Abstract 5051: Alteration of Atherogenic Lipoproteins by Statin Therapy in Patients With Diabetes in a Large Pooled Clinical Trial Database

Reducing LDL-C to current goals may still leave an excess of atherogenic lipoproteins as reflected in apolipoprotein (Apo) B levels. Apo B provides a measure of atherogenic particles in blood, a predictor of CHD events. Patients with diabetes mellitus (DM) are at increased CHD risk and warrant intensive therapy. Recent joint ADA and ACCF guidelines recommend reducing Apo B to <90 mg/dL in high-risk patients and optionally to <80 mg/dL in those at very high risk. We examined the effect of statin therapy on the relationship between these Apo B targets and LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) in high-risk patients with and without DM. A pooled analysis of data in the rosuvastatin clinical development program was used to identify 12,269 high CHD risk patients who were examined at baseline and after therapy with rosuvastatin, atorvastatin or simvastatin. Apo B was compared with LDL-C and non-HDL-C both at baseline and on therapy using linear regression. At baseline, Apo B target of 90 mg/dL in DM was equivalent to LDL-C of 115 mg/dL and non-HDL-C of 139.8 mg/dL, which was slightly higher than for non-DM (Table ). Achieving Apo B of 90 mg/dL or 80 mg/dL required much more aggressive LDL-C and non-HDL-C goals on statin therapy. Of note, this effect and resultant targets were very similar in DM and non-DM. Achieving with statin therapy Apo B of 90 mg/dL in high-risk patients requires LDL-C target of ~80 mg/dL and non-HDL-C target of ~108 mg/dL. The on-therapy LDL-C target (<70 mg/dL) and non-HDL-C target (<100 mg/dL) for very high risk patients correspond to Apo B target of 80 mg/dL. During statin therapy, Apo B correlated well with LDL-C (R 2 =0.77– 0.81) and very well with non-HDL-C (R 2 =0.88 – 0.90). Non-HDL-C may be a useful surrogate for direct Apo B measurement. High-risk DM and non-DM patients require lower LDL-C and non-HDL-C targets during statin therapy in order to reduce Apo B to the recommended level.

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Abstract 5146: Statin Therapy Alters the Relationship Between Apolipoprotein B and Both LDL-C and Non-HDL-C in High-Risk Patients: Effect of Race and Ethnic Background

Circulation ◽

10.1161/circ.118.suppl_18.s_1151-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Christie M Ballantyne ◽

Stephen J Nicholls ◽

Philip J Barter ◽

Valerie A Cain ◽

Joel S Raichlen

Keyword(s):

High Risk ◽

Statin Therapy ◽

Ethnic Groups ◽

Development Program ◽

Pooled Analysis ◽

Apo B ◽

High Risk Patients ◽

Chd Risk ◽

Risk Patients ◽

The Relationship

Racial and ethnic subgroups are frequently under-represented in clinical trials of statin therapy. Apolipoprotein (Apo) B provides a measure of atherogenic particles in blood, a predictor for coronary heart disease (CHD) events. Reducing LDL-C to current goals may still leave an excess of atherogenic lipoproteins. A study of predominantly Caucasian high-risk patients suggested that statin therapy may alter the relationship between Apo B and commonly measured lipoproteins. Therapeutic responses in non-Caucasians have not been well studied. This study sought to examine the effect of racial and ethnic backgrounds on these relationships. A pooled analysis of data obtained in the rosuvastatin clinical development program was used to identify 12,269 high CHD risk patients of varying race/ethnic descent (Caucasian, African, Asian, and Hispanic Latino). The relationships between Apo B and both LDL-C and non-HDL-C were compared at baseline and after therapy with rosuvastatin, atorvastatin, or simvastatin. At baseline, an Apo B of 90 mg/dL corresponded to an LDL-C of 114.4 mg/dL for blacks and ~109 mg/dL for Asians and Hispanics (Table ). On statin therapy, to reach an Apo B of 90 mg/dL, blacks required an LDL-C of 87.2 mg/dL, while Hispanics required an LDL-C of 78.3 mg/dL. The baseline non-HDL-C that corresponded to an Apo B of 90 mg/dL was highest for Caucasians and lowest for Asians, with almost no differences observed among the ethnic groups on statin therapy. To achieve the Apo B target of 90 mg/dL, statin therapy required 20 –30 mg/dL lower targets for both LDL-C and non-HDL-C. The strong correlation between Apo B and non-HDL-C on statin therapy (R 2 =0.88 to 0.92) suggests that non-HDL-C may be a useful surrogate for Apo B in all high-risk patients. For all race/ethnic groups, in order to achieve an Apo B target of 90 mg/dL with statin therapy, LDL-C and non-HDL-C targets need to be closer to those currently recommended for very high CHD risk.

