European Journal of Cardiovascular Medicine

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality worldwide, with ischemic stroke representing one of the most severe and debilitating outcomes. Individuals with Type 2 Diabetes Mellitus (T2DM) are particularly vulnerable, facing a two- to four-fold increased risk of stroke compared to non-diabetic individuals. This heightened risk is attributed to a complex interplay of metabolic disturbances, including chronic hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation, all of which contribute to the acceleration of atherosclerosis and the formation of blood clots.

Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein, has emerged as a potential risk factor for atherosclerotic cardiovascular diseases, including ischemic stroke. Despite its recognized role in promoting atherogenesis and thrombosis, the relationship between Lp(a) levels and stroke risk, particularly in patients with T2DM, remains inadequately explored. This study aims to assess the significance of Lp(a) in stroke patients, differentiating between those with and without T2DM, to enhance risk stratification and inform targeted treatment strategies.

Objectives

• To assess the association of Lp(a) levels in ischemic stroke patients with and without T2DM.
• To evaluate the correlation of Lp(a) with various biochemical markers and demographic factors.

Study Design

This research employed a case-control observational study design to assess the association of Lipoprotein(a) levels in ischemic stroke patients with and without Type 2 Diabetes Mellitus (T2DM).

Setting

The study was conducted at Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, Uttar Pradesh, India, over a period from June 2024 to February 2025.

Participants

A total of 122 patients with ischemic stroke were recruited, consisting of 61 patients diagnosed with T2DM and 61 without the condition, ensuring a balanced representation of both groups.

Variables

The primary variable of interest was the serum Lipoprotein(a) level, while secondary variables included demographic characteristics, biochemical markers, and clinical history related to stroke and diabetes.

Data Source/Measurements

Data were collected through structured interviews, medical records, and biochemical measurements, including serum urea, creatinine, liver function tests, HbA1c, and Lp(a) levels, confirmed by MRI for ischemic stroke diagnosis.

Bias

To minimize bias, strict inclusion and exclusion criteria were applied, and random sampling methods were utilized to ensure a representative sample of the population.

Study Size

The sample size was calculated based on the estimated prevalence of elevated Lp(a) levels in T2DM patients with stroke in India, resulting in a required sample size of approximately 120 patients.

Statistical Method

Statistical analysis was performed using SPSS Version 20.0, with continuous variables expressed as means and standard deviations or medians and interquartile ranges, and categorical variables analyzed using Chi-square tests and one-way ANOVA for comparisons. A p-value of less than 0.05 was considered statistically significant.

The study found that the average serum Lp(a) concentration was significantly higher in stroke patients with T2DM (2.51 ± 0.69 g/L) compared to those without T2DM (1.48 ± 0.35 g/L) (p < 0.001). Notably, 75.81% of stroke patients with T2DM exhibited elevated Lp(a) levels (>1.60 g/L), in contrast to 38.34% of non-diabetic stroke patients. Additional biochemical markers, including ALT, AST, and serum triglycerides, also showed significant differences between the two groups.

Table (1): Distribution according to age of the patient in the two groups. (N = 122).

Stroke patients with T2DM were significantly younger (mean 62.09±6.83 years) than non-diabetics (66.14±8.56 years, *p*=0.005). The 51-60 age group had the highest proportion of diabetic strokes (27.86%), while non-diabetic strokes peaked at 66-70 years (27.86%). Only 1.63% of diabetic strokes occurred in ages 71-75 vs. 13.11% in non-diabetics (*p*=0.282 for distribution differences).

Table:(2) Distribution of subjects according to sex in the two groups. (N = 122)

Among 122 stroke patients, males predominated (55.73% overall). In non-diabetic strokes, 57.37% were male vs. 54.09% in diabetic strokes. Females comprised 42.62% (non-diabetic) and 45.9% (diabetic) of cases. No significant sex-based difference was observed (*p* = 0.715).

Table (3): Distribution of subjects according to serum triglycerides in the two groups. (N = 122)

The table shows, by Type 2 diabetes mellitus (DM) presence or absence, the distribution of blood triglyceride levels in stroke victims. Of the stroke patients without Type 2 diabetes, 16 individuals (26.22%) had raised triglycerides (> 150 mg/dL) and 45 individuals (73.77%) had normal blood triglyceride levels (< 150 mg/dL). By comparison, among patients with stroke and Type 2 diabetes, 26 individuals (42.62%) had raised serum triglyceride levels whereas 35 individuals (57.37%) had normal levels. With a p-value of 0.057, the comparison of the two groups shows that there is no statistically significant difference in serum triglyceride levels between stroke patients with and without Type 2 diabetes.

Table (4): Comparison of Lipoprotein(a) levels in case and control group . (N = 122)

T2DM patients had significantly higher mean Lp(a) (2.51±0.69 g/L) vs non-diabetics (1.40±0.35 g/L, p<0.001). High Lp(a) (>1.60 g/L) was more prevalent in T2DM (75.81%) than non-T2DM (38.33%). Only 9.68% of T2DM patients had low Lp(a) (<1.20 g/L) versus 20% in non-T2DM (p=0.001).

Among 122 ischemic stroke patients, those with type 2 diabetes mellitus (T2DM) demonstrated significantly higher mean lipoprotein(a) levels (2.51±0.69 g/L) compared to non-diabetic patients (1.48±0.35 g/L; p<0.001).

