Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook.

Dyslipidemia refers to unhealthy changes in blood lipid composition and is a risk factor for atherosclerotic cardiovascular diseases (ASCVD). Usually, low-density lipoprotein-cholesterol (LDL-C) is the primary goal for dyslipidemia management. However, non-high-density lipoprotein cholesterol (non-HDL-C) has gained attention as an alternative, reliable goal. It encompasses all plasma lipoproteins like LDL, triglyceride-rich lipoproteins (TRL), TRL-remnants, and lipoprotein a [Lp(a)] except high-density lipoproteins (HDL). In addition to LDL-C, several other constituents of non-HDL-C have been reported to be atherogenic, aiding the pathophysiology of atherosclerosis. They are acknowledged as contributors to residual ASCVD risk that exists in patients on statin therapy with controlled LDL-C levels. Therefore, non-HDL-C is now considered an independent risk factor or predictor for CVD. The popularity of non-HDL-C is attributed to its ease of estimation and non-dependency on fasting status. It is also better at predicting ASCVD risk in patients on statin therapy, and/or in those with obesity, diabetes, and metabolic disorders. In addition, large follow-up studies have reported that individuals with higher baseline non-HDL-C at a younger age (<45 years) were more prone to adverse CVD events at an older age, suggesting a predictive ability of non-HDL-C over the long term. Consequently, non-HDL-C is recommended as a secondary goal for dyslipidemia management by most international guidelines. Intriguingly, geographical patterns in recent epidemiological studies showed remarkably high non-HDL-C attributable mortality in high-risk countries. This review highlights the independent role of non-HDL-C in ASCVD pathogenesis and prognosis. In addition, the need for a country-specific approach to dyslipidemia management at the community/population level is discussed. Overall, non-HDL-C can become a co-primary or primary goal in dyslipidemia management.

Effect of eprosartan-based antihypertensive therapy on coronary heart disease risk assessed by Framingham methodology in Canadian patients with diabetes: results of the POWER survey.

OBJECTIVE: As part of the Physicians' Observational Work on Patient Education According to their Vascular Risk (POWER) survey, we used Framingham methodology to examine the effect of an eprosartan-based regimen on total coronary heart disease (CHD) risk in diabetic patients recruited in Canada. METHODS: Patients with new or uncontrolled hypertension (sitting systolic blood pressure [SBP] >140 mmHg with diastolic blood pressure <110 mmHg) were identified at 335 Canadian primary care practices. Initial treatment consisted of eprosartan 600 mg/day, which was later supplemented with other antihypertensives as required. Outcomes included change in SBP at 6 months (primary objective) and absolute change in the Framingham 10-year CHD risk score (secondary objective). RESULTS: We identified an intention-to-treat diabetes population of 195 patients. Most diabetic patients were prescribed two or more antihypertensive drugs throughout the survey. Mean reductions in SBP and diastolic blood pressure were 20.8±14.8 mmHg and 9.5±10.7 mmHg, respectively. The overall absolute mean 10-year CHD risk, calculated using Framingham formulae, declined by 2.9±3.5 points (n=49). Average baseline risk was higher in men than women (14.8±8.6 versus 5.6±1.8 points); men also had a larger average risk reduction (4.2±4.3 versus 1.5±1.3 points). The extent of absolute risk reduction also increased with increasing age (trend not statistically significant). CONCLUSION: Eprosartan-based therapy substantially reduced arterial blood pressure in our subset of diabetic patients; while there was a slight reduction in Framingham risk, there are indications from our data that both blood pressure control and the wider management of CHD risk in diabetic patients remains suboptimal in Canadian primary care.

Effect of eprosartan-based therapy on systolic blood pressure and total cardiovascular risk in a large international population: preliminary report of the observational POWER study.

