Relationship of Microalbuminuria with Ischemic Heart Disease in Nondiabetic Subjects

Abstract

Background:

Microalbuminuria has been established as a marker for increased cardiovascular risk in diabetic patients. Nonetheless, its correlation with ischemic heart disease (IHD) among individuals without diabetes has received limited attention. The current study was performed to explore the potential link between microalbuminuria and IHD in nondiabetic subjects.

Methodology:

During 2 years, a case–control study was executed, encompassing 100 individuals without diabetes who had IHD as cases, and an equal number of 100 non-IHD controls. Microalbuminuria levels were evaluated alongside diverse cardiovascular risk factors in both sets. IBM-SPSS version 25.0 was used for statistical analysis.

Results:

The mean age, gender distribution, and body mass index were similar between the cases and controls. There was a higher prevalence of smokers and alcohol users among the cases compared to controls. In addition, a positive family history of IHD was more prevalent in the case group. In the case group, the mean values of systolic blood pressure, diastolic blood pressure, mean arterial pressure, fasting blood glucose, cholesterol, low-density lipoprotein (LDL), serum creatinine, and urine albumin levels were notably elevated compared to the control group. A significant increase in microalbuminuria levels in the case group was observed.

Conclusion:

The results reveal a substantial link between microalbuminuria and IHD in individuals without diabetes. Microalbuminuria was independently correlated with major cardiovascular risk factors, including alcohol and cigarette use, and higher levels of cholesterol, LDL, and serum creatinine. These findings suggest that urine albumin measurements could serve as an early marker for identifying cardiovascular disease risk factors and potentially aid in preventive interventions in the general population.

INTRODUCTION

Ischemic heart disease (IHD) holds the position of being the foremost cause of mortality in India, contributing to approximately 10.5 million fatalities annually, including 20.3% of male fatalities and 16.9% of female fatalities.[1] Established risk factors for coronary artery disease (CAD) include aging, male sex, hypertension, diabetes mellitus, dyslipidemia, and smoking.[2] As the variations observed in the incidence and mortality rates of cardiovascular disease are not fully explained by these factors, there is a need to explore additional markers that could better identify individuals at risk for CAD.

Urinary albumin excretion (UAE) has gained attention as a potential risk marker for CAD.[3] Cardiovascular morbidity and mortality have been observed to be higher in individuals with diabetes, hypertension, and who experience microalbuminuria.[4,5,6] However, there remains a significant amount to uncover regarding the role of microalbuminuria in individuals without diabetes.

Studies have demonstrated that microalbuminuria can predict the onset of ischemic cardiovascular events and is commonly observed in people with cardiovascular disease worldwide.[7] However, the relationship between microalbuminuria and IHD in nondiabetic individuals is not as extensively studied as in diabetic populations.

The link between microalbuminuria and CAD is supported by the underlying mechanisms, including endothelial dysfunction, systemic inflammation, and vascular damage.[8] This link is anticipated to be present regardless of whether diabetes is present or absent. Nonetheless, there is a deficiency of data concerning the correlation between urine microalbumin levels and IHD in individuals who do not have diabetes.

Hence, the study aimed to delve into the connection between IHD and urine microalbumin levels in patients without diabetes. Through an examination of the relevance of urine microalbumin in individuals without diabetes, this investigation aims to enhance our comprehension of microalbuminuria’s potential role as a risk indicator for IHD.

METHODOLOGY

The methodology employed in this study was a case–control design to investigate the relationship between nondiabetic patients and IHD. A total of 100 individuals with IHD and 100 individuals without IHD were enrolled in the study. These cases and controls were carefully matched in terms of age, sex, smoking habits, hypertension, and body mass index (BMI). The study spanned 2 years.

Inclusion criteria involved the diagnosis of IHD based on 12-lead electrocardiogram (ECG), exercise treadmill testing, and cardiac enzyme estimation. Exclusion criteria included diabetes, congestive cardiac failure, and certain urine abnormalities.

The process of data collection involved gathering demographic details, and medical histories, and conducting physical examinations. A range of investigations was undertaken, encompassing complete blood counts, fasting blood sugar (FBS) assessments, lipid profiles, serum creatinine measurements, and urine microalbumin analysis. In addition, 12-lead ECG, treadmill testing, and cardiac enzyme estimation were conducted. Further evaluations were done if indicated, including additional blood tests, renal and liver function tests, serum protein analyses, stool examinations, urine microscopy, and imaging studies.

This methodology aimed to gather comprehensive data from nondiabetic patients with and without IHD to examine the correlation between urine microalbumin and IHD. The study design and investigations were carefully selected to obtain relevant and meaningful results.

