Israel Medical Association Journal

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

Background: The introduction of more potent statins such as atorvastatin and rosuvastatin in Israel was accompanied by massive advertising about their superiority.

Objectives: To assess the need for switching therapy from older statins to more potent ones among diabetic patients with uncontrolled hypercholesterolemia.

Methods: Data on all diabetic patients over 30 years old attending two urban clinics were extracted and analyzed. For each patient we checked the last low density lipoprotein-cholesterol measurements for the year 2006, the brand and the dose of cholesterol-lowering medications, prescriptions and actual purchasing over a 4 month period prior to the last LDL-C[1] measurement, and whether treatment changes were necessary to achieve the LDL-C target (100 mg/dl or 70 mg/dl).

Results: The study population comprised 630 patients, age 66.7 ± 12.6 years, of whom 338 (53.6%) were women. Of the 533 (84.6%) patients whose LDL-C was measured in 2006, 45 (8.1%) had levels < 70 mg/dl and 184 (33.3%) had levels of 70 mg/dl < LDL-C < 100 m/dl.  The reasons for LDL-C > 100 mg/dl were patients not prescribed cholesterol-lowering drugs (38.3%), partial compliance (27.2%), and under-dosage of statins (15.4%); only 7.7% needed to switch to a more potent statin. Reasons for LDL-C > 70 mg/dl were patients not prescribed cholesterol-lowering drugs (34.3%), partial compliance (22.0%), and under-dosage of statins (26.6%); only 8.7% needed to switch to a more potent statin.

Conclusions: Only a small minority of diabetic patients with uncontrolled hypercholesterolemia need one of the potent statins as the next treatment step. More emphasis on compliance and dose adjustment is needed to achieve the target LDL-C level.

Epidemiologic data demonstrate a long-linear realationship between low density lipoprotein-cholesterol levels and risk of coronary heart disease.

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: The implementation of treatment guidelines is lacking worldwide.

Objectives: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Methods: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP[1] target level was assessed.

Results: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of <100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA₁C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up.

Conclusion: Follow-up of patients in a specialized clinic enhances the achievement of LDL[2]-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.

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