Cardiovascular Morbidities in Patients with Diabetes Mellitus and CKD

Chronic kidney disease (CKD) is a major complication among patients with diabetes mellitus. The age-standardized prevalence of diabetic kidney disease (DKD) according to results of a survey from the Global Burden of Disease report was 15 to 16 per 1000. A recent systematic review found that 31.3% of patients with incident end-stage kidney disease (ESKD) had diabetic nephropathy, and the annual incidence of ESKD among diabetic patients increased approximately threefold over 2 decades.

Approximately 20% to 40% of patients with diabetes mellitus have DKD, resulting in a high risk of cardiovascular events. However, the risk and timing of the development of cardiovascular disease may differ depending on their type. According to Chia-Ter Chao, MD, PhD, and colleagues at the National Taiwan University Hospital, Taipei, Taiwan, there are few data available on whether CKD has differing influences on the risk of developing each cardiovascular morbidity in patients with newly diagnosed diabetes mellitus.

The researchers conducted an analysis of data from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort to examine the risk trajectory of developing a wide spectrum of cardiovascular complications, i.e., heart failure, acute myocardial infarction (AMI), peripheral vascular disease (PVD), ischemic stroke (IS), hemorrhagic stroke (HS), and atrial fibrillation. Mortality was also an outcome of interest. Results of the analysis were reported online in Cardiovascular Diabetology [2021;doi.org/10.1186/s12933-021001279-6].

Patients in the LCDP cohort diagnosed with incident diabetes mellitus between 2004 and 2010 were identified. Patients who developed CKD following diabetes diagnosis were matched with counterparts who did not develop CKD. The researchers examined the cardiovascular morbidity-free rates of patients in the two groups (with and without CKD) and conducted Cox proportional hazard regression analyses. The cumulative risk of developing each outcome consecutively during the study period was also assessed. Patients were followed-up until death, the development of any of the cardiovascular morbidities of interest, or the end of the study (December 31, 2011).

The study selection process began with 840,000 patients with diabetes mellitus in the LCDP cohort. Adults with incident diabetes mellitus and adequate follow-up time without any of the cardiovascular morbidities of interest were identified (n=429,616; 51.1%). Of those, 57,304 (13.3%) had CKD. Following 1:1 propensity matching, the final study cohort included 55,961 patients with DKD and 55,961 without DKD.

There were no significant differences between the two groups in demographic profiles, lifestyle factors, year of diabetes mellitus diagnosis, and most comorbidities and medications, with the exception of a modestly increased prevalence of chronic liver disease, gout, and malignancy in the group without DKD. The standard mean deviations of each variable between groups were lower than 0.1, suggesting that the distribution of each variable between groups was balanced.

Following a median of 4.2 years of follow-up, 11% of patients died (n=12,270), and 2.5% (n=2778), 1.1% (n=1250), 0.5% (n=534), 2.6% (n=2914), 0.7% (n=800), and 1.9% (n=2181) developed incident heart failure, AMI, PVD, IS, HS, and atrial fibrillation, respectively. Patients in the DKD group had a significantly higher incidence of developing heart failure (P<.01), AMI (P=.04), and PVD (P<.01), compared with patients in the group without DKD; there was no difference in the incidence of IS and HS between the two groups.

Results of Cox proportional hazard regression demonstrated that patients with diabetes mellitus and incident CKD had a significantly higher risk of morality (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.06-1.14), developing HF (HR, 1.282; 95% CI, 1.19-1.38), AMI (HR, 1.16; 95% CI, 1.04-1.3), and PVD (HR, 1.277; 95% CI, 1.08-1.52), compared with patients without CKD during follow-up. There were no differences in the risk of IS, HS, and atrial fibrillation between the two groups.

In analysis of the odds ratio of mortality and of developing each cardiovascular morbidity of interest annually over 7 years of follow-up within the study period, the risk of each cardiovascular morbidity associated with CKD after incident diabetes mellitus followed different trajectories. The CKD-associated risk of mortality as well as developing HF and AMI became significant soon after the diagnosis of diabetes mellitus, and remained significant throughout the study period. Conversely, the risk of PVD associated with CKD in patients with diabetes mellitus did not emerge until 4 years after diagnosis of diabetes, and the risk of IS, HS, and atrial fibrillation associated with CKD remained insignificant up to 7 years after the initial diabetes diagnosis.

The researchers cited some limitations to the study, including the retrospective analysis of prospectively collected data, using physician discretion for the diagnosis of cardiovascular morbidity, the lack of data on severity of each cardiovascular morbidity, and the inability to analyze the subgroup of patients with advanced CKD. In addition, because the cohort included only diabetic patients of Asian ethnicity, the generalizability of the findings to patients of other ethnicities is unknown.

In conclusion, the researchers said, “Using a population-based cohort of patients with newly diagnosed diabetes, we examined whether the CKD-associated risk of developing cardiovascular diseases differed depending on the disease type and the duration of diabetes mellitus. We were able to show that the risk profile could be divergent; the risk of mortality, heart failure, and AMI introduced by CKD remained significant throughout the follow-up period, while the risk of PVD did not emerge until 4 years after the initial diabetes mellitus diagnosis. On the other hand, among these newly diagnosed diabetes mellitus patients, the CKD-associated risk of IS, HS, and atrial fibrillation was insignificant. These findings are expected to shed light on the optimal strategy for detecting early cardiovascular complications among patients with incident diabetes mellitus, and facilitate the timely administration of cardiovascular care.”

Takeaway Points

1. Researchers in Taiwan conducted a study to determine whether chronic kidney disease (CKD) in newly diagnosed diabetes mellitus differentially influences the risk of developing mortality and six prespecified cardiovascular complications.
2. Patients with incident diabetes mellitus and CKD were matched with patients with incident diabetes without CKD. The risk of mortality, heart failure, and acute myocardial infarction in the group with CKD occurred soon after the diagnosis of diabetes mellitus and remained significant throughout the follow-up.
3. The CKD-associated risk of peripheral vascular disease did not emerge until 4 years later; the CKD-associated risk of ischemic stroke, hemorrhagic stroke, and atrial fibrillation remained insignificant throughout the follow-up period.