiometabolic risk factor control was suboptimal, particularly for LDLC and body weight. A phenotype-based approach may help clinicians identify vulnerable subgroups requiring more intensive, risk-based preventive strategies. Full article

Patients with prior acute myocardial infarction (AMI) generally show low rates of achieving secondary prevention targets. Here we evaluated adherence to guideline-recommended secondary prevention strategies after AMI in Saudi Arabia. This ambispective multicenter cohort study included consecutive patients seen for follow-up visits 6–24 months after hospitalization for AMI. A standardized questionnaire was used to evaluate control of blood pressure (<130/80 mmHg), HbA1c (<7%), LDL-C (<1.4 mmol/L), lipoprotein(a) (<50 mg/dL), body mass index (18.5–24.9 kg/m²), physical activity targets, smoking habits, guideline-directed medical therapy (GDMT), and referral to cardiac rehabilitation. Among 108 AMI patients (mean age 58.4 ± 10.9 years; 80.6% male; 76.9% Saudi nationals), 53.7% had uncontrolled blood pressure, ~40% uncontrolled glucose, and 67% above-target LDL-C levels. Most participants were overweight (40.7%) or obese (37%), and 28.7% achieved the physical activity targets. One-third of patients were not receiving all GDMT, 15.7% were current smokers, and 25% had been referred to cardiac rehabilitation. No patient met all guideline-recommended secondary prevention targets. This pilot study highlights gaps in secondary prevention among AMI survivors. Upcoming study phases will aim for national representation and help identify key clinical and demographic drivers to improve secondary prevention efforts across Saudi Arabia. Full article

Therapeutic inertia in lipid-lowering treatment remains a striking paradox of modern cardiovascular medicine: at a time when the causal role of LDL-cholesterol in atherosclerotic disease is unequivocal and potent therapies are widely available, a substantial proportion of high- and very-high-risk patients still fail to receive timely treatment intensification. Contemporary European and international data consistently show fewer than one in three patients in secondary prevention achieve guideline-recommended LDL-C targets, revealing a persistent and unacceptable gap between scientific evidence and clinical reality. This narrative review examines therapeutic inertia as a key explanatory framework for this gap, describing its epidemiology, mechanisms, and clinical consequences in secondary cardiovascular prevention. We summarize the main physician-, patient-, and system-level determinants and propose recurrent clinician “phenotypes” of inertia that may help explain why opportunities are missed even in the highest-risk patients. The consequences are profound: therapeutic inertia contributes to what we propose as the conceptual framework of an “avoidable atherosclerotic burden”, the cumulative vascular injury that accrues each period in which LDL-C remains above target, translating into higher rates of avoidable cardiovascular events, and increased healthcare costs. Emerging strategies such as upfront combination therapy, decision-support systems, structured lipid pathways, and the integration of artificial intelligence offer practical tools to shift lipid management from reactive to proactive care. Overcoming therapeutic inertia is therefore not merely a matter of improving process metrics, but a clinical and ethical imperative. Closing the gap between evidence and practice requires transforming optimal lipid management from an exception into a system-level default, ensuring that every patient receives the full benefit of therapies proven to save lives. This work proposes a novel characterization of clinician ‘phenotypes’ and the concept of ‘avoidable atherosclerotic burden’ as a framework to understand and address this gap. Full article