Renal insufficiency, mortality and myocardial infarction

Background: Patients with dialysis-dependent renal insufficiency (RI) have a markedly increased risk of dying or developing cardiovascular disease. Among patients who have coronary heart disease (CHD), moderate or severe RI is associated with increased mortality. In the general population the association between mild or moderate RI and long-term risk of death or myocardial infarction (MI) is not well described.

Aims: To study the associations between mild, moderate or severe RI and death or MI among individuals with or without CHD. To investigate the importance of dyslipidemia, in particular the apolipoprotein (apo) B/apoA-1 ratio, in relation to MI among individuals with or without chronic kidney disease (CKD).

Methods and Results: In 6,711 patients undergoing coronary artery bypass grafting (CABG), already moderate RI was associated with mortality within 30 days of CABG (Odds ratio (OR) 1.4, (95% Confidence Interval (CI), 1.2 to 4.8) (Study I). Among those patients who survived 30 days post-operatively, the association between RI and incidence of MI and all-cause mortality within five years of CABG was investigated (Study II). All-cause mortality was associated with mild, moderate and severe RI; hazard ratio (HR) (and 95% CI) 1.2 (1.0 to 1.6), HR 1.8 (1.3 to 2.4) and HR 5.2 (3.1 to 8.6), respectively. Patients with moderate or severe RI had an increased incidence of MI. In 571,353 mainly healthy individuals from the AMORIS cohort, glomerular filtration rates were estimated using the Modification of Diet in Renal Disease study equation (GFRMDRD) and the Mayo formula (GFRMayo) and related to all-cause mortality and incidence of MI (Study III). During 11.6 years of follow-up hazard ratios for MI, using GFRMayo were 1.11 (1.06 to 1.16) for mild, 1.32 (1.18 to 1.48) for moderate and 2.54 (1.90 to 3.40) for severe RI. Similar associations were found for allcause mortality. Using GFRMDRD the association between RI and adverse outcomes was weaker. In 142,394 individuals from the AMORIS cohort, the apoB/apoA-1 ratio and standard lipid measures, were evaluated as predictors of first MI in relation to presence or absence of CKD defined as GFRMDRD 15-60 mL/min/1.73 m2 (Study IV). For those without CKD the adjusted HR for the highest versus the lowest quartile of the apoB/apoA-1 ratio was 2.88 (2.54 to 3.26) compared to HR, 3.35 (2.25 to 4.91) for those with CKD. After adjustment for the total cholesterol/ high-density lipoprotein cholesterol ratio, an increase by one standard deviation of the apoB/apoA-1 ratio was associated with a HR of 1.44 (1.30 to 1.59) for MI, among individuals with CKD.

Conclusions: Renal insufficiency among patients undergoing CABG is related to an increased 30-day mortality, five-year mortality and incidence of MI. Renal insufficiency in the general population is related to an increased long-term incidence of MI and allcause mortality. The apoB/apoA-1 ratio is a strong predictor for MI irrespective of renal function and may add information about risk of future CHD even after adjustment for standard lipid measures. Key words: Renal insufficiency, mortality, myocardial infarction, chronic kidney disease, coronary artery bypass surgery, glomerular filtration rate, apolipoproteins, lipids, general population

List of scientific papers

I. Holzmann MJ, Ahnve S, Hammar N, Jörgensen L, Klerdal K, Pehrsson K, Ivert T (2005). "Creatinine clearance and risk of early mortality in patients undergoing coronary artery bypass grafting." J Thorac Cardiovasc Surg 130(3): 746-52
https://pubmed.ncbi.nlm.nih.gov/16153923

II. Holzmann MJ, Hammar N, Ahnve S, Nordqvist T, Pehrsson K, Ivert T (2007). "Renal insufficiency and long-term mortality and incidence of myocardial infarction in patients undergoing coronary artery bypass grafting." Eur Heart J 28(7): 865-71. Epub 2007 Feb 15
https://pubmed.ncbi.nlm.nih.gov/17303587

III. Holzmann M, Ivert T, Jungner I, Nordqvist T, Walldius G, Östergren J, Hammar N (2008). "Renal function assessed by two different formulas and incidence of myocardial infarction and death." (Submitted)

IV. Holzmann M, Jungner I, Walldius G, Ivert T, Nordqvist T, Östergren J, Hammar N (2008). "Apolipoproteins B and A-1, standard lipid measures and incidence of myocardial infarction in men and women, with or without chronic kidney disease." (Submitted)