BACKGROUND: Estimation of total cardiovascular risk is useful for developing preventive strategies for individual patients. The POWER (Physicians' Observational Work on Patient Education According to their Vascular Risk) survey, a 6-month, open-label, multinational, post-marketing observational evaluation of eprosartan, an angiotensin II receptor blocker, was undertaken to assess the efficacy and safety of eprosartan-based therapy in the treatment of high arterial blood pressure in a large population recruited from 16 countries with varying degrees of baseline cardiovascular risk, and the effect of eprosartan-based therapy on total cardiovascular risk, as represented by the SCORE (Systematic Coronary Risk Assessment) or Framingham risk equations. METHODS: Participating physicians recruited > 29,000 hypertensive patients whom they considered to be candidates (according to specified criteria) for treatment with eprosartan 600 mg/day, with other drugs added at the discretion of the physician. RESULTS: During treatment, systolic blood pressure decreased by 25.8 ± 14.4 mmHg to 134.6 ± 11.4 mmHg (P < 0.001), mean diastolic blood pressure fell by 12.6 ± 9.5 mmHg to 81.1 ± 7.6 mmHg, and pulse pressure fell by 13.2 ± 13.5 mmHg to 53.6 ± 11.4 mmHg (both P < 0.01). Calculated total cardiovascular risk declined in parallel with the reduction in blood pressure. CONCLUSION: The POWER study has demonstrated, in a large and nonselected population, the feasibility and practicability of reducing total cardiovascular risk through systematic management of high blood pressure.

Blood pressure responses to hypertension treatment and trends in cognitive function in patients with initially difficult-to-treat hypertension: a retrospective subgroup analysis of the Observational Study on Cognitive Function and SBP Reduction (OSCAR) study.

The Observational Study on Cognitive Function and SBP Reduction (OSCAR) provided opportunities to examine the influence of eprosartan on trends in cognitive performance in a large population of patients with difficult-to-treat hypertension (DTTH). A total of 4649 patients diagnosed retrospectively with DTTH, defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg despite use of at least 3 antihypertensive drugs during the month preceding the baseline visit comprised the intention-to-treat (ITT) cohort. The patients were given eprosartan-based antihypertension therapy (EBT; 600 mg/d). Blood pressure and cognitive function parameters included significant (P<.001) differences for DTTH vs non-DTTH patients such as older age, body mass index, SBP and pulse pressure (PP), and lower Mini-Mental State Examination (MMSE) score. After EBT for 6 months, SBP/DBP in DTTH was 138.8±12.2/81.9±7.4 (ΔSBP-26±15.7; ΔDBP-11.4±9.8); PP was 57.0±10.8 (ΔPP-14.5±13.8) (all P<.001 vs baseline and non-DTTH group). A total of 2576 patients (87.4%) responded to EBT (ie, SBP <140 mm Hg and/or ΔSBP ≥15 mm Hg, or DBP <90 mm Hg and/or ΔDBP ≥10 mm Hg); 1426 DTTH patients (48.4%) achieved normalized SBP/DBP (ie, SBP <140 mm Hg and DBP <90 mm Hg). ΔPP in DTTH-isolated systolic hypertension (ISH) was -18.0±13.3 mm Hg (P=.003 vs DTTH-systolic-diastolic hypertension). End-of-EBT mean MMSE was 27.5±3.0 (P<.001 vs baseline). Blood pressure responses after EBT coincided with stabilization/improvement of MMSE in this retrospective investigation in DTTH patients. The average improvement in MMSE in DTTH patients was similar to that in non-DTTH patients. EBT effects on PP may be relevant to the evolution of MMSE in DTTH-ISH patients.

Eprosartan-based hypertension therapy, systolic arterial blood pressure and cognitive function: analysis of Middle East data from the OSCAR study.

BACKGROUND: Studies have indicated a relationship between hypertension and cognitive function. The possible effect of antihypertensive therapy on cognitive disorders is therefore a matter of interest. MATERIALS AND METHODS: The Observational Study on Cognitive function And SBP Reduction (OSCAR) was an open-label, multinational trial designed to evaluate the impact of eprosartan-based antihypertensive therapy on cognitive function in patients with essential hypertension. Eprosartan 600 mg/day for 6 months (with provision for additional medication as needed) was initiated in hypertensive subjects aged ≥ 50 years. A total of 853 patients in an intention-to-treat cohort from seven countries of the Middle East was identified for subgroup analysis. RESULTS: Arterial blood pressure was reduced significantly (P < 0.001) during the study: At the end of 6 months of eprosartan-based therapy, the mean (±SD) reduction from baseline was 32.1 ± 14.3/14.6.3 ± 8.6 mmHg (P < 0.001). Mean pulse pressure was reduced by 18.3 ± 13.1 mmHg (P < 0.0001 vs baseline). Blood pressure was normalized (systolic <140 mmHg and diastolic <90 mmHg) in 68.2% of patients. The overall mean Mini-Mental State Examination (MMSE) score after 6 months of eprosartan-based therapy was one-point higher than at baseline (P < 0.001). MMSE score on completion of 6 months' follow-up was either unchanged or increased from baseline in 793 (93%) individuals and decreased in 60 (7%). Factors associated with stability of or improvement in cognitive function included MMSE score at baseline, diastolic blood pressure (DBP) at baseline, and treatment-induced change in DBP. CONCLUSION: Results from the Middle East subgroup of OSCAR are supportive of the hypothesis that antihypertensive therapy based on angiotensin-receptor blocker therapy with eprosartan may be associated with preservation or improvement of cognitive function.