Statistical analysis

The statistical analysis was performed using Statistical Package for the Social Science, version 20, (IBM., and Armonk, New York). For data that did not have a normal distribution, continuous variables were either reported as a mean with a standard deviation (SD) or as a median with an interquartile range. Presented as frequencies and corresponding percentages were the categorical variables. A Student’s t-test was used to evaluate group differences for normally distributed continuous variables. Depending on the circumstances, either the Chi-squared test or Fischer’s exact test was used for nominal categorical data. In situations involving nonnormally distributed continuous variables, comparisons were conducted using the Mann–Whitney U test.

In all the performed tests, P < 0.05 was regarded as statistically significant. Signifying a notable distinction between the compared groups. This statistical approach allowed for the comparison of different variables and the determination of significant differences in the study population.

RESULTS

The case and control groups, each comprising 100 individuals, were compared for mean age and gender distribution. No statistically significant difference in mean age (case: 54.7 ± 9.5 years; control: 54.9 ± 10.8 years, P = 0.9) or gender distribution (case: 53 males and 47 females; control: 51 males and 49 females, P = 0.77) was observed. However, a statistically significant difference in BMI was found [case: 24.0 ± 2.7 kg/m²; control: 25.0 ± 4.0 kg/m²; P = 0.04, Table 1].

Table 1.

Baseline characteristics-cases and controls

Characteristics	Case (n=100)	Control (n=100)	P
Mean age (years)	54.7±10.8	54.9±10.8	0.9
BMI (kg/m2)	24.0±2.7	25.0±4.0	0.04*
Male	53	51	0.77
Female	47	49

Mean±Standard Deviation, *Significant

Among the cases (n = 100), 66 individuals had a history of tobacco use, while in the control group (n = 100), 31 individuals reported the same. Those with a history of tobacco use had 4.32 times higher odds of being in the case group compared to the control group (odds ratio [OR] =4.32, 95% confidence interval [CI] =2.3–7.8, P < 0.0001). Similarly, a history of alcohol consumption (cases: 38 and controls: 23) showed a significant association with the case group (OR = 2.05, 95% CI = 1.1–3.8, P = 0.022). Furthermore, a family history of IHD was associated with the case group [cases: 39, controls: 14, OR = 3.9, 95% CI = 1.9–7.8, P < 0.0001, Table 2].

Table 2.

Distribution of Tobacco, history of alcohol and family history of ischemic heart disease in case control group

	Case (n=100)	Control (n=100)	Total	OR	95% CI	P
H/o Tobacco
Present	66	31	97	4.32	2.3-7.8	<0.0001*
Absent	34	69	103
H/o Alcohol
Present	38	23	61	2.05	1.1-3.8	0.022*
Absent	62	77	139
Family H/o IHD
Present	39	14	53	3.9	1.9-7.8	<0.001*
Absent	61	86	147

Mean±Standard Deviation, *Significant

The comparison of heart rate between the case group (n = 100, mean = 87.1 bpm, SD = 14.7) and control group (n = 100, mean = 90.7 bpm, SD = 10.9) did not yield a statistically significant difference (t = −1.9, P = 0.05*). Likewise, there were no noteworthy differences noted in systolic blood pressure (SBP) among the individuals in the case group (mean = 128.7 mmHg, SD = 3.9) and control group (mean = 129.2 mmHg, SD = 5.7; t = −0.75, P = 0.44). However, diastolic blood pressure (DBP) and mean arterial pressure (MAP) exhibited notable variations. The case group had significantly lower DBP (mean = 84.8 mmHg, SD = 7.3) compared to the control group (mean = 90.5 mmHg, SD = 10.0, t = −4.5, P < 0.001*), as well as lower MAP (mean = 99.5 mmHg, SD = 5.1) compared to the control group (mean = 103.3 mmHg, SD = 6.9; t = −4.4, P < 0.001*). In addition, FBS levels were significantly higher in the case group (mean = 107 mg/dL, SD = 13.1) compared to the control group (mean = 99 mg/dL, SD = 17.1; t = 3.71, P < 0.001*).

In summary, heart rate and SBP did not differ significantly, while DBP, MAP, and FBS levels exhibited significant differences between the case and control groups [Table 3].

Table 3.

