From the editorThe rule of 5 and the rule of 7 in lipid-lowering by statin drugs
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Maximizing Benefits and Minimizing Adverse Effects of Statins
2024, Endocrine PracticeProlonged Moderate-Intensity Exercise Does Not Increase Muscle Injury Markers in Symptomatic or Asymptomatic Statin Users
2023, Journal of the American College of CardiologyStatin use may exacerbate exercise-induced skeletal muscle injury caused by reduced coenzyme Q10 (CoQ10) levels, which are postulated to produce mitochondrial dysfunction.
We determined the effect of prolonged moderate-intensity exercise on markers of muscle injury in statin users with and without statin-associated muscle symptoms. We also examined the association between leukocyte CoQ10 levels and muscle markers, muscle performance, and reported muscle symptoms.
Symptomatic (n = 35; age 62 ± 7 years) and asymptomatic statin users (n = 34; age 66 ± 7 years) and control subjects (n = 31; age 66 ± 5 years) walked 30, 40, or 50 km/d for 4 consecutive days. Muscle injury markers (lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide), muscle performance, and reported muscle symptoms were assessed at baseline and after exercise. Leukocyte CoQ10 was measured at baseline.
All muscle injury markers were comparable at baseline (P > 0.05) and increased following exercise (P < 0.001), with no differences in the magnitude of exercise-induced elevations among groups (P > 0.05). Muscle pain scores were higher at baseline in symptomatic statin users (P < 0.001) and increased similarly in all groups following exercise (P < 0.001). Muscle relaxation time increased more in symptomatic statin users than in control subjects following exercise (P = 0.035). CoQ10 levels did not differ among symptomatic (2.3 nmol/U; IQR: 1.8-2.9 nmol/U), asymptomatic statin users (2.1 nmol/U; IQR: 1.8-2.5 nmol/U), and control subjects (2.1 nmol/U; IQR: 1.8-2.3 nmol/U; P = 0.20), and did not relate to muscle injury markers, fatigue resistance, or reported muscle symptoms.
Statin use and the presence of statin-associated muscle symptoms does not exacerbate exercise-induced muscle injury after moderate exercise. Muscle injury markers were not related to leukocyte CoQ10 levels. (Exercise-induced Muscle Damage in Statin Users; NCT05011643)
Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users
2021, Journal of the American College of CardiologyCitation Excerpt :Statin users could be included if the statin dose or type had been changed within these 3 months. We calculated ‘atorvastatin’ equivalence to standardize the statin dose potency, as 1 atorvastatin equivalent = 5 mg of atorvastatin = rosuvastatin 1.25 mg = simvastatin 10 mg = lovastatin 20 mg = pravastatin 20 mg (13,14). Statin users were considered symptomatic or asymptomatic based on the presence, localization, and onset of muscle cramps, pain, and/or weakness, using the statin myalgia clinical index score (15).
The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations.
This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users.
Symptomatic (n = 16; age 64 ± 4 years) and asymptomatic statin users (n = 16; age 64 ± 4 years) and nonstatin using control subjects (n = 20; age 63 ± 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization.
Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01).
A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346)
Lipid-lowering treatment and low-density lipoprotein cholesterol target achievement in patients with type 2 diabetes and acute coronary syndrome
2020, Archives of Cardiovascular DiseasesPatients with type 2 diabetes mellitus characteristically display an atherogenic lipid profile with high triglyceride concentrations, low high-density lipoprotein cholesterol (HDL-C) concentrations and low-density lipoprotein cholesterol (LDL-C) concentrations not always elevated. It is unclear if patients with diabetes who present with an acute coronary syndrome (ACS) receive different or more-potent lipid-lowering therapy (LLT).
To investigate lipid abnormalities in patients with and without type 2 diabetes hospitalised for an ACS, and use of LLT before admission and 4 months after the event.
Patients were included in the observational DYSIS II study if they were hospitalised for an ACS and had a full lipid profile.
