SA JOURNAL OF DIABETES & VASCULAR DISEASE RESEARCH ARTICLE VOLUME 21 NUMBER 1 • November 2024 27 guideline-recommended LDL-C target of < 1.4 mmol/l was used44 [T2DM + MDD group (10.5%), T2DM – MDD (10.2%), compared to 24% achieved in both groups]. In contrast, Boekholdt et al.45 found that approximately 40% of patients failed to adequately lower their LDL-C levels on highpotency statin therapy, due to inter-individual variation of statin response and possible non-adherence to medication. Doserelated adverse events, inadequate patient education, incorrect statin doses prescribed, and mood issues such as depression are some important factors as to why patients are non-compliant with their medications.46,47 The South African International Cholesterol Management Practice Study48 reported that the low rates of LDL-C goal achievement among private health-insured participants were due to inadequate statin doses prescribed, use of low-potency statins and non-compliance. The American Heart Association guidelines recommend utilising an appropriate statin dose for percentage reduction of LDL-C rather than treatment goals, as well as altering clinicians’ behaviour concerning the treatment of hyperlipidaemia.49 The increased risk of CV events among this group of patients suggests possible medication adjustments, such as switching medication to a different class or dose to achieve guidelinerecommended target LDL-C levels.11 Some patients may even require combination therapy with other classes of lipidlowering therapies (ezetimibe, fibrates, bile acid sequestrants or niacin)49 to sufficiently lower LDL-C levels. The magnitude of the change in LDL-C level in the T2DM groups indicated a level of LDL-C that was 1.2 ± 0.8 mmol/l away from target levels. This clearly indicates that LDL-C targets remain a distinct reminder that a large proportion of the CV risk has not been adequately addressed within the confines of a managed care organisation. Individuals with T2DM must attain glycaemic control, maintain a healthy lifestyle, and manage co-morbid hypertension and hyperlipidaemia. The simultaneous control of all three ABC parameters is seldom achieved in most adults with T2DM.50-52 Only 13% of patients with T2DM + MDD and 7.1% of patients with T2DM – MDD attained comprehensive glycaemic, SBP and LDL-C control (ABC levels) in this study. The composite ABC targets achieved in an Iranian population with T2DM (42%)53 and in the NHANES 2007–2012 was 23.7%.54 Another study conducted in Japan55 showed patients achieved a 28.0% triple ABC goal. In the NHANES survey, patients with T2DM and severe depression were associated with lower rates of ABC goal attainment compared to those with no depression (5.0 vs 25.4%).54 The lower rates of simultaneous control of all three parameters in this study compared to the previous studies may be attributed to the differences in the demographics, the medication regimen, and diabetes management, patient education and depression severity. Regarding the discrete HbA1c, BP and lipid targets56 within a South African tertiary public hospital, the percentage of T2DM patients reaching BP and HbA1c targets were 49.4 and 16.5%, respectively,56 which were lower than in the T2DM + MDD and T2DM – MDD groups in the private sector of our study. However, the lipid targets attained were higher (46.9%)56 compared to the private sector patients in this study (24%). The LDL-C levels attained by patients in the tertiary hospital were lower and can be attributed to better compliance enforced by positive clinical inertia displayed by the clinical staff in the hospital setting.56 Factors affecting BP control were perhaps due to the increasing age, hyperglycaemia and its pathogenic effects on vascular function,57 and the use of angiotensin-converting enzyme inhibitors. On the other hand, in T2DM patients from 20 countries, including Europe and the USA, a pooled target achievement rate of 42.8% (95% CI: 38.1–47.5%) for glycaemic control, 29% (95% CI: 22.9–35.9%) for BP and 49.2% (95% CI: 39.0–59.4%) for LDL-C was reported in a meta-analysis.58 Conversely the present study reflects a better glycaemic (56, 49%) and BP control (75, 75%), and worse LDL-C control (24, 24%) in people with T2DM, with and without MDD, respectively. A major finding in this study was patients in the T2DM + MDD group achieved better ABC control compared to the T2DM – MDD group, yet a higher number of patients in the T2DM + MDD group were admitted for repeated macrovascular events. This may possibly be explained by the presence of a significant residual CV risk not accounted for by lipidlowering therapies. There could be some residual inflammatory risk in patients with low LDL-C levels or pro-inflammatory pathways59,60 that may not be modulated by statins, or even highpotency statins or combined lipid-lowering therapies.61 Furthermore, the present study shows a beneficial link between treatment modalities claimed (statins, metformin and newer hypoglycaemic agents) and HbA1c and LDL-C levels in older patients with T2DM and MDD. Medication claims appeared to be better in older patients, possibly because the elderly are more vigilant of their cardiometabolic indices, as these indices need to be stringently self-managed. The elderly are more aware of their trajectory of a healthier lifestyle and try to reduce their risks and better manage their glycaemic and lipid levels. These findings were supported in middle-aged and older USA adults62 among health maintenance organisation members in the USA63 and Asia.64 Patients with MDD being treated in this managed-care setting showed better compliance and HbA1c control. Screening and treatment of depression in patients with CAD were found to improve the outcomes of CVD,65 alongside the benefits of mood elevation. Similarly, the recognition and monitoring of depression in T2DM are of relevance due to their association with hyperglycaemia, diabetic complications and poor quality of life.66 Patient care in T2DM has an emphasis on blood glucose levels and hence, intake of hypoglycaemic agents to achieve the targeted glycaemic control may be enforced during their medical reviews. Additionally, over the past decade, health technology in T2DM and antidiabetic agents have received much attention, allowing diabetics a range of hypoglycaemic agents to lower blood glucose levels.67-70 This may account for more patients reaching the glycaemic control target. However, the LDL-C targets were not met as patients may not have been aware of the detrimental effects of not complying with their lipid-lowering therapy and the limited choices of lipid-lowering therapy. Elevated serum levels of LDL-C are perhaps the strongest contributor to atherosclerosis in CAD and thromboembolic stroke.71,72 Reduction of LDL-C levels, usually with statins, confers protection. Therefore, a reduction in LDL-C level of 1 mmol/l usually lowers the CV risk by approximately 20%.21 Patients within the managed-care setting of this study needed to be educated on the importance of compliance with lipidlowering therapies in conjunction with their hypoglycaemic, BP and/or antidepressant medications. Association of depressive symptoms with increased risk of macrovascular complications has been reported in several cohort studies.73-75
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