Comparison of CVS Parameters among different study groups

Characteristics	Case (n=100)	Control (n=100)	t-test	P
Heart Rate	87.1±14.7	90.7±10.9	1.9	0.05*
SBP (mmhg)	128.7±3.9	129.2±5.7	-0.75	0.44*
DBP (mmhg)	84.8±7.3	90.5±10.0	-4.5	<0.001*
Mean Arterial Pressure MAP	99.5±5.1	103.3±6.9	-4.4	<0.001*
FBS level	107±13.1	99±17.1	3.71	<0.001*

Mean±Standard Deviation, *Significant

In this investigation, the lipid profile of the case and control groups was analyzed, encompassing levels of cholesterol, triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The case group (n = 100) displayed a significant increase in cholesterol levels (mean = 177.00 mg/dL, SD = 40.02) compared to the control group (n = 100) which exhibited a mean of 152.02 mg/dL (SD = 32.02) (t = 4.8, P < 0.001*). Conversely, no significant difference was observed in TG levels between the case group (mean = 108.73 mg/dL, SD = 44.25) and the control group (mean = 101.06 mg/dL, SD = 37.31) (t = 1.3, P = 0.18). Similarly, HDL levels showed no substantial difference between the case group (mean = 38.65 mg/dL, SD = 10.75) and the control group (mean = 38.02 mg/dL, SD = 9.98) (t = 0.42, P = 0.66). In contrast, the case group had considerably higher LDL levels (mean = 116.99 mg/dL, SD = 37.03) than the control group (mean = 93.14 mg/dL, SD = 26.55) (t = 5.2, P < 0.001*). The observed differences in cholesterol and LDL levels imply a probable association between the case group and the investigated condition as potential risk factors. The present investigation highlights the importance of assessing lipid profiles in relation to the study of the aforementioned condition [Table 4].

Table 4.

Comparison of lipid profile among different study groups

Lipid profile (mg/dL)	Case (n=100)	Control (n=100)	t-test	P
Cholesterol	177.00±40.02	152.02±32.02	4.8	<0.001*
TG	108.73±44.25	101.06±37.31	1.3	0.18
HDL	38.65±10.75	38.02±9.98	0.42	0.66
LDL	116.99±37.03	93.14±26.55	5.2	<0.001*

*Significant. Mean±SD. SD: Standard deviation, TG: Triglycerides, HDL: High-density lipoprotein, LDL: Low-density lipoprotein

Gender distribution analysis revealed that the case group comprised 24 (46.20%) females and 28 (53.80%) males, while the control group included 2 (40.00%) females and 3 (60.00%) males. The Chi-square test indicated no significant difference in gender distribution (χ² = 0.06, P = 0.49) between the groups.

Regarding tobacco use, 34 (65.40%) individuals in the case group reported tobacco use compared to only 1 (20.00%) individual in the control group. The Chi-square test showed a significant difference in the prevalence of tobacco use between the groups (χ² = 3.96, P = 0.04*).

Similarly, the case group exhibited a higher prevalence of alcohol use, with 20 (38.50%) individuals reporting alcohol use, while none (0.00%) reported it in the control group. The Chi-square test confirmed a significant difference in alcohol use (χ² = 8.29, P = 0.003*) between the case and control groups.

Furthermore, a substantial disparity in the occurrence of a family history of stroke was identified between the case and control groups. Among the cases, 26 (50.00%) individuals reported a family history of stroke, whereas none (0.00%) reported such a history in the control group. The application of the Chi-square test indicated a marked distinction (χ² = 13.13, P = 0.0029*) in the prevalence of a family history of stroke between the two groups [Table 5].

Table 5.

Distribution of gender, tobacco use, alcohol use, and stroke patients in case and control group patients with microalbuminuria

	Case, n (%)	Control, n (%)	χ 2	P
Gender
Female	24 (46.20)	2 (40.00)	0.06	0.49
Male	28 (53.80)	3 (60.00)
Total	52 (100.00)	5 (100.00)
Tobacco use
Present	34 (65.40)	1 (20.00)	3.96	0.04*
Absent	18 (34.60)	4 (80.00)
Total	52 (100.00)	5 (100.00)
Alcohol use
Present	20 (38.50)	0	8.29	0.003*
Absent	32 (61.50)	5 (100.00)
Total	52 (100.00)	5 (100.00)
Family history of stroke
Present	26 (50.00)	0	13.13	0.0029*
Absent	26 (50.00)	5 (100.00)
Total	52 (100.00)	5 (100.00)

*Significant. Mean±SD. SD: Standard deviation

DISCUSSION

The purpose of the study was to investigate the relationship between IHD in people without diabetes and microalbuminuria. The research encompassed a cohort of 100 cases and 100 controls, all sourced from the Department of Medicine at Saraswathi Institute of Medical Sciences. The principal outcomes and deductions from the study are outlined below.