The mean age of patients included in this study was 66.14 years with a standard deviation of 8.56 years, indicating that most patients fall within the old-aged bracket.

The 51-60 age group had the highest proportion of diabetic strokes (27.86%), while non-diabetic strokes peaked at 66-70 years (27.86%). Only 1.63% of diabetic strokes occurred in ages 71-75 vs. 13.11% in non-diabetics (*p*=0.282 for distribution differences).The fact that T2DM stroke patients typically are younger fits studies by Kissela et al. (2012)(1), which indicated that diabetes generally results in strokes at an earlier age. This is probably due to diabetes accelerating the development of atherosclerosis and other vascular problems, which increases the risk of strokes in younger people. Likewise, Matsushita et al. (2015)(2) found that those with diabetes not only have a higher risk of stroke but also typically experience it sooner in life than those without diabetes, therefore supporting what we find in Table 1. According to table no. 2, there were 68 male and 54 female patients, representing 55.73% and 44.26% of the total, respectively, suggestive of slight male predominance. 35 males and 26 females were in the stroke without Type 2 DM group, i.e., the control, representing 57.37% and 42.62% of the total control group.There were 33 male and 28 female in the case group, i.e., stroke with Type 2 DM representing 54.09% and 45.9%, respectively, of the total.Men included a somewhat higher number of stroke patients in both groups—with and without T2DM—this is consistent with studies like Appelros et al. (2009)(3), which revealed that men generally have a higher risk of stroke than women, particularly at younger ages. Men's greater rates of smoking, alcohol usage, and cardiovascular risk factors could all help to explain this.

Still, it's interesting that sex distribution among stroke sufferers with and without T2DM does not vary significantly. Studies such as Peters et al. (2014)(4) have indicated that whereas diabetes raises stroke risk for men and women, women may have a somewhat greater relative risk.Table 2's lack of a notable difference could reflect the particular demographic examined or the smaller sample size.Table 4 compares serum triglyceride levels in stroke patients with and without T2DM. Among non-T2DM patients, 26.22% had raised triglycerides (>150 mg/dL) and 73.77% had normal levels (≤150 mg/dL). In the T2DM group, 42.62% had raised levels and 57.37% normal. Despite more raised triglycerides in T2DM patients, the p-value of 0.057 shows no significant statistical difference. These findings align with Sarwar et al. (2007)(5), who linked diabetes with dyslipidemia, particularly high triglycerides, due to insulin resistance. However, the non-significant p-value is surprising given studies like Mooradian et al. (2009)(6), which found diabetics often have elevated triglycerides and higher cardiovascular risk. The result may reflect a small sample size or specific population factors like diet, activity, or medications.Table 4presents the primary outcome: 9.68% of the case group had low Lp(a), vs. 20% in the control. Normal Lp(a) was seen in 14.52% of the case group (9 people) and 41.67% of the control (25 people). High Lp(a) was present in 75.81% of the case group (47 people) vs. 38.34% in the control (23 people). Mean Lp(a) levels were 2.51 g/L in the case group and 1.48 g/L in the control. These findings align with Erqou et al. (2009)(7), who linked high Lp(a) to stroke, especially in T2DM. Kamstrup et al. (2009)(8) also found high Lp(a) linked to stroke and MI, even in non-diabetics, aligning with the 38.34% in the non-T2DM group. Tsimikas et al. (2018)(9) found Lp(a) a stroke and CAD risk in T2DM. Lp(a), structurally like LDL, promotes plaque and carries oxidized phospholipids, worsening inflammation and artery narrowing. Paré et al. (2019)(10) found higher Lp(a) in T2DM with more CV events. Table 4 supports that T2DM worsens Lp(a) effects, as 95.08% had high Lp(a) (>1.60 g/L). Langsted et al. (2018)(11) linked >50 mg/dL Lp(a) to 1.5–2x stroke risk in diabetics. Nordestgaard et al. (2010)(12) showed Lp(a) is a genetic risk, often unaffected by lifestyle, which may explain high Lp(a) in some non-diabetics. Lp(a) also fuels thrombosis and atherosclerosis, key in stroke. Koschinsky et al. (2017)(13) found Lp(a) drives inflammation, endothelial dysfunction, and plaque instability. Table 4’s data align with this, showing T2DM patients may experience more aggressive atherosclerosis. Overall, the data confirm high Lp(a), especially in T2DM, is a major stroke risk factor, highlighting the need for monitoring and targeted Lp(a)-lowering therapies in high-risk groups.

This study highlights the significant association between elevated Lipoprotein(a) [Lp(a)] levels and the incidence of ischemic stroke in patients with Type 2 Diabetes Mellitus (T2DM). The findings indicate that stroke patients with T2DM not only present with higher Lp(a) levels compared to their non-diabetic counterparts but also experience strokes at a younger age. This underscores the critical need for healthcare professionals to consider Lp(a) as a vital biomarker in the risk assessment and management of stroke in diabetic patients.

Given the independent nature of Lp(a) as a risk factor, routine screening for Lp(a) levels in individuals with T2DM is recommended to identify those at heightened risk for stroke. Furthermore, the study advocates for the development and implementation of targeted therapies aimed at reducing Lp(a) levels, which could significantly mitigate stroke risk and improve patient outcomes. Future research should continue to explore the mechanisms linking Lp(a) to stroke and evaluate the effectiveness of Lp(a)-lowering interventions in high-risk populations.

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