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Cardiovascular risk assessment in diabetes and pre-diabetes

ESC CardioMed ◽

10.1093/med/9780198784906.003.0216 ◽

2018 ◽

pp. 923-924

Author(s):

Nikolaus Marx

Keyword(s):

Risk Assessment ◽

Cardiovascular Risk ◽

High Risk ◽

Target Organ Damage ◽

Risk Scores ◽

High Risk Patients ◽

Patients With Diabetes ◽

Risk Patients ◽

Artery Disease ◽

Very High

Patients with diabetes exhibit an increased propensity to develop cardiovascular disease with an increased mortality. Early risk assessment, especially for coronary artery disease, is important to initiate therapeutic strategies to reduce cardiovascular risk. This chapter reviews the current literature on risk scores in patients with type 1 and type 2 diabetes and summarizes the role of risk assessment based on biomarkers and different imaging strategies. Current guidelines recommend that patients with diabetes are characterized as high-risk or very high-risk patients. In the presence of target organ damage or other risk factors such as smoking, marked hypercholesterolaemia, or hypertension, patients with diabetes are classified as very high-risk patients while most other people with diabetes are categorized as high-risk patients.

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Mo-P5:330 Statin therapy and achievement of cholesterol goals in slovak high and very high risk patients

Atherosclerosis Supplements ◽

10.1016/s1567-5688(06)80462-9 ◽

2006 ◽

Vol 7 (3) ◽

pp. 118

Author(s):

Z. Krivosikova ◽

M. Gajdos

Keyword(s):

High Risk ◽

Statin Therapy ◽

High Risk Patients ◽

Risk Patients ◽

Very High

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P5327Are we being able to meet current guidelines LDL-cholesterol goals in very high risk patients? How many of them could benefit of PSCK9 inhibition by the FOURIER/ODYSSEY and NICE criteria?

European Heart Journal ◽

10.1093/eurheartj/ehz746.0296 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T El Andere ◽

J A T Soto ◽

I S Moreira ◽

M N Wamser ◽

H C Freitas ◽

...

Keyword(s):

Cardiovascular Risk ◽

High Risk ◽

Statin Therapy ◽

Ldl Cholesterol ◽

Target Range ◽

Pcsk9 Inhibitors ◽

High Risk Patients ◽

Risk Patients ◽

Pcsk9 Inhibition ◽

Very High

Abstract Background/Introduction With increasing evidence of LDL-cholesterol (LDL-c) lowering and a subsequent reduction in cardiovascular events, guidelines of different parts of the world aim for lower LDL-c goals by risk stratification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has been able to reduce up to 60% LDL-c levels, with further reduction in cardiovascular outcomes. Purpose Our aim was to evaluate the proportion of very high risk patients in a tertiary cardiology center that met LDL-c goal of less than 50mg/dL proposed by the Brazilian Society of Cardiology (BSC) guidelines. Furthermore, we assessed the number of patients that were receiving adequate statin intensity therapy and could benefit from PCSK9 inhibition by the FOURIER/ODYSSEY and by the National Institute for Health and Care Excellence (NICE) criteria. Methods We screened 2180 consecutive patients from March, 2018 to February, 2019 for cardiovascular risk factors, cholesterol and glycemic levels, and current medical therapy at use. Patients were stratified by level of risk, and compliance to recommended statin therapy was evaluated. We then analyzed how many of the very high risk patients, that were in use of high intensity statin therapy, met the inclusion LDL-c levels of the FOURIER/ODYSSEY trials (≥70mg/dL) and the NICE recommendations (≥140mg/dL) for the introduction of PCSK9 inhibitors. Results Of the 2180 patients enrolled to our study, 1225 (56.2%) patients were at very high cardiovascular risk level. Of these patients, 136 (11.1%) met LDL-c BSC guideline levels. Using the LDL-c target of 70mg/dL, an additional 320 (26.1%) patients were below target range. When analyzing statin therapy at use, 913 (74,5%) were receiving adequate statin therapy. Of the very high risk patients in adequate statin treatment, 617 (65.9%) by the FOURIER/ODYSSEY criteria and 88 (9.4%) patients by the NICE criteria would benefit from PCSK9 inhibitors. Conclusions With lower LDL-c goals, achievement of optimal LDL-c levels is now a challenge for current clinical practice. Even though many patients are receiving adequate guideline-based statin therapy, difficulty remains in achieving optimal treatment, especially in the higher risk stratum. These patients would benefit from PCSK9 inhibition, being the NICE criteria, a more cost-effective strategy, still applicable in a substantial portion of our patients.

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High risk US adults with untreated hyperlipidaemia in NHANES: estimated reduction in cardiovascular events with statin treatment

European Heart Journal ◽

10.1093/ehjci/ehaa946.2992 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P.P Toth ◽

M.K Palmer

Keyword(s):