Microalbuminuria, characterized by slightly elevated but abnormal levels of albumin in urine, is recognized as an initial indicator of nephropathy. This condition acts as a noteworthy marker, signifying substantially escalated cardiovascular risk, particularly among individuals with hypertension or diabetes mellitus.

The study concentrated on individuals without diabetes and established a noteworthy correlation between microalbuminuria and IHD. The occurrence of microalbuminuria was found to be more prevalent in nondiabetic patients with IHD in comparison to the overall population. For instance, in a cross-sectional investigation conducted by Hashim et al. in Pakistan, involving 100 nondiabetic patients with IHD, a prevalence of 37% for microalbuminuria was identified using the standard cutoff value of 30 mg/g.[9]

The study’s findings were compared with previous research by Arnlöv et al. showing that microalbuminuria is a reliable biomarker for cardiovascular risk independent of pretest likelihood.[10]

The study found that microalbuminuria was more commonly seen in nondiabetic subjects with elevated levels of cholesterol, TGs, LDL, and serum creatinine compared to the control group. Naha et al. conducted a case–control study on IHD. They found that patients with IHD had significantly higher mean levels of fasting glucose, LDL cholesterol, and urine microalbumin compared to controls.[11] Urine microalbumin, in particular, showed a strong independent association with IHD, and levels >12.6 mg/g were predictive of the disease, with an OR of 13.5 and 95% CI of 4.6–39.9.[11] Similar results to those of Khot et al. were found in that 26% of the patients had hypertriglyceridemia, and 28% had low HDL values (39.6% of females and 34.1% of males had abnormal lipid parameters).[12]

This study shows that microalbuminuria is a significant developing risk factor for CAD and is more common in nondiabetic patients with CAD than in the general population. Similar to our finding, Kumar Jha et al. reported 31.1% of participants with elevated microalbuminuria.[13]

The study highlighted sex differences in microalbuminuria, with males having higher mean albumin levels than females with microalbuminuria. The findings that microalbuminuria is more common in men and that it is age-dependent are in line with other studies by Metcalf et al., Gould et al., and study by Cirillo et al.[14,15,16]

Smoking was recognized as a notable risk factor, contributing to the emergence of both microalbuminuria and IHD. Smoking history was found to be higher among study participants with microalbuminuria. In their study, Khot et al. discovered that smoking was a risk factor that was present in 76.9% of males and 36.3% of females.[12,17]

According to the study conducted by Cirillo et al., UAE and the occurrence of microalbuminuria exhibit robust associations with several factors, which encompass blood pressure, plasma cholesterol levels, smoking, and BMI. When factoring in multiple variables, the relative risks for microalbuminuria were determined to be 2.51 for men and 1.62 for women, with each 18 mmHg increase in SBP. In addition, the relative risks were 2.25 for men and 2.10 for women, corresponding to every 1.0-mmol/L (40 mg/dL) elevation in plasma cholesterol level. Furthermore, the relative risks were 1.99 for men and 1.91 for women in the case of smokers compared to nonsmokers. Similar associations were found for microalbuminuria, defined as a glomerular filtration rate of at least 25 µg/dL for urine albumin excretion.[16] The study suggested the need to reevaluate the threshold defining “pathological” albuminuria, considering the correlation between high levels of normal albuminuria and cardiovascular risk factors which are similar with the finding of the study by Hillege et al.[18]

Overall, the study contributes to the understanding of microalbuminuria as a relevant marker for cardiovascular risk, especially in nondiabetic individuals with IHD. The findings emphasize the importance of early detection and risk assessment to prevent cardiovascular complications in this population.

CONCLUSION

Microalbuminuria is linked to a heightened risk of experiencing cardiovascular disease and cardiovascular-related morbidity. This connection extends beyond the general population, encompassing individuals without diabetes or hypertension as well. Among middle-aged nondiabetic individuals, the presence of microalbuminuria is independently correlated with major cardiovascular risk factors. The study concludes that even mild albuminuria, which is considered within normal ranges, is strongly associated with excessive alcohol and cigarette use. Lifestyle factors have an important role in cardiovascular disease risk.

The study also reveals that men are more likely than women to have microalbuminuria, suggesting that differences in albumin excretion rates may contribute to sex differences in cardiovascular risk. Based on these findings, the study suggests that measuring urine albumin levels could be a useful tool for identifying cardiovascular disease risk factors at an early stage. By identifying individuals at risk, preventive measures can be taken to reduce the incidence of cardiovascular disease in the general population.

This research underscores the significance of microalbuminuria as a potential marker for cardiovascular disease risk and highlights the significance of addressing modifiable risk factors such as alcohol and cigarette use in preventing cardiovascular morbidity and mortality.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.