Effects of hypertension therapy based on eprosartan on systolic arterial blood pressure and cognitive function: primary results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction open-label study.

BACKGROUND: Recent studies have indicated a relationship between hypertension and cognitive function but therapeutic trials of antihypertensive therapy on the prevention of cognitive disorders have produced controversial findings. METHODS: The Observational Study on Cognitive function And Systolic Blood Pressure Reduction is an open-label trial in 28 countries designed to evaluate the impact of eprosartan-based therapy on cognitive function. The Mini-Mental State Examination was used as a global tool for the comprehensive assessment of cognitive function, with an intention to treat a cohort of 25 745 hypertensive patients aged at least 50 years during a follow-up interval of 6 months. Blood pressure therapy was initiated with eprosartan 600 mg/day with provision for additional medication to be introduced after 1 month in patients with insufficient blood pressure response. RESULTS: Use of eprosartan, either as monotherapy or in combination regimens, was associated with a substantial reduction in arterial blood pressure from 161.9/93.1 mmHg at baseline to 136.1/80.8 mmHg at 6 months (P < 0.0001). The overall mean Mini-Mental State Examination score at completion of follow-up was 27.9 +/- 2.9 compared with 27.1 +/- 3.4 at baseline (P < 0.0001). A significant correlation was shown between the mean absolute response of Mini-Mental State Examination and the magnitude of systolic blood pressure reduction. At the end of the study, patients with systolic blood pressure less than 140 mmHg had a larger improvement in Mini-Mental State Examination [0.88 +/- 0.01 (SEM)] than those with systolic blood pressure between 140 and 159 mmHg [0.69 +/- 0.02 (SEM); P < 0.001], or than those with systolic blood pressure of at least 160 mmHg [0.38 +/- 0.05 (SEM); P < 0.0001]. Furthermore, cognitive decline was demonstrated in multiple linear regression to be independently associated with age [odds ratio 1.19 (1.14; 1.25)], Mini-Mental State Examination at baseline [odds ratio 1.19 (1.14; 1.25)], systolic blood pressure at baseline [odds ratio 1.20 (1.13; 1.27)] and systolic blood pressure reduction [odds ratio 0.77 (0.73; 0.82)]. CONCLUSION: The results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction are supportive of the proposition that antihypertensive therapy based on drugs that target the renin-angiotensin system is associated with preservation of cognitive function.

A novel approach to treatment of hypertension in diabetic patients - a multicenter, double-blind, randomized study comparing the efficacy of combination therapy of Eprosartan versus Ramipril with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with hypertension and associated diabetes mellitus type 2 - rationale and design [ISRCTN55725285].

Hypertension and diabetes mellitus are closely interrelated and coexist in as many as two-thirds of patients with type 2 diabetes. The consequent risk of such an association is an accelerated development of atherosclerotic cardiovascular disease and nephropathy complications.In choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and nephroprotective properties. Given the multifactorial nature of hypertension, the approach that has gained widespread agreement is treatment with more than one agent. Agents with different mechanisms of action increase antihypertensive efficacy because of synergistic impacts on the cardiovascular system. Combination therapy allows the use of lower doses of each antihypertensive agent which accounts for the excellent tolerability of combination products.The aim of the present study is to quantify the efficacy of combination therapy of Eprosartan 600 mg respectively Ramipril 5 mg with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with essential hypertension and associated diabetes mellitus type 2.The use of monotherapy (Eprosartan or Ramipril) followed by addition of low-dose Hydrochlorothiazide as second agent and of Moxonidine as a third agent will be individualized to the severity of hypertension in the particular patient and to his/her degree of response to current treatment.