Of 3803 patients, diabetes was documented in 1344 (54.7%). Compared to patients without diabetes, those with diabetes had a lower mean LDL-C (101.2 vs. 112.0 mg/dL; 2.6 vs. 2.9 mmol/L; P < 0.0001), with a greater proportion attaining concentrations < 70 mg/dL (1.8 mmol/L) (23.9% vs. 16.0%; P < 0.0001) and < 55 mg/dL (1.4 mmol/L) (11.3% vs. 7.3%; P < 0.0001), a higher mean triglyceride concentration (139.0 vs. 121.0 mg/dL; 1.6 vs. 1.4 mmol/L; P < 0.0001) and a lower HDL-C concentration. LLT was more commonly given to patients with diabetes (77.5% vs. 58.8%; P < 0.0001); there were no differences in types of therapy prescribed. Four months after hospitalisation, most patients from both groups were being treated with LLT (predominantly statin monotherapy).
Despite the different lipid profiles, the type of LLT prescribed did not vary depending on the presence or absence of type 2 diabetes. There was no difference in LLT in patients with and without diabetes at 4-month follow-up, except for fibrates, which were used in 2% of patients with and 1% of patients without diabetes. Statin monotherapy of intermediate potency was the predominant treatment in both groups.
Les patients avec un diabète de type 2 sont à très haut risque d’événements cardiovasculaires. Ces patients présentent typiquement un profil lipidique athérogène avec des niveaux élevés de triglycérides, de bas niveaux de cholestérol des lipoprotéines de haute densité et un cholestérol des lipoprotéines de basse densité qui n’est pas toujours élevé. Il n’est pas clair si les patients diabétiques se présentant avec un syndrome coronaire aigu reçoivent ou non des traitements hypolipidémiants différents ou plus puissants.
Nous avons cherché à étudier les différences d’anomalies lipidiques chez les patients atteints et sans diabète de type 2 hospitalisés pour un syndrome coronarien aigu, et dans l’utilisation d’un traitement hypolipidémiant avant l’admission et 4 mois après l’événement de syndrome coronarien aigu.
DYSIS II était une étude observationelle et multinationale dans 17 pays. Les sujets étaient inclus s’ils étaient hospitalisés pour un syndrome coronarien aigu et avaient un profil lipidique complet disponible.
Sur les 3803 patients inclus, le diabète de type 2 a été documenté pour 1344 (54,7%) patients. Les patients avec un diabète avaient des niveaux inférieurs de cholestérol des lipoprotéines de basse densité (101,2 vs 112,0 mg/L ; 2,6 vs 2,9 mmol/L ; p < 0,0001) – une proportion plus élevée atteignait un niveau < 70 mg/dL (1,8 mmol/L) (23,9% vs 16,0% ; p < 0,0001) et < 55 mg/dL (1,4 mmol/L) (11,3% vs 7,3% ; p < 0,0001) – le niveau moyen de triglycérides était plus élevé (139 vs 121 mg/dL ; 1,6 vs 1,4 mmol/L ; p < 0,0001) et les niveaux de cholestérol des lipoprotéines de haute densité étaient inférieurs à ceux sans diabète. Le traitement hypolipidémiant était plus fréquemment utilisé par les patients avec du diabète que par ceux sans (77,5% vs 58,8% ; p < 0,0001), mais il n’y avait aucune différence dans les thérapeutiques prescrites. Quatre mois après l’hospitalisation, la majorité des patients des deux groupes étaient traités par un traitement hypolipidémiant : une statine en monothérapie a été utilisée principalement.
Malgré les différents profils lipidiques, le type de traitement hypolipidémiant prescrit ne varie pas en présence ou en l’absence d’un diabète de type 2. Il n’y avait pas de différence de traitement hypolipidémiant chez les patients diabétiques ou non au 4e mois du suivi à l’exception des fibrates qui étaient prescrits chez 2% des patients diabétiques contre 1% chez les patients non diabétiques. La monothérapie par statine d’intensité intermédiaire est la thérapeutique prédominante dans les deux groupes.
Prescribing Statins to Reduce Cardiovascular Disease: 10 Common Misconceptions
2019, American Journal of MedicinePravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1
2019, PlacentaStatins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.
At E14.5, untreated pregnant wild-type (WT, n=13–18), untreated HO-1+/− (Het, n=6–9), and Het mice treated with pravastatin (Het+Pravastatin, n=12–14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.
Compared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0–73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2–5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.
Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.