High Risk ◽

Statin Therapy ◽

High Intensity ◽

Statin Treatment ◽

Moderate Intensity ◽

High Dose ◽

High Risk Patients ◽

Chd Risk ◽

The Us ◽

Risk Patients

Abstract Introduction Dyslipidemia is widely prevalent. Despite guidelines that recommend statin therapy for high-risk patients, many of these patents are untreated. This gap in care must be urgently closed. Purpose We analyzed data from the National Health and Nutrition Examination Survey (NHANES) in order to: (1) ascertain the number of high-risk individuals with dyslipidaemia not receiving lipid lowering therapy in the United States; and (2) estimate the reduction in acute cardiovascular (CV) events if those individuals were treated with either moderate or high potency statins in order to achieve at minimum a 30% or 50% reduction in LDL-C levels. Methods Data from NHANES participants who had fasting blood serum data available, including lipids, were included in our analysis (n=14,888). Statistical analyses were performed in the R language. Coronary heart disease (CHD) risk was assessed using NCEP ATP III criteria, and participants were categorized as being at high, intermediate, or low CHD risk. Data from seven surveys from 2003–4 to 2015–6 was used and extrapolations to the US adult population (50 states plus the District of Columbia) were performed using the direct method to the US Census 2000 population. Results We identified 1162 adults (age 20–79) who were high-risk and untreated despite being hyperlipidaemic (LDLC ≥100mg/dL). We estimated they represent 12.8 million individuals in the US 2015–16 population. Without lipid modification and hypothecating 10-year risks of CV events in this group of 20, 25, 30, 35 and 40%, respectively, predicted numbers of CV events are 2.6M, 3.2M, 3.9M, 4.5M, and 5.1M. Moderate-intensity statins reduce LDLC by 30–40% and high-intensity statins by 50–60%. Using untreated LDL-C values from all NHANES surveys we calculated predicted absolute reductions in LDL-C would be at least 42 mg/dL if a moderate-intensity statin was used and at least 70 mg/dL if a high-intensity statin was used, with reductions in CV risk of at least 27% and 46%, respectively. In this group of untreated high-risk individuals, predicted numbers of CV events that could be prevented by moderate-intensity statin for 10 years range from at least 0.7M to at least 1.4M, and with high-intensity statin use for 10 years from at least 1.2M to at least 2.3M, depending on the level of untreated risk. With Numbers Needed to Treat (NTT) between 5 and 18, use of statin treatment in this group would be highly beneficial and cost-effective. Conclusions There are a large number of untreated high-risk individuals with dyslipidaemia in the US. Use of moderate and high dose statin therapy in these patients for 10 years would reduce CV risk by at least 27% and 47%, respectively. Among untreated high-risk patients, the NNTs for moderate and high dose statin therapy are 9–18 and 5–11, respectively, depending on 10-year level of CV risk. The quality of life and socioeconomic implications of these estimates are substantial. Funding Acknowledgement Type of funding source: None

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Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients. A Statement from a European Atherosclerosis Society Task Force

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.03.039 ◽

2021 ◽

Author(s):

Maurizio Averna ◽

Maciej Banach ◽

Eric Bruckert ◽

Heinz Drexel ◽

Michel Farnier ◽

...

Keyword(s):

High Risk ◽

Task Force ◽

High Risk Patients ◽

European Atherosclerosis Society ◽

Risk Patients ◽

Practical Guidance ◽

Very High

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Association of infrapopliteal medial arterial calcification with lower-limb amputations in high-risk patients: A systematic review and meta-analysis

Vascular Medicine ◽

10.1177/1358863x20979738 ◽

2020 ◽

pp. 1358863X2097973

Author(s):

Fabrizio Losurdo ◽

Roberto Ferraresi ◽

Alessandro Ucci ◽

Anna Zanetti ◽

Giacomo Clerici ◽

...

Keyword(s):

Risk Factor ◽

High Risk ◽

Lower Limb ◽

Fixed Effects ◽

Meta Analysis ◽

Arterial Calcification ◽

High Risk Patients ◽

Patients With Diabetes ◽

Risk Patients ◽

Medial Arterial Calcification

Medial arterial calcification (MAC) is a known risk factor for cardiovascular morbidity. The association between vascular calcifications and poor outcome in several vascular districts suggest that infrapopliteal MAC could be a risk factor for lower-limb amputation (LLA). This study’s objective is to review the available literature focusing on the association between infrapopliteal MAC and LLA in high-risk patients. The PubMed and Embase databases were systematically searched. We selected original studies reporting the association between infrapopliteal MAC and LLAs in patients with diabetes and/or peripheral artery disease (PAD). Estimates were pooled using either a fixed-effects or a random-effects model meta-analysis. Heterogeneity was evaluated using the Q and I2 statistics. Publication bias was investigated with a funnel plot and Egger test. The trim-and-fill method was designed to estimate the possibly missing studies. Influence analysis was conducted to search studies influencing the final result. Test of moderators was used to compare estimates in good versus non-good-quality studies. Fifteen articles satisfied the selection criteria ( n = 6489; median follow-up: 36 months). MAC was significantly associated with LLAs (pooled adjusted risk ratio (RR): 2.27; 95% CI: 1.89–2.74; I2 = 25.3%, Q-test: p = 0.17). This association was kept in the subgroup of patients with diabetes (RR: 2.37; 95% CI: 1.76–3.20) and patients with PAD (RR: 2.48; 95% CI: 1.72–3.58). The association was maintained if considering as outcome only major amputations (RR: 2.11; 95% CI: 1.46–3.06). Our results show that infrapopliteal MAC is associated with LLAs, thus suggesting MAC as a possible new marker of the at-risk limb.

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