Extreme-risk category: High prevalence among stable coronary patients and an emerging widening treatment gap in achieving LDL-cholesterol less than 55 mg/dL.

BACKGROUND AND AIMS: The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) proposed a new "extreme-risk" category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised. We aimed to identify the proportion of patients with stable coronary artery disease (CAD), who are at extreme cardiovascular (CV) risk, and explore how achievable is the new LDL-C goal. METHODS: We enrolled 1629 consecutive patients ≤80 years with stable CAD. Fasting lipids were determined and patients having probable or definite heterozygous familial hypercholesterolaemia (HeFH) were identified using the Dutch Lipid Clinic Network algorithm. RESULTS: The prevalence of risk factors/characteristics suggesting an extreme CV risk were as follows: 32% diabetes mellitus, 33% premature CAD and 9.2% HeFH. In total, 895 (55%) patients had at least one of those risk factors/characteristics and formed the extreme CV risk category. Among patients at extreme risk, 87% were on lipid-lowering therapy, of whom 20.3% had LDL-C <70 mg/dL (1.8 mmol/L) and only 5.3% had LDL-C <55 mg/dL. CONCLUSIONS: More than half of all patients with stable CAD are at extreme CV risk and very few (∼5%) achieve LDL-C levels <55 mg/dL. Using maximally-tolerated high-intensity statin combined with ezetimibe, if necessary, is imperative to bridge the treatment gap, while in selected cases the addition of PCSK9 inhibitors will be required.

High levels of lipoprotein (a) and premature acute coronary syndrome.

BACKGROUND AND AIMS: High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS. METHODS: A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures. RESULTS: A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4). CONCLUSIONS: Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years.

Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease.

BACKGROUND: The amyloid beta peptide is the major protein constituent of neuritic plaques in Alzheimer disease and appears to play a central role in vascular inflammation pathophysiology. OBJECTIVES: This study sought to determine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. METHODS: Abeta40 was retrospectively measured in blood samples collected from 3 independent prospective cohorts and 2 case-control cohorts (total N = 1,464). Major adverse cardiac events (MACE) were assessed in the 2 prospective cohorts (n = 877) followed for a median of 4.4 years. To look at effects on subclinical disease, arterial stiffness was evaluated at baseline and after 5-year follow-up (n = 107) in young healthy subjects. The primary endpoint was the predictive value of Abeta40 for CV mortality and outcomes in patients with CHD. RESULTS: In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein, and high-sensitivity troponin T, Abeta40 independently predicted CV death and MACE in patients with CHD (p < 0.05 for all). After multivariate adjustment, Abeta40 levels conferred a substantial enhancement of net reclassification index and integrated discrimination improvement of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Abeta40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis, and incident CHD. CONCLUSIONS: Measuring blood levels of Abeta40 identified patients at high risk for CV death.

Attainment of optional low-density lipoprotein cholesterol goal of less than 70 mg/dl and impact on prognosis of very high risk stable coronary patients: a 3-year follow-up.

OBJECTIVES: We aimed to investigate the proportion of very high-risk patients with coronary heart disease (CHD) who achieve the optional low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dl (1.8 mmol/liter), the factors that influence the success rate and the impact on their prognosis. RESEARCH DESIGN AND METHODS: We enrolled 1337 consecutive patients with stable CHD. Fasting lipids were determined and all cardiovascular events were recorded during a median follow-up of 33 months. RESULTS: The majority (86.5%) of patients were taking lipid-lowering medication (95.5% statins), but only 50.6% had LDL-C levels of <100 mg/dl (2.6 mmol/liter). In total, 941 (70.4%) patients were considered very high risk and only 15.1% of them had LDL-C levels of <70 mg/dl. Τhe use of intensive lipid-lowering medication was associated with 12-fold (95% CI 6.98-20.76; p<0.001) higher possibility in achieving LDL-C levels of < 70 mg/dl. Attainment of LDL-C levels of < 70 mg/dl by patients at very high risk were independent predictors of all cardiovascular events (HR=0.34, 95% CI 0.17-0.70; p=0.003). CONCLUSIONS: The vast majority of very high-risk patients do not achieve the optional LDL-C goal; this is mainly due to the suboptimal uptitration of statin dose and is translated into loss of clinical benefits.

Mild depression versus C-reactive protein as a predictor of cardiovascular death: a three year follow-up of patients with stable coronary artery disease.

OBJECTIVE: Depression is common in patients with coronary artery disease (CAD) and is associated with higher risk of cardiovascular adverse events. We aimed to explore the prognostic role of mild depression on cardiovascular mortality and compare its prognostic value with C-reactive protein (CRP) levels in patients with stable CAD. RESEARCH DESIGN AND METHODS: We initially recruited 523 consecutive patients with stable CAD. Glucose, lipids and CRP levels were measured and an echocardiographic study was performed. In addition, depressive symptomatology was assessed with the Zung Depression Rating Scale (ZDRS, range 20-80). Patients on antidepressant treatment or with ZDRS score ≥60 were excluded. Patients were followed up at 6 month intervals (median 33 months, interquartile range 24-40 months) by telephone interview. RESULTS: Follow-up data were obtained from 485 patients (92.7%). Nineteen patients with baseline CRP levels >10 mg/L and eight with non-cardiovascular death were excluded from analysis. Of the remaining 458 patients 113 (24.7%) presented cardiac events. Of them 21 died (4.6%), 42 developed acute coronary syndrome (9.2%), 27 (5.9%) had a revascularization procedure due clinical deterioration, two had a stroke (0.44%) and 21 (4.6%) an arrhythmic event. Multivariate Cox regression analysis showed that ZDRS score was independent predictor of cardiovascular death (hazard ratio [HR]: 1.104 with 95% confidence interval [CI]: 1.039-1.172, p = 0.001) after adjustment for conventional risk factors and CRP. The Wald test statistic of CRP was 2.59, whereas the Wald test statistic of ZDRS score was 3.23, indicating better predictability of ZDRS score. ZDRS score was also independent predictor of both cardiovascular death and arrhythmic event (HR: 1.102 with 95% CI: 1.051-1.156, p < 0.001) after adjustment for conventional risk factors and CRP levels. The main limitations of our study were the evaluation of depression at one point in time and the assessment of inflammatory burden by measuring only CRP levels. CONCLUSIONS: Mild depression is associated with increased cardiovascular mortality and is a better predictor than CRP levels in patients with stable CAD.

Lack of association of angiotensin-converting enzyme insertion/deletion polymorphism and myocardial infarction at very young ages.

We examined whether angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism is associated with the development of myocardial infarction (MI) at < or = 35 years of age. The study sample consisted of 201 patients with premature MI and 140 age- and sex-matched healthy individuals. No difference was found in the distribution of ACE genotypes between the patients and controls. A higher prevalence of the DD genotype among hypertensives was found compared with the non-hypertensive patients (62.5% vs 35.6%, p = 0.01). ACE polymorphism is not associated with the development of premature MI and this might be due to the low prevalence of hypertension in young coronary patients.